Patterns of instability of expanded CAG repeats at the ERDA1 locus in general populations.
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A highly polymorphic CAG repeat locus, ERDA1, was recently described on human chromosome 17q21.3, with alleles as large as 50-90 repeats and without any disease association in the general population. We have studied allelic distribution at this locus in five human populations and have characterized the mutational patterns by direct observation of 731 meioses. The data show that large alleles (>/=40 CAG repeats) are generally most common in Asian populations, less common in populations of European ancestry, and least common among Africans. We have observed a high intergenerational instability (46. 3%+/-5.1%) of the large alleles. Although the mutation rate is not dependent on parental sex, paternal transmissions have predominantly resulted in contractions, whereas maternal transmissions have yielded expansions. Within this class of large alleles, the mutation rate increases concomitantly with increasing allele size, but the magnitude of repeat size change does not depend on the size of the progenitor allele. Sequencing of specific alleles reveals that the intermediate-sized alleles (30-40 repeats) have CAT/CAC interruptions within the CAG-repeat array. These results indicate that expansion and instability of trinucleotide repeats are not exclusively disease-associated phenomena. The implications of the existence of massively expanded alleles in the general populations are not yet understood. (+info)
Validity of interpretation criteria for standardized Western blots (immunoblots) for serodiagnosis of Lyme borreliosis based on sera collected throughout Europe.
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Western blotting (WB; immunoblotting) is a widely used tool for the serodiagnosis of Lyme borreliosis (LB), but so far, no generally accepted criteria for performance and interpretation have been established in Europe. The current study was preceeded by a detailed analysis of WB with whole-cell lysates of three species of Borrelia burgdorferi sensu lato (U. Hauser, G. Lehnert, R. Lobentanzer, and B. Wilske, J. Clin. Microbiol. 35:1433-1444, 1997). In that study, interpretation criteria for a positive WB result were developed with the data for 330 serum samples (from patients with LB in different stages [n = 189] and from a control group [n = 141]) originating mostly from southern Germany. In the present work, the interpretation criteria for strains PKo (Borrelia afzelii) and PBi (Borrelia garinii) developed in the previous study were reevaluated with 224 serum samples (from patients with LB in different stages [n = 97] and from a control group [n = 127]) originating from throughout Europe that were provided by the European Union Concerted Action on Lyme Borreliosis (EUCALB). De novo criteria were developed on the basis of the reactivities of the EUCALB sera and were evaluated with the data for the samples from southern Germany. Comparison of all results led to the following recommendations: For WB for immunoglobulin G (IgG), at least two bands among p83/100, p58, p43, p39, p30, OspC, p21, p17, and p14 for PKo and at least one band among p83/100, p39, p30, OspC, p21, and p17b for PBi; for WB for IgM, at least one band among p39, OspC, and p17 or a strong p41 band for PKo and at least one band among p39 and OspC or a strong p41 band for PBi. WB with PKo was the most sensitive, and this strain is recommended for use in WB for the serodiagnosis of LB throughout Europe. (+info)
Typhoid fever due to Salmonella Kapemba infection in an otherwise healthy middle-aged man.
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We report the case of a patient with a Salmonella Kapemba infection, who suffered, 3 weeks after a holiday in Israel, occurrences of high fever and lower back pain for 10 days and icterus for 2 days before admission. Laboratory findings revealed a slight cholestasis and elevation of acute phase protein levels. In the blood culture a Salmonella Kapemba-type organism was cultured. The patient was afebrile for 10 days after hospitalization and then suddenly developed a temperature of 40 degrees C again. At the same time leukopenia, thrombocytopenia, and a rise of D-dimer levels were detected. The patient was admitted to the intensive care unit for a few days, because a disseminated intravascular coagulation was suspected. With magnetic resonance imaging and bone scintigraphy no osteomyelitis or abscess formation could be found. A transesophageal ultrasonography of the heart revealed no signs of endocarditis. In multiple stool cultures no salmonellas could be detected. After antibiotic treatment with ciprofloxacin the fever and lower back pain subsided, and the patient was discharged a fortnight later. This is the first reported case of typhoid fever due to the bacterium Salmonella Kapemba. (+info)
Screening for mutations in the promoter and the coding region of the IGFBP1 and IGFBP3 genes in Silver-Russell syndrome patients.
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In the present study we sought to identify genetic variation in genes for insulin-like growth factor binding proteins 1 and 3 (IGFBP1, IGFBP3) in 7p12-13 which through alteration of protein function or level of expression might contribute to the manifestation of Silver-Russell syndrome. Genomic DNA samples from 49 Silver-Russell syndrome (SRS) patients and from unaffected controls were investigated by single-strand conformation analysis. Overlapping polymerase chain reaction fragments covered the whole coding sequences as well as the 5' untranslated region of the IGFBP1 and IGFBP3 genes. We detected 3 new polymorphisms in the transcribed sequence of IGFBP1, one amino acid polymorphism in exon 1 of IGFBP3 and four variants in its promotor region and in intron 1. They all occurred in similar frequencies in SRS patients and in controls. Thus, paternally inherited mutations in the promoter and coding regions of IGFBP1 and IGFBP3 genes play neither a major nor a minor role in the etiology of SRS. The newly detected polymorphisms in the coding region are powerful tools for analysis of imprinting status and for detection of possible changes in the imprinting patterns of the two genes. (+info)
Familial burning feet syndrome inherited as an autosomal dominant trait has been described in only one family. Due to an associated sensory neuropathy the autosomal dominant burning feet syndrome was suggested to represent a variant form of hereditary sensory and autonomic neuropathy type I (HSAN I). Clinical, histopathological, and molecular genetic studies were performed in a large German kindred with autosomal dominant burning feet syndrome. The autosomal dominant burning feet syndrome was associated with a neuropathy predominantly affecting small unmyelinated nerve fibres. Linkage to the HSAN I locus on chromosome 9q22 and to the Charcot-Marie-Tooth disease type 2B (CMT 2B) locus on chromosome 3q13-q22 was excluded. The autosomal dominant burning feet syndrome is neither allelic to HSAN I nor to CMT 2B and thus represents a distinct genetic entity. (+info)
The carnage wrought by major economic change: ecological study of traffic related mortality and the reunification of Germany.
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OBJECTIVE: To document the effects of sudden economic change on death rates for occupants of cars in the former German Democratic Republic (East Germany). DESIGN: Ecological time series study of East Germany in comparison with the former Federal Republic of Germany (West Germany) before and after reunification in 1990. SETTING: East and West Germany from 1985 to 1996. SUBJECTS: Populations of East and West Germany between 1985 and 1996. MAIN OUTCOME MEASURES: Death rates for occupants of cars. RESULTS: After the reunification of Germany, East Germany experienced a sudden, temporary affluence and a concomitant fourfold increase in death rates for car occupants between 1989 and 1991. Although death rates increased in all age groups, young adults (aged 18-24) were most affected. The death rate per 100 000 population for those aged 18-20 years increased 11-fold between 1989 and 1991; for those aged 21-24 years the increase was eightfold. CONCLUSION: A tragic consequence of the reunification of Germany was a dramatic increase in the death rate for car occupants. Sudden economic change and availability of cars resulted in both a rise in vehicle ownership and an increase in the number of inexperienced drivers on roads that were ill prepared for the increased traffic. The lesson learnt from Germany is that during times of economic change and modernisation, measures to prevent the predictable injury deaths that will result need to be considered. (+info)
A double-blind, randomized, multicentre, crossover study to prove equivalence of pancreatin minimicrospheres versus microspheres in exocrine pancreatic insufficiency.
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BACKGROUND: Modern pancreatin preparations consist of enteric-coated microspheres to protect the enzymes from gastric acid. There are, however, no clinical trials comparing different sizes of pancreatin microspheres with regard to fat excretion and fat intake. AIM: To prove both equivalent efficacy and safety of conventional pancreatin microspheres and smaller pancreatin minimicrospheres in patients with exocrine insufficiency due to chronic pancreatitis. METHODS: In this prospective, randomized, double-blind, multicentre, crossover trial, patients with a stool fat excretion of > 7.5 g/day during a placebo period were randomly assigned either to the minimicrosphere/microsphere treatment sequence or vice versa. The primary end-point was the coefficient of fat absorption, which was calculated from fat excretion and fat intake during the course of a standardized diet. Stool weight, clinical symptoms and the safety of the preparations were also evaluated. RESULTS: Thirty-seven patients entered the study, of whom 23 fulfilled the criteria for the crossover period. In the per protocol analysis (n=18), the 90% confidence intervals for the coefficient of fat absorption of both crossover periods lay entirely within the equivalence range (P=0.02). The intention-to-treat analysis revealed similar results, but the equivalence range was slightly missed (P=0.07). Similar results were obtained for the secondary parameters and the reported adverse events. CONCLUSIONS: Pancreatin minimicrospheres have been shown to be equally effective as microspheres in improving the coefficient of fat absorption in patients with exocrine insufficiency due to chronic pancreatitis. (+info)
'Manacled competition': market reforms in German health care.
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In 1993 Germany joined the small but swelling ranks of societies determined to explore managed competition as a means of slowing the growth of health spending by giving stakeholders new incentives for efficiency. Realizing the benefits of competition, however, demands changes in institutional norms and regulatory practices that now largely handcuff those who would follow competitive logic into "managed care." In time Germany's system of "manacled competition" may evolve into a happy higher synthesis of managed care and managed competition. Or policymakers may conclude that the political price of installing workable market forces in health care is too high and reconcile themselves to more traditional applications of political pressure. (+info)