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Biomedical subjects

W Vogel

Publications and source records attributed to W Vogel.

At least 109 records · Page 6Linked to original sources
PubMed1999

Duodenal metal-transporter (DMT-1, NRAMP-2) expression in patients with hereditary haemochromatosis.

BACKGROUND: Although the gene for hereditary haemochromatosis has been cloned, the mechanism by which iron uptake is inappropriately increased in this disorder is unclear. Iron absorption is regulated by the duodenal metal transporter, DMT-1, also called NRAMP-2. We investigated the expression of NRAMP-2 in patients with hereditary haemochromatosis. METHODS: Duodenal biopsy samples were taken from 20 patients with haemochromatosis homozygous for the C282Y mutation and from ten controls. NRAMP-2 expression was assessed by northern blotting and competitive PCR. NRAMP-2 mRNA was sequenced in seven patients and two controls. FINDINGS: Duodenal NRAMP-2 mRNA concentrations were increased in patients as estimated by Northern blotting. Accordingly, competitive PCR showed significantly higher NRAMP-2 cDNA concentrations in patients than in controls (mean 3.43 [SD 0.61] vs 1.11 [0.74] log ng competitor x 10(4); p<0.001). No mutations were found within the NRAMP-2 mRNA. Duodenal NRAMP-2 mRNA expression was correlated with serum ferritin in controls (r=-0.94, p=0.001) but not in patients (r=-0.18, p=0.8). INTERPRETATION: Increased NRAMP-2 mRNA expression in duodenal mucosa of patients with hereditary haemochromatosis may promote duodenal iron uptake and lead to iron overload.

Adult↗
PubMed1999

Detailed marker chromosome analysis in cell line U-BLC1, established from transitional-cell carcinoma of the bladder.

A permanent cell line, U-BLC1, was established from a primary transitional-cell carcinoma, TCC, of the urinary bladder. Karyotype analysis showed the line to be highly aberrant, with a near-triploid chromosome number of 68 to 73. Comparative genomic hybridization revealed some distinct differences between the primary tumor and the established cell line. Karyotype analysis showed 3 marker chromosomes with homogeneously staining regions, HSRs, in the cell line. The HSRs were isolated by microdissection and the microdissection probes were hybridized to normal metaphase chromosomes. The HSRs contain sequences known to be frequently involved in amplification in transitional-cell carcinoma of the bladder, 6p22, 7p11-p12, 9p23-pter, and one region not yet reported to be amplified in primary TCC of the bladder, 1p31-p32. A candidate-gene approach showed that in the region 7p11-p12 the EGFR locus is amplified and highly expressed.

Aged↗
PubMed1999

Axonal expression of sodium channels in rat spinal neurones during postnatal development.

1. Postnatal expression of Na+ channels and development of somatic excitability were studied in dorsal horn neurones of rat using patch-clamp recordings from spinal cord slices in combination with the 'entire soma isolation' method. 2. The amplitude of Na+ current in the intact neurone in the slice increased with postnatal development (days 0-39) with a mean rate of 83 pA day-1. 3. The Na+ current in the neuronal soma did not increase with age and the soma, separated from the axon, was not able to fire spikes at any stage of development studied. 4. It is concluded that the postnatal development of the spinal dorsal horn neurone is accompanied by intensive expression of Na+ channels in the axonal but not somatic membrane. The estimated minimum density of Na+ channels in the axon initial segment is approximately 160 channels microm-2.

Animals↗
PubMed1999

Fructose malabsorption is associated with decreased plasma tryptophan.

Fructose malabsorption is characterized by the inability to absorb fructose efficiently. Consequently fructose reaches the colon and is broken down by bacteria to short-fatty-acids, CO2 and H2. Recently we found that fructose malabsorption was associated with signs of depression. It was therefore of interest to find out whether fructose malabsorption is associated with abnormal tryptophan metabolism. Breath hydrogen concentrations were measured in 50 after an oral dose of 50 g fructose allowing to classify them as normals (n = 15) or fructose malabsorbers (n = 35). Blood samples were taken for tryptophan and kynurenine measurements. Fructose malabsorbers showed significantly lower plasma tryptophan concentrations and significantly higher depression scores compared to normals. Fructose malabsorption is associated with lower tryptophan levels which may play a role in the development of depressive disorders.

Adolescent↗
PubMed1999

[The Geriatric Minimum Data Set (Gemidas) of the Federal Association of Clinical Geriatric Facilities e. V. as an instrument for quality assurance in inpatient geriatrics].

BACKGROUND: Geriatric medicine in Germany is faced with an increasing demand for continuous documentation and evaluation of its effectiveness and efficiency. Hence, the Federal Association (FA) of Clinical Geriatric Departments (Bundesarbeitsgemeinschaft der Klinisch-Geriatrischen Einrichtungen e.V.) has funded a working group on improving quality management in geriatrics by developing criteria for quality standards. METHODS: In 1996, the FA working group achieved consensus on the definition of the Geriatric Minimum Data Set (Gemidas) which covered (i) core information about a patient's age, sex, living arrangement, and (ii) basic characteristics of the hospital course such as location prior to admission and past discharge, leading and accompanying diagnoses, newly prescribed technical aids, objective functional status on admission and at discharge (e.g., Barthel Index (BI), Timed Up & Go (TUG), and intensity of professional care (PPR)), as well as subjectively evaluated attainment of treatment goals. This initial report describes the instrument and presents analyses of its feasibility for routine clinical practice and data consistency. RESULTS: Twenty out of 27 hospitals (74%) integrated Gemidas successfully in daily routine, 75% of which (15 hospitals, total n = 10,567 patients) instantaneously collected data on constant numbers of patients per month. Multivariate regression analyses used to decompose variances of the instrument's central indicators (e.g., BI, TUG, PPR) revealed a satisfactory dimensionality and high consistency (e.g., covering 59% of variance in BI with 53% of variance uniquely attributable to patient characteristics), as well as sensitivity to differences between hospitals (e.g., 12% of variance in duration of stay uniquely attributable to hospital differences after controlling for patients' characteristics). CONCLUSION: Gemidas appears to be a feasible quality assurance instrument in geriatrics, suitable for compiling its data into a central registry database, which may then be used for analyses across and between hospitals. However, some modifications are still necessary and more detailed analyses needed, before final recommendations can be made.

Aged↗
PubMed1999

Vitamin D receptor polymorphisms as markers in prostate cancer.

Polymorphisms in the vitamin D receptor (VDR) gene have been analyzed in several studies for an association with prostate cancer (PCA) and odds ratios (OR) > or = 3 have been observed in study populations from North America. We studied three polymorphisms in the VDR gene (poly-A microsatellite, TaqI and FokI RFLPs) in 105 controls and 132 sporadic PCA cases from France and in a collection of families from Germany and France. The polymorphisms near the 3' end of the gene were in linkage disequilibrium with an almost complete coincidence of the short poly-A alleles and t (presence of the restriction site) of the TaqI polymorphism, (contingency tables, P<0.0001). An association was found by logistic regression for the poly-A between PCA and the heterozygous genotype (S/L; S < 17, L > or = 17, OR=0.44, 95% confidence interval, CI=0.198-0.966, P=0.041). OR was lower in patients < or = 70 years old and patients with a Gleason score > or = 6. The Tt genotype of the TaqI RFLP also showed an association with PCA (OR=0.5, CI=0.27-0.92, P=0.026). This association was also stronger for patients < or = 70 years old (OR=0.31, CI=0.15-0.63, P=0.001). The risk alleles were S and t alleles as indicated by the OR of the homozygotes, although these were not significant. The FokI RFLP at the 5' end of the gene did not reveal any association (P>0.7). While some association studies differ between Europe and North America, our present findings with the VDR gene agree with those from North America, indicating a weak but general role of the VDR in PCA susceptibility.

Aged↗
PubMed1999

Child psychiatry in Johannesburg, South Africa. A descriptive account of cases presenting at two clinics in 1997.

The records of all new cases presenting to two child psychiatry clinics (at four locations) in Johannesburg during 1997 have been entered into a database and analyzed to assist in the development of services, to improve clinical practice and to facilitate research. Results are presented for demographic data, referral sources, presenting complaints, psychosocial stressors and diagnoses. Initial analysis of the results indicates that further research is necessary into the prevalence of anxiety disorders, the effects of regular exposure to high levels of violence and the effects of multiple substitute parents. The study highlights trends and indicates where strategies are necessary to direct resources and to initiate prevention. The high case load of school-related disorders (including learning disorders and attention deficit disorder) demonstrates the need for the educational authorities to review current educational practices. The absence of a clear referral process from primary to secondary to tertiary results in an overload on the clinics and must be urgently addressed. In addition, intersectoral liaison between health, welfare, education and justice departments must be developed in order for children to receive the best care possible.

Adolescent↗
PubMed1999

Treatment of acute hepatitis C virus infection.

Chronic hepatitis C is the leading cause of liver-related morbidity and mortality in the Western world. Treatment response in the chronic phase of the disease is still unsatisfactory. Acute hepatitis C takes a chronic course in more than 50% of cases. Interferon therapy treatment in the acute presentation phase is, according to some studies, more efficient than in the chronic phase of disease. The aim of this study was to analyse the response to interferon in acute hepatitis C. This review is based on three published meta-analyses performed using the methods of DerSimonian and Laird. Outcome was assessed by normalisation of serum aminotransferases and clearance of HCV-RNA. Data were presented by calculating the risk difference, which estimated efficacy by calculating the proportion of patients in treatment groups who responded better (0 to 1.0) or worse (0 to -1.0) than untreated control groups. Three mega units of interferon-a2b (IFN) three times a week for 6-24 weeks produced a significant response as measured by long-term normalisation of aminotransferases and clearance of HCV-RNA. Overall rate differences were +0.31 (p<0.01; 95% confidence interval +0.19-0.43) and +0.33 (p<0.001; 95% confidence interval +0.08-0.58). Six MU of IFN three times a week for 16-24 weeks produced better results with a risk difference of +0.53 (95% confidence interval +0.17-0.89) for normalisation of aminotransferases and +0.44 (95% confidence interval +0.06-0.82) for clearance of HCV-RNA. In an uncontrolled trial, 10 MU IFN daily for 4-6 weeks produced clearance of HCV-RNA and normalisation of transaminases in 90% of patients. Twelve weeks' treatment of symptomatic acute hepatitis C with interferon produced a response similar to that of long-term treatment for chronic hepatitis C. More studies are needed to define the role of a higher dose and the start of treatment.

Acute Disease↗
PubMed1999

Reversible severe myopathy of respiratory muscles due to adult-onset type III glycogenosis.

Subacute severe myopathy of the respiratory muscles developed in a 47-year-old woman after a 3-week period of strict fasting. Histological and biochemical work-up of muscle biopsy specimens permitted the diagnosis of debrancher deficiency. The course of the disease was characterized by subacute respiratory failure and prolonged mechanical ventilation. After initiation of a high-protein diet the patient was successfully weaned from the respirator and recovered well. To our knowledge this is the first reported case of adult-onset debrancher deficiency myopathy presenting with subacute respiratory failure and responding to high-protein diet.

Age of Onset↗
PubMed1999

ZOO-FISH analysis in a species of the order Chiroptera: Glossophaga soricina (Phyllostomidae).

Glossophaga soricina is a flower-visiting bat which lives in the neotropics. The diploid chromosome number is 2n = 32 with a fundamental number of autosomal arms, FN, of 60. G. soricina belongs to the Microchiroptera which have a lower diploid DNA content and a higher AT composition in their DNA compared with other mammals. By ZOO-FISH analysis with human chromosome-specific DNA probes, the human autosomes were found conserved in 41 segments. This is an arrangement similar to other mammals which have been analyzed. Several chromosomal associations already known from ZOO-FISH studies in other species were also present in G. soricina.

Animals↗
PubMed1999

Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis carinii infection in a liver transplant patient receiving tacrolimus.

We report on a case of bronchiolitis obliterans organizing pneumonia (BOOP) associated with Pneumocystis carinii pneumonia (PCP) after liver transplantation and tacrolimus based immunosuppression. Radiologically, bilateral diffuse interstitial shadowing and patchy alveolar infiltrates developed after switching the patient from cyclosporin A to tacrolimus for persistent rejection. Bronchoalveolar lavage (BAL) fluid showed inflammatory cells but no pathogenic organisms. Open lung biopsy revealed BOOP with granulomatous PCP. Thus, even in the case of negative BAL the possibility of an atypical P. carinii infection has to be considered for differential diagnosis of pneumonia in immunocompromised patients after organ transplantation. The combination of BOOP with PCP after liver transplantation and tacrolimus medication has not been reported previously.

Cryptogenic Organizing Pneumonia↗
PubMed1999

(CAG)nCAA and GGN repeats in the human androgen receptor gene are not associated with prostate cancer in a French-German population.

Alleles of the CAG and the GGC repeat in the first exon of the human androgen receptor (AR) gene have been shown to be associated with the risk of (advanced) prostate cancer. These studies had been carried out in the United States. We have analysed these polymorphisms in a French-German collection of 105 controls, 132 sporadic cases, and a sample of prostate cancer families comprising 85 affected and 46 not affected family members. The allele distributions were very similar in all four groups and chi square statistics on contingency tables did not detect any significant differences. The relative risk (odds ratio, OR) were calculated using logistic regression and did not reach significance despite sufficient numbers of patients and controls. Typical results were OR = 1.007; 95% Confidence Interval (CI) 0.97-1.1, P = 0.87 for CAG as continuous variable and OR = 1.2 (95% CI 0.7-2.0), P = 0.47 for CAG classes < 22 and > = 22 repeats. Similar results were obtained for subgroups defined by age or Gleason score. We conclude that these polymorphisms can not be used as predictive parameters for prostate cancer in the French or German population.

Aged↗
PubMed1999

Cutaneous lesions as the presenting sign of acute graft-versus-host disease following liver transplantation.

Acute graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation but is only rarely observed after solid organ transplantation. We describe a 68-year-old man who developed a maculopapular eruption 7 days following orthotopic liver transplantation for cirrhosis with malignant transformation due to haemochromatosis. At day 20, the patient complained of nausea, vomiting, diarrhoea and fever. Skin biopsy revealed a lymphocytic infiltrate at the dermoepidermal interface, vacuolization of basal cells and epidermal dyskeratosis. Immunohistochemistry showed HLA-DR and intercellular adhesion molecule-1 expression of lesional keratinocytes. HLA-typing of peripheral blood lymphocytes demonstrated circulating lymphocytes of donor origin. Endoscopy revealed extensive erosions of the oesophagus, stomach and duodenum that on histology disclosed multifocal loss of crypts, lymphocytic infiltrates and epithelial cell death. A diagnosis of acute GVHD was made, and high-dose immunosuppressive therapy with azathioprine and methylprednisolone was instituted. The skin and gastrointestinal symptoms subsided within 4 weeks, but the patient died from severe infectious complications 105 days after transplantation. We conclude that acute GVHD is a rare but potentially fatal complication of liver transplantation. Skin lesions are an early sign of acute GVHD and thus represent an important tool for early diagnosis.

Acute Disease↗
PubMed1999

Interferon-alpha (IFN-alpha) enhances cytotoxicity in healthy volunteers and chronic hepatitis C infection mainly by the perforin pathway.

Cell-mediated cytotoxicity is exerted via perforin and Fas ligand (FasL). We have recently shown that IFN-alpha up-regulates FasL expression in T cells isolated from healthy volunteers and augments activation-induced T cell death. Since the Fas/FasL system is implicated in the pathogenesis of hepatic failure and both molecules have been shown to be up-regulated in hepatitis C virus (HCV) infection, we studied whether cytotoxicity via the FasL system is enhanced by IFN-alpha and therefore could contribute to hepatic injury. We investigated FasL and perforin expression in peripheral blood mononuclear cells (PBMC) derived from HCV+ donors by Northern analysis and soluble FasL synthesis by ELISA. Natural killer (NK) cell and cytotoxic T lymphocyte (CTL) cytotoxicity was studied by 51Cr-release assays. IFN-alpha up-regulates FasL mRNA and protein synthesis in mitogen-activated PBMC of HCV+ individuals, as previously found in healthy subjects. Stimulation with IFN-alpha increases perforin mRNA levels in PBMC. In NK cytotoxicity assays, the enhancement of cytotoxicity by IFN-alpha is mainly due to the perforin pathway, while the FasL pathway plays only a minor role. In CTL cytotoxicity experiments neither the FasL nor the perforin pathway is further enhanced by IFN-alpha. Our data suggest that up-regulation of perforin by IFN-alpha results in elevated cytotoxicity, suggesting that IFN-alpha might support elimination of virally infected cells via this pathway. In contrast, the major effect of IFN-alpha on the Fas/FasL system might be the enhanced elimination of activated T cells as a means of finally limiting a T cell response.

Anti-Bacterial Agents↗
PubMed1999

Effect of bupivacaine on ATP-dependent potassium channels in rat cardiomyocytes.

Bupivacaine induces fatal arrhythmia when accidentally injected i.v. or overdosed, whereas lidocaine is used as an anti-arrhythmic agent. We have suggested recently that the anti-arrhythmic effect of lidocaine may be explained by suppression of ATP-sensitive potassium (KATP) channels. Therefore, it could be argued that different sensitivities of KATP channels to both drugs could be a reason for their different arrhythmic and anti-arrhythmic properties. In this study, we have investigated the direct action of bupivacaine on KATP channels in cardiomyocytes. The effects of bupivacaine on the cardiac KATP channel were investigated using the patch-clamp technique on enzymatically dissociated cardiomyocytes of adult rats. Bupivacaine was applied to the outer side of excised membrane patches using a multiple-barrel perfusion system. Concentration-response curves indicated that bupivacaine blocked the mean current of the KATP channels at a half-maximum inhibiting concentration (IC50) of 29 mumol litre-1, similar to that reported for lidocaine (43 mumol litre-1). Binding of bupivacaine influenced the gating of this channel, but did not reduce the conductance of the open channel. Bupivacaine and lidocaine were equipotent in blocking KATP channels. However, because of its excessive block of the sodium channel in the inactivated state, block of KATP channels by bupivacaine will only enhance its cardiotoxicity.

Adenosine Triphosphate↗