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Biomedical subjects

A Baumgartner

Publications and source records attributed to A Baumgartner.

At least 19 recordsLinked to original sources

Antimicrobial resistance of Yersinia enterocolitica strains from human patients, pigs and retail pork in Switzerland.

To obtain basic data for future resistance monitoring programs, 386 Yersinia enterocolitica strains from human patients, raw retail pork and pig feces were tested for their susceptibilities to 16 antimicrobial agents and two antimicrobial growth promoters (carbadox and olaquindox). No strains were resistant to ceftriaxone, cefuroxime, ciprofloxacine, gentamicin, kanamycin, neomycin or polymyxin. Although in Switzerland carbadox and olaquindox were used as growth promoters for pigs for over 25 years, all strains were susceptible to them. In contrast, there were high levels of resistance to ampicillin, cefalothin and amoxicillin/clavulanic acid. Less than 10% of clinical isolates and strains from pig feces were resistant to streptomycin, sulfonamide, trimethoprim/sulfamethoxazole, tetracyclin, trimethoprim and chloramphenicol, but strains from retail pork were all susceptible to these antimicrobial agents. This finding suggested that pork is probably not a major source of Y. enterocolitica that cause human infections in Switzerland. A difference between clinical isolates and strains from pork was also shown by serotyping. Clinical isolates frequently belonged to the O3 and O9 groups whereas these two serotypes were not found in strains from pork. Resistance to multiple antimicrobial agents was rare. When examined by pulsed field gel electrophoresis (PFGE), two strains of fecal origin with an identical pattern of resistance to six antimicrobial agents were shown to be unrelated. Of four clinical isolates with resistances to five antimicrobial agents, two were of the same pulsotype. Retrospectively, it was found that these strains came from two members of the same household and thus represented a mini-outbreak.

Animals↗

The effects of male age on sperm DNA damage in healthy non-smokers.

BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.

Adult↗

Brain atrophy in pure and complicated hereditary spastic paraparesis: a quantitative 3D MRI study.

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p-HSP) and complicated forms (c-HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p-HSP (n = 21) and c-HSP type (n = 12), and 30 age-matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer-independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group (P < 0.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c-HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI-based brain volume quantification, is a biological marker in HSP subtypes.

Adult↗

Molecular cytogenetic characterization of chromosome 9-derived material in a human thyroid cancer cell line.

The incidence of papillary thyroid carcinoma (PTC) increases significantly after exposure of the head and neck region to ionizing radiation, yet we know neither the steps involved in malignant transformation of thyroid epithelium nor the specific carcinogenic mode of action of radiation. Such increased tumor frequency became most evident in children after the 1986 nuclear accident in Chernobyl, Ukraine. In the eight years following the accident, the average incidence of childhood PTCs (chPTC) increased 70-fold in Belarus, 200-fold in Gomel, 10-fold in the Ukraine and 50-fold in Tschnigov, Kiev, Rovno, Shitomyr and Tscherkassy compared to the rate of about 1 tumor incidence per 106 children per year prior to 1986 (Likhtarev et al., 1995; Sobolev et al., 1997; Jacob et al., 1998). To study the etiology of radiation-induced thyroid cancer, we formed an international consortium to investigate chromosomal changes and altered gene expression in cases of post-Chernobyl chPTC. Our approach is based on karyotyping of primary cultures established from chPTC specimens, establishment of cell lines and studies of genotype-phenotype relationships through high resolution chromosome analysis, DNA/cDNA micro-array studies, and mouse xenografts that test for tumorigenicity. Here, we report the application of fluorescence in situ hybridization (FISH)-based techniques for the molecular cytogenetic characterization of a highly tumorigenic chPTC cell line, S48TK, and its subclones. Using chromosome 9 rearrangements as an example, we describe a new approach termed 'BAC-FISH' to rapidly delineate chromosomal breakpoints, an important step towards a better understanding of the formation of translocations and their functional consequences.

Cell Line, Tumor↗

Molecular cytogenetic studies towards the full karyotype analysis of human blastocysts and cytotrophoblasts.

Numerical chromosome aberrations in gametes typically lead to failed fertilization, spontaneous abortion or a chromosomally abnormal fetus. By means of preimplantation genetic diagnosis (PGD), we now can screen human embryos in vitro for aneuploidy before transferring the embryos to the uterus. PGD allows us to select unaffected embryos for transfer and increases the implantation rate in in vitro fertilization programs. Molecular cytogenetic analyses using multi-color fluorescence in situ hybridization (FISH) of blastomeres have become the major tool for preimplantation genetic screening of aneuploidy. However, current FISH technology can test for only a small number of chromosome abnormalities and hitherto failed to increase the pregnancy rates as expected. We are in the process of developing multi-color FISH-based technologies to score all 24 chromosomes in single cells within a three-day time limit, which we believe is vital to the clinical setting. Also, human placental cytotrophoblasts (CTBs) at the fetal-maternal interface acquire aneuploidies as they differentiate to an invasive phenotype. About 20-50% of invasive CTB cells from uncomplicated pregnancies were found to be aneuploid, suggesting that the acquisition of aneuploidy is an important component of normal placentation, perhaps limiting the proliferative and invasive potential of CTBs. Since most invasive CTBs are interphase cells and possess extreme heterogeneity, we applied multi-color FISH and repeated hybridizations to investigate the feasibility of a full karyotype analysis of individual CTBs. In summary, this study demonstrates the strength of Spectral Imaging analysis and repeated hybridizations, which provides a basis for full karyotype analysis of single interphase cells.

Blastocyst↗

Outbreak of human listeriosis associated with tomme cheese in northwest Switzerland, 2005.

During an eight week period in spring 2005, 10 cases of listeriosis were reported in a small area of northwest Switzerland (150,000 inhabitants). Eight cases were in older immunocompromised patients who became ill with bacteraemia (three deaths), and two cases were in pregnant women who had septic abortion. All cases were due to a serotype 1/2a isolate with one of two pulsovars found by PFGE. Patient interviews quickly revealed that a locally made and distributed soft cheese (known as 'tomme') was the food source responsible for the outbreak. Samples of this cheese, and of butter made in the same factory, revealed Listeria monocytogenes sv 1/2a of the same pulsovar in amounts of 1000-10 000 and 10-100 cfu/g, respectively. The prompt suspension of production, the market recall of the product, and a public alert terminated the outbreak. However, two cases of febrile gastroenteritis due to the same strains were reported within 10 days of product recall. The restricted distribution area of the contaminated cheese and the collaboration of local physicians, medical microbiologists and food health services all contributed to a rapid and successful investigation. This small outbreak of listeriosis reinforces the need for a laboratory-based surveillance system with rapid typing, as well as collaboration between physicians and microbiologists.

Adult↗

SKY and FISH analysis of radiation-induced chromosome aberrations: a comparison of whole and partial genome analysis.

For a retrospective dose estimation of human exposure to ionising radiation, a partial genome analysis is routinely used to quantify radiation-induced chromosome aberrations. For this purpose, fluorescence in situ hybridisation (FISH) with whole chromosome painting probes for selected chromosomes is usually applied covering about 20% of the whole genome. Since genome-wide screening techniques like spectral karyotyping (SKY) and multiplex FISH (mFISH) have been developed the detection of radiation-induced aberrations within the whole genome has now become feasible. To determine the correspondence between partial and whole genome analysis of radiation-induced chromosome aberrations, they were measured comprehensively in this study using in vitro irradiated blood samples from three donors. We were able to demonstrate that comparable results can be detected with both approaches. However, complex aberrations might be misinterpreted by partial genome analysis. We therefore conclude that whole genome analysis by SKY is useful especially in the high dose range to correct aberration data for complex exchange aberrations.

Adult↗

Frequency of Norovirus in stool samples from patients with gastrointestinal symptoms in Switzerland.

To determine the frequency of sporadic community-acquired Norovirus (NV) infection in the German-speaking part of Switzerland, an evaluation of gastroenteritis cases seen in physicians' practices between July 2001 and July 2003 was conducted. A total of 699 stool specimens documented to be free of common bacterial pathogens was screened for the presence of NV by RT-PCR. NV was detected in 125 (17.9%) of these specimens. In the seasonal analysis, the highest rate of NV-positive samples (38.3%) was found between January and March 2002. After July 2002, the study was expanded to additionally test for NV in stool samples containing a known bacterial pathogen. Among 132 such specimens, NV was detected in only one. This suggests that NV mixed-infections are playing a marginal role in Switzerland.

Caliciviridae Infections↗

Risk factors for infections with Norovirus gastrointestinal illness in Switzerland.

Viral infections, particularly those caused by noroviruses (NV, genus Norovirus), are the most common cause of community-acquired gastroenteritis in Europe, with respect to both endemic and epidemic occurrence. For the first time, a general practitioner-based case-control study was performed between July 2001 and July 2003 in the German-speaking part of Switzerland in order to identify risk factors for sporadic NV infections. The consumption of different foodstuffs and of bottled mineral water did not show any significant association with the risk of NV gastroenteritis, nor was there any significant effect of individual ABO histo-blood group or household size on the incidence of NV gastroenteritis. The findings are consistent with person-to-person transmission as the most important route of transmission for community-acquired, sporadic NV infection, in that 39% of all patients reported they had had contact with ill persons before their illness. The fact that 33% reported contact with ill persons, mainly within family groups, after their own illness suggested that a substantial proportion of patients were part of family mini-outbreaks.

Adolescent↗

Outbreaks of gastroenteritis due to infections with Norovirus in Switzerland, 2001-2003.

Viral infections, especially those with noroviruses are the most common cause of acute gastroenteritis in Europe. To obtain information about the epidemic situation of noroviruses in Switzerland, an initial study was launched in the German-speaking part of the country to systematically compile Norovirus outbreak information between 2001 and 2003. In total, 73 outbreaks were registered. Most affected were closed settings, e.g. nursing homes (34%) and hospitals (25%). Transmission pathways were identified in 74% of Norovirus outbreaks. In 81% of these cases person-to-person transmission was the primary route of infection and on seven occasions (13%), a foodborne transmission was the possible cause. Furthermore, Norovirus outbreak characteristics of epidemiological importance are highlighted with a discussion of four selected events.

Caliciviridae Infections↗

Midazolam and its metabolites in brain death diagnosis.

OBJECTIVE: There is only limited knowledge on the pharmacokinetics of midazolam and its active metabolites in potential organ donors. Before establishing the diagnosis of brain death, drugs interfering with the neurological assessment have to be washed out. National guidelines advise a waiting time of 12 hours. The aim of our study was to evaluate whether it is sufficient to rely on a calculated waiting time. METHODS: As examples of typical pharmacokinetics of midazolam and its metabolites, we followed the concentration over time in four potential organ donors with immunoassays and high-performance liquid chromatography (HPLC). RESULTS AND CONCLUSIONS: In each of the 4 patients studied, the elimination of midazolam and/or midazolam metabolites was delayed. As long as brain death diagnosis requires that drugs interfering with the clinical assessment must be at levels below the therapeutic range, monitoring of midazolam and metabolites appears mandatory.

Adjuvants, Anesthesia↗

Parallel evaluation of doxorubicin-induced genetic damage in human lymphocytes and sperm using the comet assay and spectral karyotyping.

In recent years, two techniques for detecting genetic damage in the whole genome have gained importance: the alkaline comet assay, to detect DNA damage such as strand breaks and alkali-labile sites, and a multicolour FISH method, spectral karyotyping (SKY), to identify chromosomal aberrations simultaneously in all metaphase chromosomes. In the present study, the induction of DNA damage in human sperm and lymphocytes in vitro has been studied employing an anticancer drug, doxorubicin (DX). An increase in DNA damage was observed with the comet assay as the median per cent head DNA of sperm significantly decreased from 82.07 and 85.14% in the untreated control groups to 63.48 and 72.52% at doses of 0.8 micro M DX. At 1.6 micro M the percentage declined to 60.96% (the corresponding tail moment increased from 4.42 to 12.19). In stimulated lymphocytes, a significant increase was observed in tail moment, from 0.72 and 0.53 in controls to 15.17 and 12.10 at 0.2 micro M DX, continuing at the same level to a final concentration of 1.6 micro M. Structural aberrations found in the parallel SKY study in stimulated lymphocytes at 0.2 micro M DX consisted of 14% chromatid-type and 2% chromosome-type aberrations; none were found in controls. The SKY results correlate very well with the findings of the comet assay in lymphocytes where DNA damage was observed at similar doses. This study is the first reporting use of the comet assay and SKY analysis in parallel after chemical treatment. The potential of the two techniques together is evident, as they represent a set of assays feasible for evaluating damage in human somatic and germ cells after chemical treatment (i) by direct observation of two different end-points, detecting general DNA damage and chromosomal aberrations and (ii) by extrapolation from lymphocytes to sperm, which provides a 'parallelogram' approach in human cells.

Adult↗

Rapid propagation of norovirus gastrointestinal illness through multiple nursing homes following a pilgrimage.

Reported here is an outbreak of gastroenteritis due to Norovirus infection that affected at least 450 persons from nursing homes and similar institutions in Switzerland during and after an organised pilgrimage to Lourdes in France. The outbreak was characteristic of direct person-to-person transmission, with the primary cases occurring in the hospital that harboured some of the pilgrims in Lourdes.

Age Distribution↗

Genotyping of Cryptosporidium spp. isolated from human stool samples in Switzerland.

In a study to estimate the frequency of Cryptosporidium infections in Switzerland, stool samples from patients found to be positive for Cryptosporidium spp. by modified Ziehl-Neelson staining and fluorescence microscopy were used for genotyping experiments. With 9 of 12 samples, DNA extraction and subsequent genotyping was successful. All Cryptosporidium-isolates belonged to the bovine genotype. In one stool sample, two strains of Cryptosporidium were demonstrated, suggesting a mixed infection. In comparison with reference strains from calves, one of the isolates showed a full sequence identity and the other a similarity of 97.5%. The fact that only bovine genotypes were detected suggests, that cryptosporidiosis must primarily be considered as a zoonotic disease in Switzerland. This is in contrast to other countries, where the human genotype of C. parvum was shown to dominate the epidemiological situation. The results of our study are supported by the previous finding, that two of the analysed strains originated from patients who used to consume raw milk or raw cream, a known risk factor for cryptosporidiosis.

Animals↗

Verocytotoxin-producing Escherichia coli in patients with diarrhoea in Switzerland.

The present study was conducted between October 1996 and October 1998 to estimate the frequency of verocytotoxin-producing Escherichia coli among outpatients with diarrhoea in Switzerland. Among 3,041 subjects studied, 16 (0.5%) verocytotoxin-producing Escherichia coli infections were identified. Eleven cases were in infants and children </= 6 years of age. In 15 cases, a verocytotoxin-producing Escherichia coli strain was isolated. These strains belonged to 11 different serotypes, and only two were serogroup O157. In five cases, the infection was probably acquired outside Switzerland. Verocytotoxin-producing Escherichia coli apparently play a minor role in the aetiology of diarrhoeal disease in adult outpatients in Switzerland, but they are important pathogens in preschool children in whom the most severe symptoms are observed.

Adult↗

Induction of aneuploidy in male mouse germ cells detected by the sperm-FISH assay: a review of the present data base.

Multicolour fluorescence in situ hybridization (FISH) with chromosome-specific DNA-probes can be used to assess aneuploidy (disomy) and diploidy in sperm of any species provided the DNA-probes are available. In the present EU research project, DNA-probes for mouse chromosomes 8, X and Y were employed each labelled with different colours. Male mice were treated with the test chemicals and sperm were sampled from the Caudae epididymes 22-24 days later to allow spermatocytes exposed during meiosis to develop into mature sperm. At present, the data base comprises 10 chemicals: acrylamide (AA), carbendazim (CB), colchicine (COL), diazepam (DZ), griseofulvin (GF), omeprazole (OM), taxol (TX), thiobendazole (TB), trichlorfon (TF) and vinblastine (VBL). Of these, COL and TF induced disomic sperm only. DZ and GF induced disomic and diploid sperm, while CB and TB induced diploid sperm only. VBL gave contradictory results in repeated experiments in an inter-laboratory comparison. AA, OM and TX did not induce an increase in disomic or diploid sperm at the doses used. The induction of aneuploidy by DZ was also tested in humans. Sperm samples from patients after attempted suicide and from patients with chronic Valium((R)) abuse were evaluated using human DNA-probes specific for chromosomes 1,16, 21, X and Y. A quantitative comparison between mouse and man indicates that male meiosis in humans is 10-100 times more sensitive than in mice to aneuploidy induction by DZ. The positive response of mice to TF supports the hypothesis by Czeizel et al. [Lancet 341 (1993) 539] that TF may be causally related to the occurrence of congenital abnormality clusters in a Hungarian village.

Acrylamide↗

Subchronic treatment with lithium increases nerve growth factor content in distinct brain regions of adult rats.

There is compelling evidence that withdrawal of neurotrophins can lead to impaired neuronal function and even apoptotic death of neurons. Recent experimental evidence suggests that antidepressant drugs and electroconvulsive treatment might work by enhancing CNS levels of neurotrophins. In addition, Lithium (LI) has been shown to exert robust neuroprotective effects apart from its well known mood-stabilizing effects in humans. In this study we investigated the effects of subchronic (14 days) treatment with various doses of LI on the NGF content of several regions of the adult rat brain. LI treatment, which resulted in prophylactic LI serum concentrations (0.72 +/- 0.08 mMol l(-1)), induced a significant (P < 0.05) increase in NGF concentrations in the frontal cortex (+23.2%), hippocampus (+72%), amygdala (+74%) and limbic forebrain (+46.7%) compared to untreated controls, whereas no effects on NGF concentrations were observed in the striatum, the hypothalamus or the midbrain, even using various LI doses. Moreover, no significant change in NGF concentrations in the frontal cortex was observed after acute (1 day) treatment with LI. Our findings lend support to the notion that an enhancement of NGF production may be specifically involved in the mechanisms of action of antibipolar treatments.

Animals↗

Automated evaluation of frequencies of aneuploid sperm by laser-scanning cytometry (LSC).

BACKGROUND: Laser-scanning cytometry (LSC) allows fast automated scoring of fluorescence signals directly on microscopic slides. Frequencies of spontaneous aneuploidies in murine and human sperm were evaluated by using this new LSC technique. Rapid detection may be of great interest in reproductive toxicology, as certain chemicals act as aneugens during meiosis, increasing the production of aneuploid germ cells. Materials and Methods Selected chromosomes were detected by using fluorescence in situ hybridization (FISH) and fluorochrome-labeled DNA-probes. Sperm chromatin was counterstained with propidium iodide. By scanning across the slide, fluorescence signals within sperm nuclei were detected and counted. RESULTS: In murine sperm, the frequencies of disomies for chromosomes 8 and X were 0.019% and 0.021%, respectively. The automated assessment in human sperm resulted in disomy frequencies of 0.061% and 0.090% for chromosomes 13 and X, respectively. These results were comparable to data obtained from the same samples by manual microscopic scoring and to literature data. CONCLUSIONS: Frequencies of genotypically abnormal sperm were not significantly different between automated and manual scoring. In conclusion, sperm aneuploidy was reliably determined and disomic sperm were successfully relocated by LSC. By virtue of rapid and reliable analyses, LSC has the powerful potential to replace manual microscopic FISH analysis in molecular cytogenetics.

Aneuploidy↗