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Biomedical subjects

W Meister

Publications and source records attributed to W Meister.

At least 19 recordsLinked to original sources
PubMed2006

Survival, and time to an advanced disease state or progression, of untreated patients with moderately severe multiple sclerosis in a multicenter observational database: relevance for design of a clinical trial for high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation.

Despite prolonged survival, patients with multiple sclerosis (MS) experience considerable morbidity, which adversely impacts quality of life. To assess the risk-benefit of a clinical trial of high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation for MS, we sought to determine the natural history of the disease in a comparison group of untreated patients. We identified 285 individuals with 2132 combined observation years (median: 5.6 years; 5th to 95th percentile: 1-21 years), with Expanded Disability Status Scale (EDSS) scores of 3.0-5.5 at baseline observation. Disease-related mortality was zero at five years, 5.4% at 10 years, and 22% at 15 years (40 patients contributing to the data point; 95% confidence interval: 4-32%). Risk for progression to advanced disability, defined as an EDSS score of 8, was very low for the subgroup with a baseline EDSS score of 3-3.5; however, for those with a baseline EDSS score of 4-5.5, 3% had advanced disability after two years, 5% after three years, 6% after four years, 12% after five years, and 40% after 10 years. The estimated probability of disease progression, defined as an increase in EDSS score by > or = 1.0 sustained for at least 180 days, was 5% after one year, 14% after two years, 22% after three years, 38% after five years, 57% after 10 years, and >80% after 20 years of observation. The relevance of these features to the design of the clinical trial is discussed.

Clinical Trials as Topic↗
PubMed2002

[Prevalence, detection and prescribing behavior in depressive syndromes. A German federal family physician study].

This study examines the prevalence of depressive syndromes among unselected primary care patients as well as doctors' recognition and treatment rates. This nationwide study included a total of 20,421 patients attending their primary care doctors (n = 633) on the study's target day. Patients received a self-report questionnaire including the depression screening questionnaire (DSQ) to provide diagnoses of depressive disorders according to the criteria of DSM-IV and ICD-10. These data were compared to the doctor's evaluation form for each patient to assess the physician's diagnostic decision, assessment of clinical severity, and treatment choices. The findings confirm the high prevalence of depressive syndromes in primary care settings (11.3%) and underline the particular challenge posed by a high proportion of patients near the diagnosis threshold. Although recognition rates among more severe major depressive patients (59%) as well as treatments prescribed appear to be more favourable than in previous studies, the situation in less severe cases and the high proportion of doctors' definite depression diagnoses in patients who do not fulfill the diagnostic criteria still raise significant concerns.

Adolescent↗
PubMed2001

Prevalence and recognition of depressive syndromes in German primary care settings: poorly recognized and treated?

The study examines the prevalence of depressive syndromes among unselected primary care attenders, as well as doctors' recognition and treatment rates, in order to examine patient and doctor-related factors associated with poor recognition. This nationwide study included a total of 20421 patients (aged 15-99 years) attending their primary care doctors (n = 633) on the study's target day in April 1999. Patients received a self-report questionnaire, including the Depression Screening Questionnaire (DSQ), to provide diagnoses of depressive disorders according to the criteria of DSM-IV and ICD-10. Doctors completed: (1) a pre-study questionnaire assessing data on doctors' psychosocial, professional and training background, as well as current practices in patients with depression and (2) an evaluation form for each patient seen to assess his diagnostic decision, clinical severity and treatment choices. Taking the DSQ as a yardstick, 4.2% of all primary care attenders fulfilled criteria for a major depressive episode according to DSM-IV; considerably higher rates of 11.3% were obtained using the ICD-10 criteria for mild depressive episodes. Rates of depression were higher in females, increased by age, and were also elevated in those retired, unemployed as well as non-working housemen/wives. Taking the doctors' decision of definite or probable depression, 75% of all DSM and 59% of all ICD-10 diagnoses were recognized by the treating physician. However, doctors also assigned diagnoses of definite depression in an additional 11.7% of patients not meeting either ICD-10 nor DSM-IV criteria. Among correctly identified depression cases doctors decided to prescribe drug treatments in 72.7% (DSM) and 60.8% (ICD). Some 16.2% of DSM and 10.1% of ICD-cases were referred to mental health specialists; non-drug interventions were prescribed for 19.8% (DSM) and 24.9% (ICD), respectively. Multiple logistic regression analyses revealed that recognition is associated with prior treatment episodes, increasing number of depression symptoms, patients higher age, practice experience of treating physician greater 5 years and psychomotor retardation. These findings confirm the high prevalence of depressive syndromes in primary care settings and underline the particular challenge posed by a high proportion of with near-threshold symptomology patients. Although recognition rates among more severe major depressive patients as well as treatments prescribed appear to be more favourable than in previous studies, the situation in less severe cases, and the high proportion of doctors' definite depression diagnoses in patients with depression symptoms that are clearly below even the subthreshold level, raises significant concerns.

Adolescent↗
PubMed2000

[Amoxicillin/clavulanic acid in therapy of bacterial infections of the diabetic foot. Results of an observational study].

The results of an observational study of amoxicillin/clavulanic acid (Augmentan) in 191 patients are presented. The average duration of treatment was 15 days (median). Healing or improvement was observed in 76% of the cases. In view of the fact that the condition often has a multifactorial genesis and neural and vascular changes impair healing, this result must be considered a clinical success. Variables with an influence on the efficacy of the treatment were the incidence of manifestation and pathogenesis of the ulcer, renal function, blood pressure and smoking. Amoxicillin/clavulanic acid was well tolerated, with adverse events being observed in only 9 out of 193 patients (4.7%). Treatment was abandoned because of adverse events in 3 out of 193 patients (1.6%). Overall, treatment of the infected diabetic foot with amoxicillin/clavulanic acid was well tolerated and effective.

Adult↗
PubMed1999

Characterization of antigens from the human exocrine pancreatic tissue (Pag) relevant as target antigens for autoantibodies in Crohn's disease.

BACKGROUND: The present study was performed to analyse the immunological properties of the autoantigens recognized by autoantibodies against exocrine pancreas (PAb), which have been described in Crohn's disease. METHODS: Autoantibodies were detected by indirect immunofluorescence. Inhibition studies were performed by preincubating tissue sections with various glycoproteins and the different fractions obtained in fractioned salt precipitation of pancreas homogenate with ammonium sulphate. Immunoblotting of human pancreas homogenate was conducted using PAb-positive sera. RESULTS: In size exclusion chromatography, the molecular weight of the pancreas autoantigen (PAg) was determined as > 800 kD. In the fractionated salt precipitation, the autoantigen could be detected in fractions I (0-25% ammonium sulphate) and III (50-90% ammonium sulphate). In immunoblotting, a number of protein bands were observed (at 16, 18, 19, 24, 27, 29, 31 and 34 kD), and the binding pattern showed little variation between individual patients. CONCLUSIONS: The protein that is recognized by PAb appears to be a large protein complex consisting of several subunits which exhibit reactivity to PAb.

Autoantibodies↗
PubMed1999

Paroxetine and amitriptyline augmentation of lithium in the treatment of major depression: a double-blind study.

To study the efficacy and safety of antidepressant augmentation of ongoing lithium therapy, lithium-maintained patients suffering from an breakthrough episode of major depression were randomly assigned under double-blind conditions to receive paroxetine 20 mg/day (N = 19) or amitriptyline 75 mg/day (N = 23). The initial dosages could be increased after 2 weeks to 40 mg/day and 150 mg/day, respectively, and the patients were treated for a total of 6 weeks. Efficacy was assessed weekly with the 21-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression Scale (CGI), and safety was assessed with the Dosage Record and Treatment Emergent Symptom Scale. After 4 weeks, a significantly greater proportion of patients in the paroxetine group had achieved a 50% reduction in baseline HAM-D scores, and the mean improvement in CGI severity of illness was significantly greater in the paroxetine group at weeks 3 and 5. The type and number of emergent events occurring during study treatment corresponded to the known side effect profiles of paroxetine and amitriptyline. Serum lithium levels were not affected by either antidepressant. The authors proposed that the more rapid improvement demonstrated by the group receiving the combination of lithium and paroxetine may be due to the synergistic serotonergic effects of these two medications.

Adult↗
PubMed1998

Demography, symptomatology, and course of disease in ambulatory zoster patients. A physician-based survey in Germany.

This survey summarises the observations of physicians who prospectively recorded clinically relevant data on their patients with an episode of herpes zoster. These included demography of patients, signs and symptoms during the prodromal phase, relevant history, description of disease at the first visit, therapeutic measures and description of disease, and occurrence of postherpetic neuralgia (pain 4-5 weeks after crusting) at the second visit. A total of 2,063 patients were reported to the data management centre. The age distribution resembles that reported in the literature including the notable increase in zoster frequency with advancing age. Almost 20% of the patients, however, were 30 years old or less, and this contrasts markedly with the published literature. Age modifies the frequency of the dermatome afflicted: more cranial and less thoracic manifestations were observed with increasing age. Almost all patients reported symptoms which may be attributed to a prodromal phase, especially pain in the affected dermatome (82%). The incidence of postherpetic neuralgia was 28%. A complicated disease course such as visceral, ocular, or otological involvement, or progression to additional dermatomes was seen in almost 10% of the patients.

Adolescent↗
PubMed1997

The influence of strongly acidic groups on the protonation of peptides in electrospray MS.

In order to obtain experimental data on the question of compensation of positive charges by anionic groups in multiply charged ions of polyfunctional molecules in electrospray MS, several pairs of peptides with the same basic structure but differentiated by one or two strongly acidic groups (phosphate or sulfonate) were investigated. It was found that depending on the density of basic centers and the strength of acidic groups present, the observed changes upon introduction of acidic groups ranged from complete elimination of the most highly charged state to absence of any difference.

Amino Acid Sequence↗
PubMed1997

The treatment of depression with paroxetine in psychiatric practice in Germany: the possibilities and current limitations of drug monitoring.

A drug monitoring of the antidepressant paroxetine was carried out in Germany from August 1992 to November 1993. The principal aim of this study was to collect demographic, diagnostic, efficacy, and medical-safety data regarding patients who were treated for up to 12 weeks with this SSRI. A secondary goal was the investigation of differences between patients who left treatment after 6 weeks or earlier and those who continued treatment. Evaluable data were obtained from 507 psychiatrists for 2817 patients, 1301 of whom extended treatment beyond 6 weeks. 64% of the patients had been pretreated for the current episode of depression. 50% were considered by their doctors to have either chronic or recurrent illness and 92% to possess moderate to severe symptomatology. Concomitant psychotropic medication was reported in 43% of cases, the most frequent medications being benzodiazepines, neuroleptics, and/or tricyclic antidepressants. Clear or complete improvement was noted for 63% of assessable patients by the end of week 6 and for 79% of the patients who extended treatment to 12 weeks. There were significantly more patients with DSM major depression and severe symptoms in the treatment-extender than in the 6-week treatment group. Paroxetine was tolerated well by most patients: of the 1009 adverse events reported, only 17 were considered "serious". There were no suicides or cases of overdose attributable to paroxetine. The discussion of these results is the basis for a critical appraisal of postmarketing-surveillance methodology. It is concluded that, despite its present structural weaknesses as compared to controlled investigations, drug monitoring of a new medication in the immediate postmarketing period can give insights into the treatment of large numbers of patients under private-practice conditions. However, drug monitoring as it is conducted in Germany can have different and perhaps conflicting functions which may limit its effectiveness. The authors recommend that all interested parties (physicians, the pharmaceutical industry, regulatory bodies) engage in a continuous dialog aimed at clearly formulating the goals and improving the methodology of drug monitoring.

Adult↗
PubMed1997

Dose escalation vs. continued doses of paroxetine and maprotiline: a prospective study in depressed out-patients with inadequate treatment response.

In view of the fact that controlled prospective studies on the benefits of dose escalation of the selective serotonin re-uptake inhibitor (SSRI) paroxetine are lacking, we conducted a double-blind, randomized, parallel-group multicentre study designed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria (RDC) with inadequate treatment response. The study sample consisted of 544 out-patients with different degrees of severity of depression. Patients received either 20 mg paroxetine (n = 271) or 100 mg maprotiline (n = 273) for the first 3 weeks in a double-blind manner. Response after 3 weeks was defined using explicit operationalized criteria. Patients with inadequate treatment response (paroxetine group, n = 86; maprotiline group, n = 88) were again randomized to either continuation of the previous dosage (paroxetine, n = 36; maprotiline, n = 48) or increased doses, i.e. 40 mg paroxetine (n = 50) or 150 mg maprotiline (n = 40), respectively. Intention-to-treat and completer analyses were performed. Defining response as a reduction in Hamilton Depression Rating Scale (17-item version) (HAMD-17) score of at least 50% from baseline, no significant benefits of dose escalation were found for either paroxetine or maprotiline. Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation. After dose escalation, new adverse events that had not been present during treatment with lower doses rarely occurred. Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients.

Adult↗
PubMed1996

TCR- and IL-1-mediated co-stimulation reveals an IL-4-independent way of Th2 cell proliferation.

Previously, it has been shown that Th1 cells, when triggered solely via their TCR, are blocked from proliferation in response to IL-2. Herein, we describe a similar characteristic for Th2 cells in that immobilized mAb directed to the TCR blocked proliferation of Th2 cells in response to IL-4. This "proliferative block' was observed in all four Th2 cell clones tested, but not in a subline of one of the clones which has been cultured in vitro for several years. Addition of IL-1 neutralized the proliferative block in all four Th2 cell clones. Surprisingly, blocking experiments with sIL-4R and anti-IL-4 mAb revealed that in three out of four Th2 cell clones this effect of IL-1 was IL-4-independent and could also not be blocked by cyclosporin A (CsA). In contrast, the proliferation of one Th2 cell clone in response to the TCR- and IL-1-mediated signals was indeed inhibited by sIL-4R, anti-IL-4 mAb and CsA. Thus, our data illustrate that in addition to the well-known IL-4-dependent proliferation, there also exists an IL-4-independent, IL-1-mediated way of Th2 cell proliferation.

Animals↗
PubMed1996

Excretion and metabolism of remikiren, a potent orally active inhibitor of primate renin.

1. Following intravenous administration of 14C-remikiren to the male rat, 78% of the administered radioactivity was recovered in faeces, indicating high biliary elimination. Of the 25 +/- 0.1% of the dose recovered in urine, the majority (16.5% of dose) was intact drug. 2. After oral administration to the male rat the urinary recovery was markedly reduced (8.5 +/- 2.0% of dose), and virtually all of the material was excreted as an inactive hydrolysis product. Intact drug was non-detectable, suggesting extensive first-pass metabolism. 3. Perfusion of isolated rat liver confirmed high biliary elimination, coupled with extensive metabolism. Although intact remikiren was the major component in bile (20% of the 'dose'), the majority of the radioactivity was recovered as a series of mono- and di-hydroxylated metabolites. 4. When screened against human renin, only one of the metabolites in bile and urine (mono-hydroxylated in the t-butyl side chain, and synthesized as Ro 44-0444) showed comparable activity to remikiren. The remaining ten metabolites tested were at least one order of magnitude less active than the parent drug. 5. In comparative in vitro studies Ro 44-0444 was formed by rat, but not human or cynomolgus monkey, liver microsomes. The primate microsomes also produced more of the remaining mono- and di-hydroxy products, suggesting that metabolites make little contribution to the oral activity of remikiren which is observed in these species in vivo.

Administration, Oral↗
PubMed1991

Heparin treatment in sinus venous thrombosis.

Treatment of sinus venous thrombosis (SVT) is controversial. Although heparin has been used for this condition, many investigators have opposed its use because of the frequent occurrence of intracranial haemorrhage (ICH) and SVT. Therefore we have evaluated anticoagulation with adjusted-dose intravenous heparin for treatment of aseptic SVT in a randomised, blinded (patient and observer), placebo-controlled study in 20 patients (10 heparin, 10 placebo). The clinical course of the two groups, as judged by a newly designed SVT-severity scale, started to differ in favour of the heparin group after 3 days of treatment (p less than 0.05, Mann-Whitney U-test) and the difference remained significant (p less than 0.01) after 8 days of treatment. After 3 months, 8 of the heparin-treated patients had a complete clinical recovery and 2 had slight residual neurological deficits. In the placebo group, only 1 patient had a complete recovery, 6 patients had neurological deficits, and 3 patients died (p less than 0.01, modified Fisher's exact test). An additional retrospective study on the relation between heparin treatment and ICH in SVT patients was based on 102 patients, 43 of whom had an ICH. 27 of these patients were treated with dose-adjusted, intravenous heparin after the ICH. Of these 27 patients, 4 died (mortality 15%), and 14 patients completely recovered. Of the 13 patients that did not receive heparin after ICH, 9 died (mortality 69%) and only 3 patients completely recovered. We conclude that anticoagulation with dose-adjusted intravenous heparin is an effective treatment in patients with SVT and that ICH is not a contraindication to heparin treatment in these patients.

Adult↗
PubMed1991

The lipase inhibitor tetrahydrolipstatin binds covalently to the putative active site serine of pancreatic lipase.

Tetrahydrolipstatin (THL) is a selective inhibitor of fat absorption. In animal models, it has anti-obesity and anti-hypercholesterolemic activity and is presently in clinical trials for these indications. THL binds covalently to pancreatic lipase. Complete inhibition of lipolytic activity is obtained concomitant with the incorporation of 1 mol of THL/mol of enzyme. Pancreatic lipase is the best studied lipase, but published results concerning its catalytic mechanism are still controversial. In order to learn more about the inhibitory mechanism of THL, a selective lipase inhibitor interacting at or near the catalytic site, and therefore, to obtain more information on the catalytic mechanism of lipase, we have determined the amino acid residue to which THL is bound. After proteolytic degradation of porcine pancreatic lipase inhibited with radioactively labeled THL, the labeled peptides were isolated and analyzed by quantitative amino acid analysis, N-terminal sequencing, and by mass spectrometry with fast atom bombardment ionization. The data clearly show that THL is bound as an ester to the serine 152 of the lipase.

Amino Acid Sequence↗
PubMed1990

Biotransformation of moclobemide in humans.

The structure of the urinary metabolites formed after moclobemide administration in human was elucidated, and the pattern compared with that in the plasma. The metabolic pathways of moclobemide were also compared with those of structurally related substances. After oral moclobemide administration, on average 95% of the dose was recovered in the urine within 4 days, with a mean of 92% being excreted during the first 12 h. The drug is extensively metabolized: less than 1% of the dose was excreted unchanged. A total of 19 metabolites, accounting together for about 64% of the dose, was isolated and all metabolites accounting for more than 1% of the dose were identified. Consistent with other morpholine-containing compounds, metabolic pathways of moclobemide include mainly oxidative attack on the morpholine moiety, leading to a multitude of oxidation products. Four primary metabolic reactions were identified: morpholine N-oxidation, aromatic hydroxylation, morpholine C-oxidation and deamination. The major metabolites in urine are 4 carboxylic acids (M7A and M7B, M8, M9) that account for 49% of the dose. Only 2 metabolites (M3, M10) were found to be hydroxylated on the aromatic nucleus. They were excreted completely as conjugates of glucuronic and/or sulfuric acid. Conjugation in general, however, seems to be of minor importance in the overall biotransformation of the drug. The metabolite pattern in plasma was found to be qualitatively but not quantitatively similar to that observed in urine. Almost all of the main urinary metabolites were found in plasma as well. The unchanged parent compound and 2 primary oxidation products of the morpholine ring (M1, M15), which were present in urine only in trace amounts, could easily be detected in plasma.

Administration, Oral↗