Search PubMed⌕ Search

Biomedical subjects

B Weber

Publications and source records attributed to B Weber.

At least 127 records · Page 7Linked to original sources
PubMed1998

Monoamine oxidase B single-photon emission tomography with [123I]Ro 43-0463: imaging in volunteers and patients with temporal lobe epilepsy.

Imaging of monoamine oxidase of subtype B (MAO B) is of interest in various neurological diseases. In the past non-invasive assessment of MAO B has only been possible with positron emission tomography (PET) ligands. Given the limited availability of PET, a single-photon emission tomography (SPET) ligand would be desirable. In this study SPET imaging with the new MAO B inhibitor [123I]Ro 43-0463 was performed in five volunteers and nine patients with temporal lobe epilepsy (TLE). In two volunteers a second study was performed 12 h following blockade with deprenyl. In the TLE patients the tracer was administered as bolus (n = 4) or as prolonged infusion (n = 5). The regional uptake pattern correlated well with the known distribution of MAO B. In the two blocking studies ligand uptake was substantially reduced compared with baseline. In the TLE patients increased uptake was found in the ipsilateral mesial temporal lobe and, surprisingly, in the ipsilateral putamen. This study indicates the potential of the new SPET ligand [123I]Ro 43-0463 to map MAO B concentration in the human brain. The new finding of increased MAO B in the putamen of TLE patients needs further studies to elucidate its exact pathophysiology.

Adult↗
PubMed1998

Does the long-term clinical course of type I diabetes mellitus differ in patients with prepubertal and pubertal onset? Results of the Berlin Retinopathy Study.

UNLABELLED: The objective of the present study was to investigate potential differences at presentation of type I diabetes and during its long-term clinical course in children and adolescents with prepubertal and pubertal manifestation. Clinical, immunological and biochemical characteristics at diabetes onset of 453 patients (320 prepubertal, 133 pubertal; median age at manifestation 7.1 years (0.7-13.9) and 13.1 years (9.2-17.6), respectively) were evaluated. Glycaemic control and exogenous insulin requirements were followed prospectively, with a median follow up of 9.4 years. At the onset of the disease no differences concerning the degree of metabolic decompensation, impairment of somatic health, and islet cell antibody status could be detected between the groups, except for a smaller body weight loss in pubertal patients (P=0.011). The duration of partial remission (insulin requirements <0.5 IU/kg body weight/day) was unrelated to age or pubertal status at onset. It was found to be longer in boys than in girls in the total cohort (median duration: 279 vs 215 days, P = 0.0071). Despite an absence of differences during the early course of the disease, glycaemic control was better, and daily insulin doses were significantly lower in patients with pubertal onset, after 6 years of diabetes. CONCLUSION: Adolescents with a pubertal onset of type I diabetes have a more benign long-term course of the disease demonstrating better glycaemic control and lower insulin requirements, although the presentation of the disease at onset and its course during the first 6 years are not different from those of children with a prepubertal manifestation of diabetes.

Adolescent↗
PubMed1998

Expression of hypoxia-inducible genes in tumor cells.

Tumor tissue oxygenation impacts on proliferation of cancer cells and their sensitivity towards radio- and chemotherapy. Under low oxygen, mammalian cells show an adaptive response that leads to the induction of a number of genes with well-defined roles in oxygen supply and energy maintenance, e.g. genes encoding enzymes of the glycolytic pathway. The hypoxia-inducible factor 1 (HIF-1), a transcription factor consisting of the two proteins HIF-1alpha and HIF-1beta, plays a major role in the pleiotropic response observed under low oxygen. We have determined, by Northern analysis, the mRNA levels of HIF-1alpha and of two glycolytic enzymes known to be transcriptionally activated by HIF-1, namely phosphoglycerate kinase 1 (PGK 1) and pyruvate kinase M2 (PKM2), in different hepatoma cell lines and in mouse and human tissues. Hypoxic treatment of various mouse and human hepatoma cell lines led to the expected increase in the amount of PGK1 and PKM2 mRNA, while HIF-1alpha mRNA levels were not significantly elevated. Analysis of mouse liver tumors demonstrated no tumor-specific increases in HIF-1alpha or PGK1 mRNA levels. In five of eight human colorectal cancers investigated, PGK1 and PKM2 mRNA levels were increased in comparison to the corresponding normal tissues, while HIF-1alpha mRNA levels were not significantly changed. The majority of the colorectal cancers demonstrated p53 immunoreactivity, presumably due to mutation of the gene; there was, however, no correlation between the p53 staining pattern and mRNA expression levels of glycolytic enzymes.

Animals↗
PubMed1998

Reduction of the diagnostic window with a new combined p24 antigen and human immunodeficiency virus antibody screening assay.

In order to reduce the window phase between time of human immunodeficiency virus (HIV) infection and laboratory diagnosis, new fourth generation screening assays which permit a simultaneous detection of HIV antigen and antibody have been developed. In a multicenter study, a new automated fourth generation assay, Enzymun-Test HIV Combi (Boehringer Mannheim GmbH) was compared to third generation assay, p24 antigen tests and Western blot. A total of 37 seroconversion panels, samples of the early infection (n = 42), HIV-1 antibody positive sera, including subtypes A E, and O (n = 1118), HIV-2 positive samples (n = 252) and cell culture supernatants infected with different HIV-1 subtypes and HIV-2 (n = 50), blood donors (n = 6649), hospitalized patients (n = 475), HIV neg. sera with indeterminate Western blot (n = 32), potentially cross reactive serum samples (n = 435) and HIV negative specimens from Cameroon (n = 68) were tested. A total of 16 of 29 seroconversions were detected on average 8.5 days earlier with Enzymun-Test HIV Combi than HIV-1/HIV-2 3rd generation EIA (Abbott Laboratories). Overall, in the 29 panels investigated comparatively with the two assays, the mean time delay between Enzymun-Test HIV Combi and HIV-1/HIV-2 3rd generation EIA was 4.7 days. HIV antigen was detected in three out of 35 seroconversions one bleed earlier with HIV-1 Ag Monoclonal than with Enzymun-Test HIV Combi. Enzymun-Test HIV Combi showed a sensitivity of 100% for HIV antibody detection for HIV-1 group M and O and HIV-2 positive specimens. While p24 antigen of different HIV-1 subtypes was detected with Enzymun-Test HIV Combi in all the 49 cell culture supernatants, HIV Ag was not detected in an HIV-2 virus lysate. A total of 66 false positive results out of 7659 HIV negative samples were obtained with the Enzymun-Test HIV Combi. The specificity for unselected blood donors was 99.6%. The Enzymun-Test HIV Combi permits an earlier diagnosis of HIV infection than third generation assays through the detection of p24 antigen, which may be present in serum samples from individuals with recent HIV infection prior to seroconversion and it shows an excellent sensitivity for antibodies to all known HIV-1 subtypes and HIV-2. The specificity in blood donors and hospitalized patients is comparable to that of other assays.

HIV Antibodies↗
PubMed1998

Identification of a common mutation (R245H) in Sanfilippo A patients from The Netherlands.

We have identified a common mutation (R245H) in the sulphamidase gene of Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA, MPS IIIA) patients from The Netherlands. Allele-specific oligonucleotide hybridization was used to determine the incidence of this mutation in 45 unrelated MPS IIIA patients from different regions of The Netherlands. R245H was present in 51 alleles, representing 56.7% of the total allelic population. Of 39 patients, for whom we have uniform clinical details, 13 MPS IIIA patients who were homozygous for this common mutation had a more uniform but severe clinical phenotype than the remaining 21 or 5 patients, containing respectively one or no R245H alleles. The R245H allele had a higher prevalence in western rather than eastern regions of The Netherlands.

Adolescent↗
PubMed1998

Efficacy and safety of the paclitaxel and carboplatin combination in patients with previously treated advanced ovarian carcinoma. A multicenter GINECO (Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens) phase II study.

BACKGROUND: Platinum compounds are the most active drugs in ovarian cancer treatment; cisplatin and carboplatin demonstrated similar efficacies but different toxicity profiles. Paclitaxel combined with cisplatin as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated than cisplatin-paclitaxel. DESIGN: The objective of the present study was to assess the efficacy and safety of the combination of paclitaxel and carboplatin in previously treated advanced ovarian cancer patients. PATIENTS AND METHODS: During or after platinum-based chemotherapy, 73 patients with progressive advanced epithelial ovarian carcinoma were enrolled to receive every four weeks a three-hour infusion of paclitaxel 175 mg/m2 followed by a 30-minute carboplatin infusion. The carboplatin dose was calculated to obtain the recommended area concentration-versus-time under the curve of 5 mg x ml-1 x min. RESULTS: Toxicity and response could be evaluated for 72 and 62 patients, respectively. Eleven complete and 15 partial responses gave an overall response rate of 42% (95% CI: 30%-54%). Response rates for platinum-refractory patients and those with early (> or = 3 and < 12 months) and late (> 12 months) relapses were 24%, 33% and 70%, respectively. The respective median response duration, the median progression-free survival and median overall survival were 8, 6 and 14 months. Myelosuppression was the most frequent and severe toxicity. Grade 3 and 4 neutropenia occurred, respectively in 30% and 23% of the cycles; 6% of the cycles benefited from medullary growth factors. Only one episode of febrile neutropenia was observed. Grade 3 and 4 thrombocytopenia occurred, respectively during 3% and 1% of the cycles. Alopecia was frequent. Transient peripheral neuropathy developed in 47% of patients but was severe in only one patient. One early death was attributed to progressive disease and possibly to therapy. CONCLUSION: This combined paclitaxel-carboplatin therapy is effective and can be safely administered to ovarian cancer patients who relapse after one or two regimens of platinum-based chemotherapy.

Adolescent↗
PubMed1998

Presence and distribution of hyaluronan in human corneas after phototherapeutic keratectomy.

PURPOSE: To evaluate the reactive hyaluronan (HA) formation in the human cornea following excimer laser surgery. METHODS: Fourteen patients underwent phototherapeutic keratectomy in order to remove corneal opacifications caused by a range of diseases. A penetrating corneal transplantation was performed between 6 and 44 months later because of unsatisfactory visual outcome. The corneal buttons were fixed in 4% formaldehyde containing 1% cetylpyridine chloride. The histological sections were stained for the presence of hyaluronan. RESULTS: Hyaluronan was found in the subepithelial region of the ablated area in thirteen out of fourteen human corneal specimens It was present as long as 44 months after surgery and it is found despite of topical steroid treatment postoperatively. CONCLUSION: The human cornea commonly reacts to excimer laser surgery by the formation of hyaluronan.

Adult↗
PubMed1998

Dreaming and insomnia: dream recall and dream content of patients with insomnia.

The present study investigated dream recall frequency and dream content of patients with insomnia in comparison to healthy controls. Patients' dream recall frequency was elevated, due mainly to their heightened frequency of nocturnal awakenings. Dream content seems to reflect waking life stressors found in these patients, i.e. dream emotions were more negative and dreams were characterized by themes of depression, 'negatives' in self-description and health themes. Patients taking antidepressants showed lower dream recall frequency than patients without any medication; benzodiazepine intake, however, did not affect dream recall frequency. Both drug groups reported more positively toned dreams than drug-free patients. It is suggested that future studies should use more dreams per subject in order to reduce error variance of the dream content measures and more detailed measures of waking life stress.

Adult↗
PubMed1998

Endurance training and its effect upon the activity of the GH-IGFs system in the elderly.

There is an age-associated decline in the activity of the GH-IGFs system. However, so far, it has not been studied, whether this decline in somatotrophic activity might be preventable by intensive exercising. We studied 11 elderly male (50-78 years) marathon runners and 10 age-matched male (52-73 years) sedentary controls to evaluate plasma concentrations of GH, total and free IGF-I and IGF-II and of IGF-binding protein-1 (IGFBP-1), IGFBP-2, IGFBP-3 and insulin. When comparing the two groups (runners vs controls) no differences were found in GH (1.0 +/- 1.2 vs 1.3 +/- 1.3 microg/l [mean +/- SD]), IGF-1 (115 +/- 23 vs 113 +/- 21 microg/l), IGF-II (961 +/- 192 vs 864 +/- 125 microg/l), free IGF-1 (227 +/- 80 vs 318 +/- 146 ng/l), free IGF-II (563 +/- 249 vs 492 +/- 108 ng/l), IGFBP-3 (2403 +/- 515 vs 2307 +/- 326 microg/l) or insulin (26 +/- 13 vs 27 +/- 18 mU/l). However, IGFBP-1 (4.44 +/- 2.61 vs 2.28 +/- 0.93 microg/l) and IGFBP-2 (493 +/- 143 vs 340 +/- 186 microg/l) were found to be significantly increased in marathon runners. In conclusion, our findings do not support the hypothesis that the age-associated decline in GH, IGF-1 and IGFBP-3 may be preventable by intensive endurance training. However, marathon running affects the regulation of the GH-IGFs system activity at the level of IGFBP-1 and -BP-2.

Aged↗
PubMed1998

Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.

The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.

Adult↗
PubMed1998

Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study.

Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P<.001), although only 8% of the variance in age at diagnosis could be explained by the specific mutation, and there was no evidence of family-specific effects. When the age at diagnosis of the breast cancer cases was examined by OCCR, cases associated with mutations in the OCCR had a significantly older mean age at diagnosis than was seen in those outside this region (48 years vs. 42 years; P=.0005).

Adult↗
PubMed1998

Changes of cerebral blood flow during short-term exposure to normobaric hypoxia.

Decreased arterial partial oxygen pressure (PaO2) below a certain level presents a strong stimulus for increasing cerebral blood flow. Although several field studies examined the time course of global cerebral blood flow (gCBF) changes during hypoxia at high altitude, little was known about the regional differences in the flow pattern. Positron emission tomography (PET) with [(15)O]H2O was used on eight healthy volunteers to assess regional cerebral blood flow (rCBF) during short-term exposure to hypoxia corresponding to simulated altitudes of 3,000 and 4,500 m. Scans at the simulated altitudes were preceded and followed by baseline scans at the altitude of Zurich (450 m, baseline-1 and baseline-2). Each altitude stage lasted 20 minutes. From baseline to 4,500 m, gCBF increased from 34.4 +/- 5.9 to 41.6 +/- 9.0 mL x minute(-1) x 100 g(-1) (mean +/- SD), whereas no significant change was noted at 3,000 m. During baseline-2 the flow values returned to those of baseline-1. Statistical parametric mapping identified the hypothalamus as the only region with excessively increased blood flow at 4,500 m (+32.8% +/- 21.9% relative to baseline-1). The corresponding value for the thalamus, the structure with the second largest increase, was 19.2% +/- 16.3%. Compared with the rest of the brain, an excessive increase of blood flow during acute exposure to hypoxia is found in the hypothalamus. The functional implications are at present unclear. Further studies of this finding should elucidate its meaning and especially focus on a potential association with the symptoms of acute mountain sickness.

Adult↗
PubMed1998

Neuronal complexity loss in interictal EEG recorded with foramen ovale electrodes predicts side of primary epileptogenic area in temporal lobe epilepsy: a replication study.

PURPOSE: To investigate whether a correct lateralization of the primary epileptogenic area by means of neuronal complexity loss analysis can be obtained from interictal EEG recordings using semi-invasive foramen ovale electrodes. In a previous study with recordings from intrahippocampal depth and subdural strip electrodes it was shown that the dynamics of the primary epileptogenic area can be characterized by an increased loss of neuronal complexity in patients with unilateral temporal lobe epilepsy (TLE). METHODS: Neuronal complexity loss analysis was applied. This analysis method is derived from the theory of nonlinear dynamics and provides a topological diagnosis even in cases where no actual seizure activity can be recorded. We examined interictal EEG recorded intracranially from multipolar foramen ovale electrodes in 19 patients with unilateral TLE undergoing presurgical evaluation. RESULTS: The primary epileptogenic area was correctly lateralized in 16 of the 19 investigated patients. The misclassification of the side of seizure onset in three patients might be attributed to the larger distance between the foramen ovale electrodes and the mesial temporal structures as compared to intrahippocampal depth electrodes. CONCLUSIONS: Our results confirm the previous findings and provide further evidence for the usefulness of nonlinear time-series analysis for the characterization of the spatiotemporal dynamics of the primary epileptogenic area in mesial temporal lobe epilepsy.

Adult↗
PubMed1998

Computerized self-assessment in psychiatric in-patients: acceptability, feasibility and influence of computer attitude.

In recent years various approaches using computerized assessments and tests in psychiatry have been published. In our study, the acceptability and feasibility of computerized self-assessments and attitude to computers were examined in psychiatric in-patients, using an improved interactive schedule, the Interactive Self-Assessment Scale (ISAS), based on the Windows operating system. In general we found a good level of acceptability and feasibility of the computerized self-assessment. Our results confirm the influence of attitude to computers on acceptability, and indicate a lack of self-confidence in interacting with computers, accompanied by a less positive attitude to computers than reported by healthy subjects and psychiatric out-patients. Computerized self-assessment is suitable for psychiatric in-patients. Nevertheless, further research is necessary in order to improve attitude to computers and the patient-computer interaction.

Adult↗
PubMed1998

Effects of testosterone suppression on serum levels of hepatitis B surface antigen and HBV-DNA in men.

AIMS/BACKGROUND: There is epidemiological evidence that progression of hepatitis B virus (HBV)-induced liver disease is adversely influenced by male gender. Furthermore, in male transgenic mice, HBsAg levels increase after puberty, resulting in 4- to 10-fold higher HBsAg levels than in female transgenic mice. Castration reduces HBsAg levels by 90-95%, while substitution of testosterone to castrated animals rapidly increases HBsAg concentrations. We hypothesized that suppression of endogenous testosterone levels may have similar effects on HBsAg serum levels in men, as observed in male mice. METHODS: To test our hypothesis, we studied the influence of reversible testosterone suppression by the LHRH-analog triptorelin on serum concentrations of HBsAg and HBV-DNA. Eight male patients, who were chronically infected with HBV, were studied in a prospective interventional study. RESULTS: Triptorelin decreased serum testosterone levels to castration levels for several weeks. However, this reversible testosterone suppression had no effect on HBsAg or HBV-DNA serum concentrations (p > 0.05). CONCLUSIONS: Suppression of endogenous testosterone levels had no effect on HBsAg levels in men, which points to a different regulation of HBsAg expression in men compared with transgenic mice.

Adult↗
PubMed1998

Multicenter evaluation of the new automated Enzymun-Test Anti-HIV 1 + 2 + subtyp O.

An international multicenter study was performed to evaluate a new, automated human immunodeficiency virus (HIV) third-generation antibody assay. The Enzymun-Test Anti-HIV 1 + 2 + Subtyp O showed 100% sensitivity and 99.8% specificity among 11,172 samples from hospitalized patients and blood donors. For early HIV antibody detection in seroconversion panels, Enzymun-Test showed a sensitivity equivalent to that of the Abbott Recomb. HIV-1/HIV-2 3rd Gen. assay.

Automation↗