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Biomedical subjects

Peter Bauer

Publications and source records attributed to Peter Bauer.

At least 55 records · Page 3Linked to original sources
PubMed2004

Lack of mutations in the epsilon-sarcoglycan gene in patients with different subtypes of primary dystonias.

Primary dystonias represent a clinically and genetically heterogeneous group of movement disorders. Mutations in the epsilon-sarcoglycan (SGCE) gene have been found recently to cause myoclonus-dystonia (MD). Considerable clinical variation of SGCE mutation carriers leads to the hypothesis that mutations in the SGCE gene might also be relevant for other subtypes of dystonias. To determine the contribution of mutations in the SGCE gene in patients with different subtypes of dystonias, we analyzed the coding sequence of the SGCE gene in a group of 296 patients with a clinical phenotype of primary dystonia and in 2 patients with a clinical phenotype of myoclonus-dystonia. Patients with mutations in the DYT1 gene were excluded. We could not detect a mutation in the SGCE gene in any of the 298 patients. Our results suggest that mutations in the SGCE gene cannot be held responsible for other subtypes of primary dystonia.

Adult↗
PubMed2004

Mutation at the SCA17 locus is not a common cause of primary dystonia.

Spinocerebellar ataxia type 17 (SCA17) is a dominant progressive neurodegenerative disorder, caused by a triplet repeat expansion within the TATA-binding protein. As well as ataxia and dementia, Parkinsonism and dystonia are common in SCA17. In some pedigrees focal dystonia in the absence of ataxia has been described as a main clinical feature. To evaluate the relevance of SCA17 mutations for primary dystonia, we examined the TBP repeat expansion in a series of 288 patients with different subtypes of primary torsion dystonia. We did not find any repeat sizes in the pathogenic range. We conclude that the SCA17 repeat expansion is not a common cause of familial and sporadic dystonia.

Adult↗
PubMed2004

Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial.

AIMS: In patients with persistent atrial fibrillation (AF), the efficacy and safety of two anti-arrhythmic drugs in preventing the recurrence of AF after successful direct current (DC) cardioversion was prospectively assessed in a multi-centre double-blind, placebo-controlled, randomised trial using daily trans-telephonic monitoring. METHODS AND RESULTS: 1182 patients with persistent AF were prospectively enrolled, 848 patients were successfully cardioverted and then randomised to either sotalol (383 patients), quinidine plus verapamil (377 patients) or placebo (88 patients). The primary outcome parameter was AF recurrence or death. All patients received an event recorder (Tele-ECG) and had to record and transmit via telephone at least one ECG per day during follow-up. The mean follow-up period was 266 days. A total of 191,103 Tele-ECGs were recorded and transmitted. The primary outcome parameter (AF recurrence of any kind or death) was observed in 572 patients (67%) in whom at least one episode of AF recurrence was documented during follow-up, in 348 patients (41%) AF recurrence was persistent. The recurrence rates after one year for any AF were 83% for placebo, 67% for sotalol and 65% for quinidine plus verapamil, the latter being statistically superior to placebo but not different from sotalol. The recurrence rates for the secondary outcome parameter persistent AF were 77%, 49% and 38%, respectively. Quinidine plus verapamil was significantly superior to placebo and to sotalol. About 95% of all AF recurrences were initially detected in the daily Tele-ECG, about 70% of all AF recurrences occurred completely asymptomatic. Adverse events on sotalol and quinidine plus verapamil were comparable with the exception that all torsade de pointes tachycardias occurred on sotalol. CONCLUSION: Anti-arrhythmic treatment after DC cardioversion of persistent AF significantly decreases the recurrence rates of persistent AF compared to placebo with superiority of quinidine plus verapamil compared to sotalol. Symptoms were not reliable as clinical surrogates to detect episodes of AF.

Adolescent↗
PubMed2004

Suppression of paroxysmal atrial tachyarrhythmias--results of the SOPAT trial.

AIM: The indication to treat paroxysmal atrial fibrillation (PAF) is controversial. The Suppression of Paroxysmal Atrial Tachyarrhythmias (SOPAT) trial was designed to answer the following questions: (1) What is the average rate of spontaneous events of symptomatic PAF with and without anti-arrhythmic medication? (2) what is the prevalence of severe side-effects? and (3) is the fixed combination of Quinidine + Verapamil inferior to the efficacy of sotalol or not? METHODS AND RESULTS: Within 60 months 172 centres in Germany, Poland, and The Slovak Republic prospectively enrolled 1033 patients (mean age 60 years, 62% male) with documented frequent episodes of symptomatic PAF. Patients were randomised to either Quinidine + Verapamil 480/240 mg/d (high dose; 263 patients), Quinidine + Verapamil 320/160 mg/d (low dose; 255 patients), Sotalol 320 mg/d (264 patients) or placebo (251 patients), of which 1012 patients entered the intention-to-treat analysis. The primary endpoint was the time to first recurrence of symptomatic PAF or premature discontinuation. Secondary outcome parameters were the total number of symptomatic episodes and tolerability of the tested drugs. Patients were followed for a period of up to 12 months by daily and symptom-triggered trans-telephonic ECG-monitoring (Tele-ECG). The mean time under treatment was 233 +/- 152 days. Regarding the primary endpoint, all active treatments were superior to placebo and not different from each other. A total of 756 patients reached the primary endpoint within 105.7 +/- 8.7 d (mean +/- SEM) in the placebo group, vs. Quinidine + Verapamil (high dose) (150.4 +/- 10 d, p = 0.0061), vs. Quinidine + Verapamil (low dose) (148.9 +/- 10.6 d, p = 0.0006), vs. Sotalol (145.6 +/- 93 d, p = 0.0007). All three treatments were also effective in the reduction of AF burden (days with symptomatic AF [%] mean +/- SD, p vs. placebo): Quinidine + Verapamil (high dose) (3.4 +/- 12, p = 0.0001), Quinidine + Verapamil (low dose) (4.5 +/- 12.3, p = 0.008) and Sotalol (2.9 +/- 6.5, p = 0.026) compared to placebo (6.1 +/- 13.5). A total of four deaths, 13 syncopes, and one ventricular tachycardia (VT) occurred during the active study period, of which one death and one VT were related to Quinidine/Verapamil. CONCLUSION: Taken together, anti-arrhythmic therapy with the fixed combination of Quinidine + Verapamil is as effective as Sotalol in the reduction of the recurrence rate of symptomatic PAF with a low but definite risk of severe side-effects.

Adolescent↗
PubMed2004

Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis.

Autosomal dominant cerebellar ataxias are hereditary neurodegenerative disorders that are known as spinocerebellar ataxias (SCA) in genetic nomenclature. In the pregenomic era, ataxias were some of the most poorly understood neurological disorders; the unravelling of their molecular basis enabled precise diagnosis in vivo and explained many clinical phenomena such as anticipation and variable phenotypes even within one family. However, the discovery of many ataxia genes and loci in the past decade threatens to cause more confusion than optimism among clinicians. Therefore, the provision of guidance for genetic testing according to clinical findings and frequencies of SCA subtypes in different ethnic groups is a major challenge. The identification of ataxia genes raises hope that essential pathogenetic mechanisms causing SCA will become more and more apparent. Elucidation of the pathogenesis of SCA hopefully will enable the development of rational therapies for this group of disorders, which currently can only be treated symptomatically.

Cell Death↗
PubMed2004

Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.

Acute renal failure increases risk of death after cardiac surgery. However, it is not known whether more subtle changes in renal function might have an impact on outcome. Thus, the association between small serum creatinine changes after surgery and mortality, independent of other established perioperative risk indicators, was analyzed. In a prospective cohort study in 4118 patients who underwent cardiac and thoracic aortic surgery, the effect of changes in serum creatinine within 48 h postoperatively on 30-d mortality was analyzed. Cox regression was used to correct for various established demographic preoperative risk indicators, intraoperative parameters, and postoperative complications. In the 2441 patients in whom serum creatinine decreased, early mortality was 2.6% in contrast to 8.9% in patients with increased postoperative serum creatinine values. Patients with large decreases (DeltaCrea <-0.3 mg/dl) showed a progressively increasing 30-d mortality (16 of 199 [8%]). Mortality was lowest (47 of 2195 [2.1%]) in patients in whom serum creatinine decreased to a maximum of -0.3 mg/dl; mortality increased to 6% in patients in whom serum creatinine remained unchanged or increased up to 0.5 mg/dl. Mortality (65 of 200 [32.5%]) was highest in patients in whom creatinine increased > or =0.5 mg/dl. For all groups, increases in mortality remained significant in multivariate analyses, including postoperative renal replacement therapy. After cardiac and thoracic aortic surgery, 30-d mortality was lowest in patients with a slight postoperative decrease in serum creatinine. Any even minimal increase or profound decrease of serum creatinine was associated with a substantial decrease in survival.

Adolescent↗
PubMed2004

Optimal conditional error functions for the control of conditional power.

Ethical considerations and the competitive environment of clinical trials usually require that any given trial have sufficient power to detect a treatment advance. If at an interim analysis the available data are used to decide whether the trial is promising enough to be continued, investigators and sponsors often wish to have a high conditional power, which is the probability to reject the null hypothesis given the interim data and the alternative of interest. Under this requirement a design with interim sample size recalculation, which keeps the overall and conditional power at a prespecified value and preserves the overall type I error rate, is a reasonable alternative to a classical group sequential design, in which the conditional power is often too small. In this article two-stage designs with control of overall and conditional power are constructed that minimize the expected sample size, either for a simple point alternative or for a random mixture of alternatives given by a prior density for the efficacy parameter. The presented optimality result applies to trials with and without an interim hypothesis test; in addition, one can account for constraints such as a minimal sample size for the second stage. The optimal designs will be illustrated with an example, and will be compared to the frequently considered method of using the conditional type I error level of a group sequential design.

Biometry↗
PubMed2004

Subjective memory complaints and objective memory impairment in the Vienna-Transdanube aging community.

OBJECTIVES: To help answer the question of whether subjective memory complaints are a useful feature in classification systems addressing early stages of Alzheimer's disease. DESIGN: A cross-sectional investigation in the context of a community-based cohort study. SETTING: Vienna, Transdanube-a geographically defined, urban, working-class area. PARTICIPANTS: Three hundred two nondemented 75-year-olds were examined with regard to subjective memory complaints and objective memory performance. The patients were divided into two groups with respect to subjective memory complaints and into two groups with respect to memory performance on the Fuld Object Memory Evaluation. MEASUREMENTS: The percentage of individuals with memory complaints who also had objective memory impairment and the percentage of individuals with objective memory impairment who also complained about their memory were measured. RESULTS: One-tenth (10.6%) (95% confidence interval (CI)=7.7-14.7) of community based sample of 75-year-old subjects complained about their memory. There was no difference between complainers and noncomplainers with regard to actual memory performance. Only 6.3% (95% CI=0.16-30.2) of memory-impaired subjects complained about their proven memory impairment. CONCLUSION: About 94% (95% CI=69.8-99.8) of memory-impaired individuals do not complain about memory problems. Subjective memory complaints may not be a useful feature in current diagnostic criteria of mild cognitive impairment.

Aged↗
PubMed2004

Suicide in custody: case-control study.

BACKGROUND: Few risk factors and indicators of vulnerability for suicide in custody are known so far. AIMS: A case-control study was conducted to investigate the relevance of criminal history, psychiatric morbidity and social integration to suicide in prison. METHOD: For every suicide that occurred in an Austrian correctional institution between 1975 and 1999, two controls matched for correctional institution, gender, nationality, age, custodial status and time of admission were selected. Psychiatric characteristics, previous suicidal behaviour, criminal history and indicators of social integration were compared. RESULTS: Of 250 recorded suicides, 220 personal files were available and matched to 440 controls. The most important predictors for suicide in custody were a history of suicidality (status following attempted suicide and suicide threat), psychiatric diagnosis, psychotropic medication, a highly violent index offence and single- cell accommodation. CONCLUSIONS: A significant finding is the importance of suicidal behaviour as an indicator of risk of suicide in correctional institutions, which until now has been a matter of debate. This study demonstrates the need for staff to take suicidal behaviour as seriously in custodial settings as in any other circumstances.

Adolescent↗
PubMed2003

Reliability of a standardized reading chart system: variance component analysis, test-retest and inter-chart reliability.

BACKGROUND: The purpose of this study was to analyze statistically the test-retest and inter-chart reliability of three standardized Radner Reading Charts with respect to reading acuity, maximum reading speed, critical print size and LogRAD/LogMAR ratio and to quantitatively identify the sources of variability. METHODS: At two testing sessions (3 to 4 weeks apart), 36 volunteers read monocularly all three Radner Reading Charts in randomized order (orthogonal Latin square design). The subjects were grouped according to their distance LogMAR visual acuity (group 1, 0.1 or better; group 2, 0.12-0.4; group 3, 0.42-0.8). Based on these 216 reading tests, crude correlations were calculated between the two testing sessions and between the three charts, and "variance component analyses" were performed for all variables. RESULTS: For all visual acuity groups and variables, the test-retest and the inter-chart reliability was high. The variance component analyses showed that the differences between individuals predominantly influenced the variance, whereas the effect of the test replication was low. The three charts caused minimal variability, indicating equality for clinical examinations. CONCLUSION: The standardized Radner Reading Charts provide clinically reliable and reproducible results for individuals with normal eyesight and for patients with visual impairment. These findings indicate that reading test systems, which consider the current international standards for visual acuity measurements (EN ISO 8596, NAS-NRC) and the psychophysical requirements for controlling optical item interactions, can provide reliable measures for clinical and scientific analyses of reading performance.

Aged↗
PubMed2003

Screening for mutations of the ferritin light and heavy genes in Parkinson's disease patients with hyperechogenicity of the substantia nigra.

Recently, an insertional mutation in the ferritin-L gene was reported in some patients with familial basal ganglia degeneration, which, however, could not be detected in another Parkinson's disease (PD) population. We investigated 186 PD patients, in whom an increased amount of iron of the substantia nigra (SN) was priorly identified by transcranial ultrasound, for mutations of the whole coding region of ferritin-L and ferritin-H by denaturing high-pressure liquid chromatography and subsequent sequencing. In the ferritin-L gene two silent mutations were detected. In the ferritin-H gene the sequence variation 161A-->G was found in one patient but none of the 186 controls. Although functional analysis will show, whether this sequence variation might be causative for single cases of PD, the results indicate that mutations in the ferritin genes are not a common cause for PD with increased levels of iron of the SN.

Aged↗
PubMed2003

A replicate study design for testing bioequivalence: a case study on two desmopressin nasal spray preparations.

OBJECTIVE: The present study was carried out to test bioequivalence between two different desmopressin nasal spray preparations. Due to the high variability of plasma pharmacokinetics of intranasally administered peptides like desmopressin, appropriate study designs are required to assess bioequivalence. Therefore, a single-dose, replicate study design was used to evaluate bioequivalence of two desmopressin nasal sprays. SUBJECTS AND METHODS: Thirty-two healthy male volunteers were enrolled in the study and were randomly assigned to receive the test- and reference drug on two occasions in a 4-period 2-sequence crossover study design. Subjects received a single dose of 20 microg (10 microg per nostril) of desmopressin-acetate per study day separated by wash-out periods of at least 1 week. Desmopressin blood concentrations were measured serially over a 14-h period using a validated radioimmunoassay method. Statistical analysis was initially performed using a complicated mixed-analysis model testing for individual bioequivalence according to recommendations by the Food and Drug Administration. This approach, however, failed to converge with all defined main PK parameters and, thus, a traditional mixed analysis of variance analysis based on population averages was definitely used for testing bioequivalence between study drugs. The procedure of selecting an appropriate statistical analysis for a replicate study design was predefined in the study protocol. RESULTS: The 90% confidence intervals (CI) were calculated for the area under the time-concentration curve (AUC), maximum concentration (C(max)) and the time to reach C(max) (t(max)) of test/reference drug ratios for a bioequivalence range from 0.80-1.25. The mean test/reference drug ratios were completely within the 90% CIs with values of 1.041 (CI: 0.892-1.216), 1.021 (CI: 0.913-1.140) and 1.068 (CI: 0.914-1.249) for AUC(0-14 h), C(max) and t(max), respectively. CONCLUSION: The rate and the extent of intranasal desmopressin absorption are identical for both study preparations. Thus, the desmopressin test preparation met all equivalence criteria and thereby was proven bioequivalent with a marketed reference nasal desmopressin spray.

Administration, Intranasal↗
PubMed2003

Gene expression profiling of ciliary neurotrophic factor-overexpressing rat striatal progenitor cells (ST14A) indicates improved stress response during the early stage of differentiation.

Neuronal progenitor cells delivering neurotrophic factors are a promising therapeutic tool for treatment of neurodegenerative diseases. Although several promising results have come from studies in different animal models, detailed knowledge of the action of neurotrophic factors in the CNS is still lacking. A clonally derived, immortalized rat striatal cell line (ST14A) expressing ciliary neurotrophic factor (CNTF) offers a stable and controlled background with which to analyze CNTF actions on the transcriptional level in CNS progenitor cells. To identify early transcriptional changes induced by CNTF expression, we transfected the CNTF gene into ST14A cells, which differentiate at the nonpermissive temperature of 39 degrees C via suppression of the immortalizing SV40 large T antigen. This shows a CNTF-dependent hypoxic/ischemic stress response during the earliest stage of differentiation, with expression of specific transcripts and evidence of translational repression leading to decreased protein synthesis in the transfected cells. This process is mediated by the Ras/MAP kinase pathway and is accompanied by impaired proliferation and metabolism as well as signs of neuronal differentiation. The stress-like response in the early stage of differentiation improves the ability of the transfected cells to respond to and cope with a stressful environment in vivo. The present data indicate higher viability, longer life, and greater differentiation capacity of CNTF-ST14A cells if they are used for transplantation. We conclude that the stress-like response during the early stage of differentiation improves the ability of the CNTF-ST14A cells to respond and adapt to a stressful environment, which renders them useful candidate cells for in vivo trials of treatment for neurodegenerative diseases in animal models, e.g., of Huntington's disease.

Animals↗
PubMed2003

Issues in designing flexible trials.

We outline the general framework of adaptive combination tests and discuss their relationship to flexible group sequential designs. An important field of applications is sample size reassessment. We discuss reassessment rules based on conditional power arguments using either the observed or the prefixed effect size. These rules tend to lead to large expected sample sizes for small actual effects. However, the application of a maximal bound for the second stage sample size leads to more favourable properties. Additionally, we consider an optimized reassessment rule in terms of expected sample sizes. Since the adaptive design does not use the classical test statistics for some types of sample size reassessments, the adaptive test may reject the null hypothesis while the classical one-sample test does not. We characterize sample size reassessment rules, where such inconsistencies are avoided. Finally, the extension of flexibility to the number of stages is explored. In the first interim analysis a second interim analysis is only planned if the chance to achieve a decision there is high. This leads to savings in the average number of interim analysis performed, without paying a noticeable price in terms of expected sample size.

Clinical Trials as Topic↗
PubMed2003

Ciliary neurotrophic factor overexpression in neural progenitor cells (ST14A) increases proliferation, metabolic activity, and resistance to stress during differentiation.

Neurotrophic factors exert considerable neuroprotective and neurorestorative effects in neurodegenerative diseases. Because neuronal progenitor cells have, at least in part, the potency to restore degenerated neuronal networks, transgenic high-dosage expression of neurotrophins by these cells in neurotransplantation may be advantageous. In the present study, a retroviral vector containing the gene of rat ciliary neurotrophic factor (rCNTF) was permanently transfected into a striatal neuronal progenitor cell line. Qualitative and quantitative analyses demonstrated a sustained expression of the transgene; i.e., rCNTF was present at the mRNA level and protein level. Moreover, cocultivation in separate chambers of transgenic CNTF-ST14A cells and CNTF-dependent TF1 cells exerted typical biological effects, such as increased proliferation and differentiation of the TF1 cells, indicating the functional integrity of the secreted recombinant neurotrophin. The CNTF-ST14A cells displayed improved stress response compared with native ST14A cells under differentiation conditions, i.e., at the nonpermissive temperature of 39 degrees C and after staurosporine exposure, respectively. This effect coincided with a relatively reduced apoptosis rate and a raised metabolic activity of CNTF-ST14A cells at 39 degrees C. Neurotransplantation of CNTF-ST14A cells in the rat quinolinic acid model of Huntington's disease showed a significant and sustained decline in pathological apomorphine-induced rotations compared with parental ST14A cells. We conclude that sustained functional transgene CNTF production improves stress response as well as metabolic activity, making CNTF-ST14A cells a promising tool for neurotransplantation in the quinolinic acid model of Huntington's disease.

Animals↗
PubMed2003

Frequency and phenotypic variability of the GAG deletion of the DYT1 gene in an unselected group of patients with dystonia.

BACKGROUND: Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained muscle contractions affecting one or more sites of the body, frequently causing twisting and repetitive movements or abnormal postures. A 3-base pair (GAG) deletion in the DYT1 gene is held responsible for most cases of early-onset primary generalized dystonia in the Ashkenazi Jewish population as well as in non-Jewish patients. OBJECTIVES: To investigate the prevalence of the GAG deletion in the DYT1 gene and the phenotypic variability in the general population by testing patients with different subtypes of dystonia from 4 different movement disorder outpatient clinics in Germany. METHODS: Two hundred fifty-six patients were tested for the GAG deletion mutation in the DYT1 gene by means of published primers and polymerase chain reaction amplification to determine GAG deletion status. RESULTS: Six of the 256 patients did carry the GAG-deletion in the DYT1 gene. However, only 2 of the 6 mutation carriers presented with what is thought to represent classic features of early-onset primary generalized dystonia. The DYT1 mutation was also detected in 2 patients with multifocal dystonia, 1 of them presenting with involvement of cranial and cervical muscles, and in 2 patients with writer's cramp of both hands with only slight progression. Our findings demonstrate that the mutation may be associated with not only generalized but also segmental and multifocal forms of dystonia. CONCLUSIONS: Our data underline the wide range of phenotypic variability of the DYT1 mutation. A priori prediction of the mutation carrier status in dystonic patients and genetic counseling of affected families with respect to the clinical manifestation may prove difficult.

Base Pairing↗
PubMed2003

Do CTG expansions at the SCA8 locus cause ataxia?

To evaluate the significance of expanded CTG repeats at the SCA8 locus, we analyzed the allele distribution in 1,262 German ataxia patients. We found intermediate and expanded CTG repeats with similar frequencies in ataxia patients with and without established genetic diseases. One family linked to the SCA8 locus showed incomplete penetrance and an association of smaller CTG repeats with more severe disease. Our data question the disease-causing character of CTG expansions for SCA8 and advise great caution in genetic testing.

Adult↗