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Biomedical subjects

M Burger

Publications and source records attributed to M Burger.

At least 19 recordsLinked to original sources

Prevalence of Mycobacterium avium and Mycobacterium tuberculosis in blood cultures of Brazilian AIDS patients after introduction of highly active retroviral therapy.

The use of highly active antiretroviral therapy (HAART) for the treatment of HIV infection has been associated with a marked reduction in the incidence of most opportunistic infections. From April 2001 to February 2002, 80 blood samples from patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count < 100.0 cell/mL were investigated. Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). The TCD4+ count at the time of M. avium bacteremia ranged from 7 cells/microL (average of 48.5 cell/microL), while in M. tuberculosis bacteremia it ranged from 50.0 cells/microL (average of 80.0 cell/microL). The prevalence of M. avium bacteremia in our study follows the expected decline in opportunistic infections observed after the introduction of HAART; however, mycobacteremia by M. tuberculosis still indicates a high prevalence of tuberculosis infection in AIDS patients.

AIDS-Related Opportunistic Infections↗

[Diabetes mellitus in Germany. Review of the situation according to the 2003 Telephone Health Survey].

Diabetes mellitus is one of the most prevalent endocrine disorders in Germany. Secondary diseases and complications have serious effects on the lives of diabetics. They also represent an important challenge for economic and health policy processes. According to the 2003 Telephone Health Survey, the prevalence of diabetes mellitus among the population aged 18 years and older is 6.1% for women and 5.4% for men. The percentage of diabetics among older population groups is considerably higher (65+: 16%). The need for effective health care for diabetes patients is reflected in frequent medical consultations. At the same time, there are deficiencies in the treatment of diabetes, for example in HbA1c measurement and the examination of diabetics' ocular fundus and feet. Although special training courses for diabetics are well publicized, only one in two diabetics makes use of them. Future surveys will show whether disease management programmes can help bridge the existing health care gaps.

Adolescent↗

[Distribution and patterns of tobacco consumption in Germany].

Tobacco consumption increases the risk of many chronic degenerative diseases and causes considerable social follow-up costs. The ongoing high tobacco consumption in the population, therefore, highlights an area in which health policy action is urgently required. According to the Telephone Health Survey 2003, about 37% of men aged 18 years and older and 28% of women of the same age are smokers. Almost half of the male daily smokers and a third of the female daily smokers consume 20 or more cigarettes a day, thus exposing themselves to a serious health risk. Among persons of socially disadvantaged groups, smoking prevalence is particularly high; they are also more likely to be heavy smokers and less likely to stop smoking. In the last 20 years, tobacco consumption has only declined slightly among men, while it has increased among women. These results underline the necessity for comprehensive tobacco prevention and tobacco control, and this means not only general measures but also initiatives focusing on specific target groups.

Adolescent↗

Methylation discriminators in NSCLC identified by a microarray based approach.

Aberrant DNA methylation is a frequent phenomenon in non-small cell lung cancers. We have used a microarray approach to assess the methylation status of 245 CpG positions in 59 candidate genes in 26 squamous cell carcinomas, and 22 adenocarcinomas as well as 26 normal adjacent lung tissue samples from smokers to identify genes that show a distinct methylation status difference between the two different tumour type tissues and normal adjacent tissue. Tumour tissue samples were grouped together and compared to the normal tissue sample group. A multivariate test was performed, taking into account all CpG positions that were analyzed for a particular gene, to calculate p-values for each gene based on the observed methylation difference between the two groups, p-values obtained were corrected for multiple testing. The highest degree of differential DNA methylation in squamous cell carcinoma compared to normal was observed in ARHI, MGMT, GP1bbeta, RARbeta and TMEFF2 genes, while TMEFF2, MGMT and CDKNIC genes differentiated between adenocarcinomas and normal tissue. It is of note that some of the genes for which differential methylation status was observed, have not been previously described in lung cancer. Our results provide compelling evidence that different histological types of lung cancer may be distinguished from normal tissue based on methylation profiles of specific genes.

Adenocarcinoma↗

Efficient method for mycobacterial DNA extraction in blood cultures aids rapid PCR identification of Mycobacterium tuberculosis and Mycobacterium avium.

The study presented here evaluated the utility of several methods of extracting mycobacterial nucleic acids from positive blood culture samples and examined the effect of each method on the performance of an in-house PCR used directly in the peripheral blood of 80 patients with AIDS to identify Mycobacterium spp. The modified Boom method for extracting DNA from blood cultures proved to be the most efficient, with subsequent PCR analysis yielding 100% positivity (7 samples positive for M. avium and 5 for M. tuberculosis). Only three of 12 patients with a positive blood culture had a PCR result positive for M. avium in peripheral blood. The identification of mycobacteria by PCR in blood culture took about 3 days, reducing the time to diagnosis by several weeks. These results demonstrate that PCR is a sensitive and quick method for identifying mycobacteria, especially when a good DNA extraction method is applied.

Acquired Immunodeficiency Syndrome↗

[What do you eat? Food frequency questionnaire for children and adolescents].

In the German Health Survey for Children and Adolescents (KiGGS), which started in May 2003, about 18,000 representatively chosen children and adolescents will be physically examined and interviewed about their health during a period of 3 years. Since nutrition is a main determinant of health, several aspects such as breastfeeding by the mother, dietary behavior, and eating disorders will be determined. In addition to some specific nutrition questions in the general health questionnaire, consumption frequency and portion sizes of the main food groups will be assessed with a newly developed questionnaire. This questionnaire is presented and its advantages and disadvantages are discussed.

Adolescent↗

Alcohol consumption and its relation to cardiovascular risk factors in Germany.

OBJECTIVE: To analyse the association of alcohol consumption and blood lipids, haemostatic factors, and homocysteine in German adults by gender and age groups. DESIGN: Cross-sectional population-based survey. SETTING: Data from the German National Health Interview and Examination Survey 1998, representative for age, gender, community size, and federal state. SUBJECTS: From a sample of 7124 Germans between 18 and 79 y old, 2420 women and 2365 men were selected. Only individuals who were not currently receiving medical treatment or did not have disorders related to cardiovascular disease were selected for this study. RESULTS: Using analyses of variance, mean blood levels of total cholesterol, HDL cholesterol, HDL/total cholesterol ratio, total glycerides, fibrinogen, antithrombin III, and homocysteine adjusted for age, socioeconomic status, East/West Germany residence, body mass index, tobacco use, sports activity, and coffee consumption, if appropriate are presented by alcohol consumption groups (0, >0-10, >10-20, >20-30 and >30 g/day). The HDL/total cholesterol ratio increased with higher alcohol groups up to 10-20 g/day (+15%) for women and >30 g/day (+18%) for men, showing the strongest rise among men aged 55-79 y. Fibrinogen decreased with higher alcohol groups up to 10-20 g/day for women and 20-30 g/day for men. Among women, homocysteine levels showed a U-shaped curve with a minimum of 8.49 mmol/l at 10-20 g alcohol/day (-8%, reference: nondrinking), whereas an inverse association was observed for men. CONCLUSIONS: Moderate alcohol consumption is associated with favourable levels of several cardiovascular risk factors. The most favourable cardiovascular risk factor profile among women was observed among those drinking 10-20 g alcohol/day. Beneficial effects seem to be more pronounced among older men.

Adult↗

Correlation of virulence, lung pathology, bacterial load and delayed type hypersensitivity responses after infection with different Mycobacterium tuberculosis genotypes in a BALB/c mouse model.

One of the most intriguing aspects of tuberculosis is that the outcome of an infection with M. tuberculosis (TB) is highly variable between individuals. The possibility of differences in virulence between M. tuberculosis strains or genotypes has only recently been studied. There is evidence of multifactorial genetic predisposition in humans that influences the susceptibility to tuberculosis. A better understanding of differences in virulence between M. tuberculosis genotypes could be important with regard to the efforts at TB control and the development of improved antituberculosis vaccines. Survival, lung pathology, bacterial load and delayed type hypersensitivity (DTH) responses of BALB/c mice after intratracheal infection with any of 19 different M. tuberculosis complex strains of 11 major genotype families were studied. The results indicate that among genetically different M. tuberculosis strains a very broad response was present with respect to virulence, pathology, bacterial load and DTH. 'Low'-responders were the H37Rv, Canetti, Beijing-1 strains, while Beijing-2,3, Africa-2 and Somalia-2 strains were 'high'-responders. A severe pathological response correlates with a high mortality and a high CFU counts in lungs, but poorly with the degree of the DTH response.

Animals↗

A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes.

In the last decade, an unprecedented genetic diversity has been disclosed among Mycobacterium tuberculosis strains found worldwide. However, well-conserved genotypes seem to prevail in areas with high incidence of tuberculosis. As this may be related to selective advantages, such as advanced mechanisms to circumvent [M. bovis Bacille Calmette-Guerin (BCG)-induced] host defence mechanisms, we investigated the influence of strain diversity on the course of experimental disease. Twelve M. tuberculosis strains, representing four major genotype families found worldwide today, and the laboratory strain H37Rv were each used to infect BALB/c mice by direct intratracheal injection. Compared with H37Rv, infections with Beijng strains were characterized by extensive pneumonia, early but ephemeral tumour necrosis factor-alpha (TNF-alpha) and inducible isoform of nitric oxide synthetase (iNOS) expression, and significantly higher earlier mortality. Conversely, Canetti strains induced limited pneumonia, sustained TNF-alpha and iNOS expression in lungs, and almost 100% survival. Strains of the Somali and the Haarlem genotype families displayed less homogeneous, intermediate rates of survival. Previous BCG vaccination protected less effectively against infection with Beijing strains than against the H37Rv strain. In conclusion, genetically different M. tuberculosis strains evoked markedly different immunopathological events. Bacteria with the Beijing genotype, highly prevalent in Asia and the former USSR, elicited a non-protective immune response in mice and were the most virulent. Future immunological research, particularly on candidate vaccines, should include a broad spectrum of M. tuberculosis genotypes rather than a few laboratory strains.

Animals↗

Long-term follow up of childhood tuberculous meningitis.

The purpose of the present study was to determine the long-term outcome of 76 children (40 females and 36 males) diagnosed and treated with modern antituberculosis drugs. The median age of the children on admission was 29.5 months and on follow-up 9 years. Antituberculosis therapy consisted of daily isoniazid (20 mg/kg), rifampicin (20 mg/kg), ethionamide (20 mg/kg), and pyrazinamide (40 mg/kg) for 6 months. Twenty-three children received daily prednisone (2-4 mg/kg) for the first month of treatment. Raised intracranial pressure was actively monitored and treated. Patients with non-communicating hydrocephalus received ventriculo-peritoneal shunts shortly after admission while communicating hydrocephalus was treated with oral acetazolamide (100 mg/kg/day) and furosemide (1 mg/kg/day) in 3-4 divided doses. Communicating hydrocephalus that did not respond to this regimen within the first month of treatment also underwent ventriculo-peritoneal shunting. Only 20% of children were functionally completely normal at follow-up. Main areas of functional deficit were cognitive impairment (80%), poor scholastic progress (43%), and emotional disturbance (40%). Twenty-five per cent of children had evidence of motor impairment, but all could walk and only 5 of 76 children (6% of total) were unable to run. One child was blind but no child had sensori-neural deafness. It was concluded that these disabilities in children from mainly deprived socioeconomic backgrounds have serious implications for their future social, academic, and career prospects. A high index of suspicion of TBM in high tuberculosis incidence communities will help prevent the morbidity documented in this study.

Acetazolamide↗

[The Child and Adolescent Health Survey: collection of health behavior data from parents and children].

The first German Health Survey for Children and Adolescents will start in 2003. During three years, a representative sample of children and adolescents between 0 and 18 years of age shall be examined and will, together with their parents, be interviewed on health-relevant issues. With this survey, health information on about 18,000 children will be gathered. The health behaviour of the parents as far as their children's health is concerned, as well as the personal health behaviour during adolescence will be assessed, since this will be highly relevant for future health. Questions on nutrition behaviour, eating disorders, alcohol consumption, smoking as well as leisure-time behaviour, with special emphasis on physical activity, will be asked. These questions were tested for feasibility in a one-year pilot study. With this survey, the occurrence of certain unhealthy behaviour characteristics may be documented and risk groups may be identified. This may help to conceptualize prevention measures.

Adolescent↗

The Escherichia coli orthologue of the Salmonella ushB gene (ushB(c)) produces neither UDP-sugar hydrolase activity nor detectable protein, but has an identical sequence to that of Escherichia coli cdh.

Salmonella ushB, which encodes a membrane-bound UDP-sugar hydrolase, has an Escherichia coli orthologue (ushB(c)) which does not detectably produce this activity. In this report, we show that ushB(c) does not produce any detectable protein either, despite being transcribed normally. Remarkably, ushB(c) is shown to have 100% sequence identity with E. coli cdh, previously characterised as encoding an active CDP-diglyceride hydrolase, an apparent contradiction with implications regarding enzyme evolution. We suggest that a useful gene designation is cdh (ushB(c)) rather than either ushB(c) or cdh, alone.

Blotting, Southern↗

IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways.

Stimulation of microvascular endothelial cells with interleukin (IL)-8 leads to cytoskeletal reorganization, which is mediated by combined activation of the CXCR1 and the CXCR2. In the early phase actin stress fibers appear, followed by cortical actin accumulation and cell retraction leading to gap formation between cells. The early response (between 1 and 5 min) is inhibited by an antibody that blocks the CXCR1. The later phase (from about 5 to 60 min), which is associated with cell retraction, is prevented by anti-CXCR2 antibody. Furthermore, anti-CXCR2, but not anti-CXCR1, antibody blocked IL-8-mediated haptotaxis of endothelial cells on collagen. The later phase of the IL-8-mediated actin response is inhibited by pertussis toxin, indicating that the CXCR2 couples to G(i). In contrast, the early phase is blocked by C3 botulinum toxin, which inactivates Rho, and by Y-27632, which inhibits Rho kinase, but not by pertussis toxin. Furthermore, the early CXCR1-mediated formation of stress fibers was prevented by dominant negative Rho. Dominant negative Rac on the other hand initially translocated to actin-rich filopodia after stimulation with IL-8 and later prevented cell retraction by blocking the CXCR2-mediated cytoskeletal response. These results indicate that IL-8 activates both the CXCR1 and the CXCR2 on microvascular endothelial cells, using different signal transduction cascades. The retraction of endothelial cells due to activation of the CXCR2 may contribute to the increased vascular permeability observed in acute inflammation and during the angiogenic response.

ADP Ribose Transferases↗

Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1.

A subset of blood cells from patients with B-cell chronic lymphocytic leukemia (CLL) spontaneously differentiates in vitro into large, round, or fibroblast-like adherent cells that display stromal cell markers, namely vimentin and STRO-1. These cells also express stromal cell-derived factor-1 (SDF-1), a CXC chemokine that ordinarily is secreted by marrow stromal cells. Leukemia B cells attach to these blood-derived adherent cells, down-modulate their receptors for SDF-1 (CXCR4), and are protected from undergoing spontaneous apoptosis in vitro. Neutralizing antibodies to SDF-1 inhibit this effect. Moreover, the rapid deterioration in the survival of CLL B cells, when separated from such cells, is mitigated by exogenous SDF-1. This chemokine also results in the rapid down-modulation of CXCR4 and activation of p44/42 mitogen-activated protein-kinase (ERK 1/2) by CLL B cells in vitro. It is concluded that the blood of patients with CLL contains cells that can differentiate into adherent nurse-like cells that protect leukemia cells from undergoing spontaneous apoptosis through an SDF-1-dependent mechanism. In addition to its recently recognized role in CLL B-cell migration, SDF-1-mediated CLL B-cell activation has to be considered a new mechanism involved in the microenvironmental regulation of CLL B-cell survival. (Blood. 2000;96:2655-2663)

Apoptosis↗

A low-molecular-weight cytosolic inhibitor of the specific testosterone binding in bovine seminal vesicles.

Bovine seminal vesicle cytosol contains a low-molecular-weight and thermostable substance which specifically inhibits the binding of testosterone to its cognate receptor. The mass and the ether phospholipid structure of the inhibitor were elucidated by mass spectrometry. Saturation and binding experiments indicate that the inhibitor acts in a dose-dependent and competitive manner, altering the apparent dissociation constant (K(D)) while maintaining the number of androgen-binding sites (B(max)). Its possible role in the regulation of androgen binding activity is discussed.

Animals↗

The effect of sildenafil on human sperm motion and function from normal and infertile men.

The aim of this report was to study the effect of sildenafil, a specific type-5 phosphodiesterase inhibitor, on human sperm motility, viability, membrane integrity and sperm penetration assay. Spermatozoa were obtained from normal donors (n = 6) and infertile men (n = 6) were washed using a single Percoll (80%) gradient, suspended in Ham's F-10 medium, and incubated with various doses of sildenafil (125, 250 and 750 ng/ml); pentoxifylline (3 mM) was used as a positive control, and Ham's F-10 was used as a reagent control. Sperm motility, grade, viability, membrane integrity (by hypo-osmotic swelling test), and motion evaluation were carried out at various time intervals. Hamster ova sperm penetration assay (SPA) was used to evaluate overall sperm function. Sildenafil did not affect sperm motility, viability or membrane integrity under these conditions as compared to our Ham's control (P> 0.05). Incubation with pentoxifylline significantly enhanced sperm motility (P < 0.05) and viability without affecting membrane integrity (P < 0.05). Sperm incubated with sildenafil and pentoxifylline from both normal donors and infertile patients demonstrated no significant change in sperm penetration assay from respective controls. In conclusion, sildenafil, at the doses evaluated, did not significantly alter the motility, viability, membrane integrity or sperm penetration characteristics of human spermatozoa from normal donors and infertile patients.

Animals↗