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Biomedical subjects

K Berger

Publications and source records attributed to K Berger.

At least 55 records · Page 3Linked to original sources

Double-blind crossover trial of trimethoprim-sulfamethoxazole in spinocerebellar ataxia type 3/Machado-Joseph disease.

OBJECTIVE: To evaluate the efficiency of a combination of trimethoprim and sulfamethoxazole in patients with spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). DESIGN: Placebo-controlled, double-blind crossover trial in 22 patients with genetically confirmed SCA3/MJD. Study phases of 6 months were separated by a washout period of 4 weeks. Dosages were a combination of trimethoprim, 160 mg, and sulfamethoxazole, 800 mg, twice daily for 2 weeks, followed by a combination of trimethoprim, 80 mg, and sulfamethoxazole, 400 mg, twice daily for 5.5 months. SETTING: Outpatient department of the Neurological Clinic, Ruhr-University, Bochum, Germany. MAIN OUTCOME MEASURES: Ataxia ranking scale, self-assessment score, static posturography, and results of motor performance testing. Effects on the visual system were studied using the achromatic Vision Contrast Test System and the Farnsworth-Munsell 100-hue test for color discrimination. Physical and mental health were documented using the Medical Outcomes Study 36-Item Short-Form Health Survey. Subgroup analyses assessed the influence of age, sex, age at onset, duration of the disease, phenotype, and CAG repeat length on test performance. RESULTS: Twenty of 22 patients completed the study. Dropouts were due to a rash (placebo phase) and an attempted suicide in a family conflict. Trimethoprim-sulfamethoxazole therapy had no significant effect in SCA3/MJD patients in the short-term analysis (2 weeks) or in the long-term interval (6 months). CONCLUSIONS: In contrast to previous reports that studied smaller groups of patients, treatment with trimethoprim-sulfamethoxazole did not improve the diverse and complex movement disorders caused by SCA3/MJD. Trimethoprim-sulfamethoxazole had no effect on the visual system and cannot be recommended as a continuous treatment for SCA3/MJD patients.

Adult↗

[Patient assaults of staff; a prospective study of the incidence, circumstances and sequelae].

Patient assaults in psychiatric hospitals result in a considerable number of job-related accidents and personnel absenteeism. The aim of this study was to assess the incidence of assaults, analyze trigger situations, and describe physical and psychological consequences among staff members. Within a study period of 6 months, all apparently aggressive physical contacts between patients and staff in six northwest German psychiatric hospitals were assessed. Patient and staff variables, situational characteristics, and physical as well as psychological consequences were evaluated. During this time, 155 assaults on 170 staff members were reported. Before the assaults, most of the patients showed early signs of aggression as an indication of situational worsening. Work absenteeism following the assaults was observed in 5% of the affected staff. In 14%, symptoms of post-traumatic stress could be diagnosed using the questionnaire version of the PTSD interview. In conclusion, the study results suggest that additional training of younger personnel and implementation of conflict management schemes could help to prevent these assaults.

Accidents, Occupational↗

The association of dopamine agonists with daytime sleepiness, sleep problems and quality of life in patients with Parkinson's disease--a prospective study.

OBJECTIVE: Reports that dopamine agonists (DA) precipitate sudden daytime sleep episodes in Parkinson's disease (PD) patients have received widespread attention. It remains unclear if non-ergoline and ergoline DAs have differential sedating effects or if sedation rather represents a class effect of DAs. The aim of this study was the evaluation of sleep disturbances and the quality of life (QoL) in PD patients with different dopaminergic treatment strategies. PATIENTS AND METHODS: This analysis is part of the FAQT-study, a prospective German cohort study evaluating determinants of QoL in PD patients. A subgroup of 111 PD patients was evaluated twice, at baseline and after one year of follow-up, using standardised and validated questionnaires (Unified Parkinson's disease rating scale (UPDRS), Hoehn and Yahr classification, Center for Epidemiologic Studies Depression Scale (CESD), Short Form-36 (SF-36), Parkinson Disease Questionnaire (PDQ-39)). The impact of treatment strategies on sleep problems, daytime sleepiness, bad dreams and hallucinations, depression and QoL in PD patients was analysed separately for ergoline DAs, non-ergoline DAs and the patient group taking no DA. RESULTS: At baseline, sleep problems were reported by about one third of the patients with and without DA medication. Excessive daytime sleepiness (EDS) was higher in the two DA groups (ergoline 11.9%, non-ergoline 9.1%) than among patients not taking DAs (4.5 %). At follow-up, sleep problems in general had decreased among patients taking DAs continuously and among those newly taking DAs, while the sleep problems increased in patients discontinuing DAs. However, EDS had increased to 25% in patients newly taking DAs, and decreased to 15.9% in those taking them continuously. QoL scores at follow-up were slightly increased in the patient groups newly taking and discontinuing DAs (the latter except in physical functioning) while those on continuing DA-medication remained unchanged. CONCLUSION: No differential effects of ergoline or non-ergoline DAs on sleep problems were found. Different dopaminergic treatment strategies did not influence QoL. Our results support the evidence that sedation may be rather a class effect of DAs.

Aged↗

Ingestion of toxic Microcystis aeruginosa by dairy cattle and the implications for microcystin contamination of milk.

Microcystin (MCYST) toxins can be produced by the bloom-forming cyanobacterium Microcystis aeruginosa. They are chemically stable compounds and have both acute and chronic effects on the health of mammals, including cattle and humans. Cattle will drink water containing lethal cell concentrations of M. aeruginosa. When cattle consume sub-lethal doses of microcystins, the fate of those toxins is unknown. We provided drinking water containing 1 x 10(5) cells ml(-1) M. aeruginosa (strain MASH01-A19) to four lactating Holstein-Friesian dairy cattle for 21 days to determine if MCYST-LR produced by the cyanobacteria, could be detected in milk produced by the cattle. Cattle consumed up to 15 mg MCYST-LR at an ingestion rate of 1.21 microg kg (live weight) d(-1). Analysis by HPLC and ELISA indicated that no detectable amounts of microcystin from the cyanobacteria were present in the milk obtained from the treated animals. Based on the level of quantitation of the ELISA analyses, the maximum possible concentration in the milk was less than 2 ng l(-1). This is more than three orders of magnitude less that the concentration that could be considered problematic for milk of 0.86 microg l(-1) which we calculated using the World Health Organization derived tolerable daily intake for MCYST-LR and the per capita daily consumption of milk in Australia.

Animals↗

Economic impact of community- and nosocomially acquired rotavirus gastroenteritis in Austria.

OBJECTIVE: To determine the average costs per child for rotavirus (RV) acute gastroenteritis from different perspectives, from the hospital's, third-party payer's, pediatrician's and family's perspectives as well as in summary from the societal one. MATERIALS AND METHODS: This cost-of-illness study is based on data collected alongside a 6-month prospective, laboratory-confirmed epidemiologic study that evaluated the disease burden of RV infection in Austrian children < or =48 months of age. The study population at risk to contract a community- and nosocomially acquired acute gastroenteritis comprised 9,687 children. All of the 51 children with community-acquired and 33 with nosocomially acquired RV acute gastroenteritis were included in this analysis. The annual costs were estimated by means of extrapolation. RESULTS: For community-acquired RV acute gastroenteritis, the average costs from the hospital's perspective were EURO (EUR) 97.8, from the third party payer's perspective 95.6 EUR, followed by 29.9 EUR and 9.8 EUR from the family's and pediatrician's perspectives, respectively. For nosocomially acquired RV acute gastroenteritis the average costs from the hospital's perspective were 1,494 EUR and from the third party payer's and family's perspectives 831 EUR and 116.8 EUR, respectively. In summary the average costs from the societal point of view for community-acquired RV acute gastroenteritis were 250 EUR and for nosocomial infections 2,442 EUR. After extrapolation the estimated total annual costs were 7.17 EUR million to 0.97 EUR million (13.6%) caused by community-acquired RV acute gastroenteritis and 6.2 EUR million (86.4%) caused by nosocomial RV acute gastroenteritis. CONCLUSION: This cost-of-illness study clearly demonstrates the great impact of RV acute gastroenteritis, mainly of nosocomially acquired infection, on medical health care costs in Austria. To cut costs efforts in disease prevention should be encouraged.

Austria↗

Health-related quality of life and healthcare utilisation in patients with Parkinson's disease: impact of motor fluctuations and dyskinesias.

Idiopathic Parkinson's disease (PD) is a common chronic progressive neuro-degenerative disorder associated with the progressive loss of dopaminergic neurons in the substantia nigra. The natural course of the disease may lead to severe disability despite a variety of pharmacological and surgical treatment options. Levodopa is still the most effective symptomatic treatment for PD; however, long term use can cause a number of adverse effects including motor complications, nausea and vomiting, postural hypotension and changes in mental status. The onset of motor complications marks a crucial point in the management of PD. They may present as changes between akinetic and mobile phases (motor fluctuations) or as abnormal involuntary movements (dyskinesias). After levodopa treatment for 3 to 5 years, motor complications occur in approximately 50% of patients, and after 10 years in >80% of patients. Treatment options have recently expanded as new drugs have been licensed and surgical procedures refined. Patients with motor complications present a demanding task in disease management, and often multiple drugs and high dosages are necessary to achieve only suboptimal control, resulting in increased healthcare utilisation. Costs increase considerably in patients with motor fluctuations and dyskinesias compared with patients without these symptoms. In a French study, 6-month direct medical costs per patient increased from 1648 euros (EUR) to EUR3028 in patients without and with motor fluctuations, respectively. In a recent French study a significant difference in monthly direct medical costs was found in patients with and without dyskinesias (EUR560 vs 170). Unfortunately, no data are available on the effect of motor complications on indirect costs. Several studies have shown that health-related quality of life (HR-QOL) is reduced when motor fluctuations occur. This may also be true of dyskinesias, but because of the limited number of studies a definite conclusion is not yet possible. Recently, surgical treatment options have been used to deal with advanced PD and late stage complications. Although their effect on motor complications and HR-QOL is well documented, they result in increased costs (total medical cost: EUR28920) compared with drug treatment alone and are increasingly restricted by healthcare providers. The purpose of this article is to review the available data from pharmacotherapeutic. surgical and economic studies on HR-QOL and healthcare expenditure in patients with PD, with a major focus on the impact of motor fluctuations and dyskinesias.

Aged↗

Genetic analysis of the alpha2-macroglobulin gene in early- and late-onset Parkinson's disease.

Recent association studies investigating polymorphisms in the alpha2-macroglobulin (A2M) gene provided evidence for an involvement of this protease inhibitor in the pathogenesis of Alzheimer's disease (AD). The partially overlapping pathology between AD and Parkinson's disease (PD) led us to investigate the role of A2M in PD. We performed association studies in a large sample of 328 German PD patients and 322 closely matched healthy controls. Analyzing the Val1000Ile polymorphism and a pentanucleotide deletion in the 5' splice site of exon 18 of the A2M gene we found an excess of homozygosity for the A2M deletion in early-onset PD (EOPD) patients (age at onset < 50 years) compared to late-onset PD (LOPD) patients (age at onset > 50 years; p = 0.008, p(p)c = 0.064, chi2 = 7.017). Therefore our data might indicate an age at onset modulating effect of the homozygous A2M deletion in PD.

Age of Onset↗

Mutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients.

Recently, an Ile93Met substitution has been identified in the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene in a single German PD family with autosomal dominant inheritance. To determine whether mutations in the UCHL1 gene are causative for Parkinson's disease (PD) a detailed mutation analysis was performed in a large sample of German sporadic and familial PD patients. We found no disease-causing mutation in the coding region of the UCHL1 gene. Direct sequencing revealed six intronic polymorphisms in the UCHL1 gene. Analysis of an S18Y polymorphism in exon 3 of the UCHL1 gene in sporadic PD patients and controls showed carriers of allele 2 (tyrosine) significantly less frequent in patients with a reduced risk of 0.57 (CI = 0.36-0.88; p = 0.012, p(c) = 0.047, chi2 = 6.31). Our study shows that sequence variations in the coding region of UCHL1 are a rare event. A protective effect of a certain UCHL1 variant in the pathogenesis of sporadic PD is suggested, underlining the relevance of UCHL1 in neurodegeneration.

Aged↗

[Knowledge about stroke among the German population].

BACKGROUND AND OBJECTIVE: Modern stroke therapy requires patients to correctly identify stroke symptoms and seek immediate hospital admission. US studies showed that only 57% of the population knew at least one stroke symptom. This is the first study about stroke knowledge among German populations. METHODS: Using a cross-sectional questionnaire survey, 300 working-age participants of the PROCAM study, the Prospective Cardiovascular Münster Study, and 95 senior citizens of the Augsburg Study, a follow-up project of the MONICA survey 1989/90, were asked about stroke symptoms and what to do if they occur. Good knowledge about stroke was defined as knowing at least two stroke symptoms and calling the emergency medical system or seeking immediate hospital admission in case of symptoms. RESULTS: Participation rate in the PROCAM study was 90%, while all senior citizens took part. The mean age of the working population was 41.2 years, the mean age of the retired population was 72.8 years. 35% of the working and 24.5% of the retired participants knew at least two stroke symptoms. Urgent hospital admission was selected by 78.2% of the occupational but only 41.5% of the retired participants. Good stroke knowledge was demonstrated by nearly a third of the workers but less than 10% of the elderly. Among the occupational population, being a white-collar worker or knowing someone with a stroke was a significant predictor of good stroke knowledge. Among senior citizens higher age and current smoking status were significant predictors. CONCLUSION: Our study shows significant information deficits about stroke in our population: education needs to be geared especially towards the elderly.

Adult↗

Prevalence and risk factors of RLS in an elderly population: the MEMO study. Memory and Morbidity in Augsburg Elderly.

OBJECTIVE: To evaluate prevalence, sociodemographic characteristics, and risk factors of restless legs syndrome (RLS) in a population-based survey of the elderly, using standard diagnostic criteria. BACKGROUND: Population-based studies of RLS are rare and have not yet used standard definition criteria. METHODS: The Memory and Morbidity in Augsburg Elderly (MEMO) Study is a follow-up project of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Survey-Augsburg, Germany, 1989-1990, evaluating neurologic diseases and their risk factors in a German population 65 to 83 years of age. Two RLS-trained physicians assessed the prevalence of RLS based on the four minimal standard criteria (International Restless Legs Syndrome Study Group, 1995) using standardized questions in face-to-face interviews. They also obtained information on medical history, medications, depression (Center of Epidemiologic Studies Depression Scale), and quality of life (Short Form 36) and performed a standardized neurologic examination for each participant. RESULTS: The study population included 369 participants (173 women and 196 men). The overall prevalence of RLS was 9.8% (n = 36) and higher in women (13.9% versus 6.1%; p = 0.02). In women, the prevalence did not change with age, whereas men showed a nonsignificant inverse trend with increasing age. RLS-positive individuals took more benzodiazepines and estrogen compared with non-RLS cases, but the differences were not statistically significant. Participants with RLS had higher incidence of depression (p = 0.012) and lower self-reported mental health scores (p = 0.029) than did non-RLS cases. CONCLUSIONS: RLS is a frequent syndrome in the elderly with considerable impact on self-perceived mental health, affecting women about twice as often as men.

Aged↗

[Cost effectiveness of pravastatin in secondary coronary prevention in patients with myocardial infarct or unstable angina in Germany. An analysis on the basis of the LIPID trial].

Secondary coronary prevention with lipid lowering drugs has become a major issue in health policy formulation due to the large upfront investment in drug therapy. The recently completed LIPID trial with pravastatin in secondary prevention immediately raise the question whether pravastatin might be cost-effective in Germany. We conducted a cost-effectiveness analysis from the perspective of third party payers. The following costs were included in the analysis: daily treatment costs of pravastatin, non-fatal myocardial infarction, coronary bypass operations and stroke. Life years gained were obtained by applying the declining exponential approximation of life expectancy. All calculations were standardized to 1,000 treated patients. The net costs of treating 1,000 patients (i.e. drug costs minus the costs of sequelae and interventions) are DM 8.4 Mio. In addition, a total of 405 life years may be saved through treatment. The corresponding cost-effectiveness of pravastatin treatment is DM 20,674,-(DM 17,314,-, discounted by 3% p.a.).

Angina, Unstable↗

The economic burden of hepatitis B in Germany.

Despite the widespread distribution of Hepatitis B virus (HBV) infection and the ongoing controversy about HBV immunization, surprisingly few published studies examined in detail the economic impact of HBV infection in Europe. Therefore, we investigated a cohort of 180 patients throughout Germany to evaluate the economic burden of HBV-associated disease. In 58 patients with acute and 122 patients with chronic HBV infection, cost-consuming events including direct medical costs and work-loss costs were documented. The direct costs were DM 7702 (95% confidence interval (CI): 5473-9931) for each acute HBV infection and DM 4247 (CI: 1601-6893) per patient-year of chronic HBV infection, with marked differences between different stages of HBV disease. The derived overall costs (1997 price levels) per year were DM 10,018 (CI: 7613-12,421) and DM 4860 (CI: 2185-7536), respectively. Based on crude population-based estimates (30,000 acute and 420,000 chronic HBV cases), we calculated the total HBV-related costs in Germany to exceed DM 1200 millions in 1997 (CI: 924.2-1536.7), with the treatment of patients with chronic active HBV disease as the major cost determinant. Previously published data from Germany probably overestimated the financial impact of acute HBV infection. In summary, our results illustrate the ongoing economic importance of this potentially life-threatening, but preventable disease and support the call for more accurate HBV surveillance and control in Germany.

Adult↗

[Quality assurance in treatment of stroke: basic module of the German Stroke Registry Study Group].

BACKGROUND AND PURPOSE: Comparable, standardised data on the quality and efficiency of stroke care in Germany are lacking. The Arbeitsgemeinschaft Deutscher Schlaganfall-Register (ADSR--German Stroke Registries Study Group) has defined a "Minimum DataSet" for the evaluation of quality indicators of stroke treatment in Germany. METHODS: The ADSR is a voluntary network of current regional stroke registries aiming at a standardisation in the use of stroke terminology and methods of data collection for German stroke databases. Currently six regional stroke registries are cooperating in the ADSR, combining data from about 18,000 stroke patients in 110 hospitals annually. RESULTS: In the design of the ADSR DataSet a modular approach was chosen. The ADSR "Minimum DataSet" was adapted for a wide use in different health care facilities. In addition to the "Minimum DataSet" an "Advanced DataSet" will be developed to document additional items of stroke care in specialised stroke centres. The ADSR DataSet collection will be completed by special "Extended DataSets", designed for answering centre-specific and research questions. CONCLUSION: The ADSR "Minimum DataSet" allows a standardised assessment of stroke care in Germany. It is the first questionnaire that provides valid and reliable comparisons between different clinical settings as well as regional stroke databases. The ADSR "Minimum DataSet" defines core items for a future National German Health Report on stroke care.

Data Collection↗

Evaluation of hepatitis C virus glycoprotein E2 for vaccine design: an endoplasmic reticulum-retained recombinant protein is superior to secreted recombinant protein and DNA-based vaccine candidates.

Hepatitis C virus (HCV) is the leading causative agent of blood-borne chronic hepatitis and is the target of intensive vaccine research. The virus genome encodes a number of structural and nonstructural antigens which could be used in a subunit vaccine. The HCV envelope glycoprotein E2 has recently been shown to bind CD81 on human cells and therefore is a prime candidate for inclusion in any such vaccine. The experiments presented here assessed the optimal form of HCV E2 antigen from the perspective of antibody generation. The quality of recombinant E2 protein was evaluated by both the capacity to bind its putative receptor CD81 on human cells and the ability to elicit antibodies that inhibited this binding (NOB antibodies). We show that truncated E2 proteins expressed in mammalian cells bind with high efficiency to human cells and elicit NOB antibodies in guinea pigs only when purified from the core-glycosylated intracellular fraction, whereas the complex-glycosylated secreted fraction does not bind and elicits no NOB antibodies. We also show that carbohydrate moieties are not necessary for E2 binding to human cells and that only the monomeric nonaggregated fraction can bind to CD81. Moreover, comparing recombinant intracellular E2 protein to several E2-encoding DNA vaccines in mice, we found that protein immunization is superior to DNA in both the quantity and quality of the antibody response elicited. Together, our data suggest that to elicit antibodies aimed at blocking HCV binding to CD81 on human cells, the antigen of choice is a mammalian cell-expressed, monomeric E2 protein purified from the intracellular fraction.

Animals↗

Effect of high-fat diet, surrounding temperature, and enterostatin on uncoupling protein gene expression.

Nonshivering thermogenesis induced in brown adipose tissue (BAT) during high-fat feeding is mediated through uncoupling protein 1 (UCP1). UCP2 is a recently identified homologue found in many tissues. To determine the role of UCP1 and UCP2 in thermoregulation and energy balance, we investigated the long-term effect of high-fat feeding on mRNA levels in mice at two different ambient temperatures. We also treated mice with the anorectic peptide enterostatin and compared mRNA levels in BAT, white adipose tissue (WAT), stomach, and duodenum. Here, we report that high-fat feeding at 23 degrees C increased UCP1 and UCP2 levels in BAT four- and threefold, respectively, and increased UCP2 levels fourfold in WAT. However, at 29 degrees C, UCP1 decreased, whereas UCP2 remained unchanged in BAT and increased twofold in WAT. Enterostatin increased UCP1 and decreased UCP2 mRNA in BAT. In stomach and duodenum, high-fat feeding decreased UCP2 mRNA, whereas enterostatin increased it. Our results suggest that the regulation of uncoupling protein mRNA levels by high-fat feeding is dependent on ambient temperature and that enterostatin is able to modulate it.

Adipose Tissue↗

Prevalence of Parkinson's disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group.

The results of seven population-based studies were examined separately and pooled to obtain age- and sex-specific estimates of the prevalence of PD. An in-person screening instrument and diagnostic clinical examination were used to detect potential PD cases. The overall prevalence (per 100 population) in persons 65 years of age and older was 1.8, with an increase from 0.6 for those age 65 to 69 years to 2.6 for those 85 to 89 years. There were no sex differences in prevalence of PD.

Age Factors↗