[100 years public health exemplified by the contributions of August Gartner to the modern drinking water supply].
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Germany↗
Biomedical subjects
M Exner
Publications and source records attributed to M Exner.
The "typical" immunophenotype of acute promyelocytic leukemia (APL-M3): does it prove true for the M3-variant?
The immunophenotypes of 12 acute promyelocytic leukemias (APL-M3; eight hypergranular, four microgranular) with documented PML-RAR-alpha fusion gene are presented. Bone marrow mononuclear cells were immunophenotyped using a panel of 20 monoclonal antibodies. The hypergranular APLs exhibited a mature myeloid phenotype as it has been described to be typical for M3. No lineage infidelity was detectable in classic M3 cases. In contrast, among the four cases of M3 variant, all leukemias showed marked expression of CD34 and two of four cases expressed the HLA-DR antigen. The CD2 antigen was expressed in three of four cases. Furthermore, one case showed expression of the CD56 antigen, and one case was positive for the blood group H antigen. The data suggest that microgranular APL is a heterogeneous entity with regard to the immunologic phenotype.
Adult↗
Workplace-related complaints due to exposure to contaminated humidifier water and the VDI guideline 6022
We describe a case report of one patient with hypersensitivity pneumonitis (humidifier lung) due to exposure to contaminated humidifier water and another four patients with related complaints. The setting was a building with photographic laboratories and corresponding office rooms that were supported with air by a humidification, ventilation, and air conditioning (HVAC) system. In the humidifier water, we found different fungi, particularly species of the genus Verticillium, as well as gramnegative bacteria, but no Legionella species. Colony counts were done according to the German Drinking Water Regulations and the VDI Guideline 6022 at 20 degrees C and 36 degrees C; the results exceeded the recommended level of 103 cfu/ml. The hygienic role of the isolated microorganisms and their products (e.g., antigens, endotoxins) is discussed. The case report emphasizes the importance of careful maintenance and control of HVAC systems. The new VDI guideline 6022 (issue July 1998) gives detailed information on this subject and pays special attention to qualifications and training of the HVAC operations staff.
Journal Article↗
The salicylate metabolite gentisic acid, but not the parent drug, inhibits glucose autoxidation-mediated atherogenic modification of low density lipoprotein.
Oxidation of low density lipoprotein (LDL) by glucose-derived radicals may play a role in the aetiology of atherosclerosis in diabetes. Salicylate was shown to scavenge certain radicals. In the present study, aspirin, salicylate and its metabolites 2,5- and 2, 3-dihydroxybenzoic acid (DHBA) were tested for their ability to impair LDL oxidation by glucose. Only the DHBA derivatives, when present during LDL modification, inhibited LDL oxidation and the increase in endothelial tissue factor synthesis induced by glucose oxidised LDL. The LDL glycation reaction was not affected by DHBA. The antioxidative action of DHBA may be attributed to free radical scavenging and/or chelation of transition metal ions catalysing glucose autoxidation.
Arteriosclerosis↗
Role of immunological lymphocyte subset typing as a screening method for lymphoid malignancies in daily routine practice.
BACKGROUND: The major diagnostic role of peripheral lymphocyte subset typing is to distinguish between malignant and reactive conditions. METHODS: The present study evaluates the screening efficacy of flow cytometric lymphocyte subset typing for the presence of a lymphoid malignancy. Four hundred samples were analyzed with a combination of anti-T-, B-, and natural killer (NK)-cell monoclonal antibodies. RESULTS: Two hundred and twenty (55%) samples showed a normal distribution of lymphocyte subsets, 73 (18%) samples exhibited unspecific alterations of lymphocyte subsets, 19 (5%) samples exhibited a reactive phenotype typical of Epstein-Barr virus/cytomegalovirus (EBV/CMV) infection, and 88 (22%) samples expressed a phenotype suggestive of lymphoma. The most predictive independent factor of a lymphoma-specific phenotype was the absolute lymphocyte count (P = 0.0001, odds ratio 73.225). Seventy-eight percent of samples containing >/=4 x 10(9)/l lymphocytes and 2% of samples with lymphocyte counts <4 x 10(9)/l exhibited a lymphoma-specific phenotype. The specificity of the referring clinical comment was the second best predictor of a lymphoma-specific typing outcome (P = 0.0001, odds ratio 19.589). The independent predictive values of lymphocyte morphology and of relative lymphocyte counts were of borderline significance. CONCLUSIONS: The use of flow cytometric lymphocyte subset typing as a diagnostic screening method for lymphoma should be restricted to cases of unexplained elevation of absolute lymphocyte counts with or without morphological atypias and to cases with definite clinical symptoms of lymphoma.
Cytomegalovirus Infections↗
Role of humoral immune reactions as target for antirejection therapy in recipients of a spousal-donor kidney graft.
Excellent graft outcome has been reported for spousal-donor kidney transplantation. In husband-to-wife transplantation, however, a tendency toward inferior graft survival has been described for recipients who were previously pregnant. In our series of spousal-kidney transplantations (nine transplantations; three female recipients), actual graft survival is 100% (median observation time, 339 days). Five patients experienced early allograft rejection. In four transplant recipients, rejection was easily reversible by conventional antirejection therapy. In a multiparous recipient, however, mild interstitial allograft rejection associated with early graft dysfunction was resistant to anticellular treatment (antilymphocyte antibody, tacrolimus rescue therapy). The particular finding of polymorphonuclear neutrophils in peritubular capillaries and the finding of diffuse capillary deposits of the complement split product, C4d, in a posttransplantation biopsy specimen suggested a role of antibody-mediated graft injury. Retrospective flow cytometry cross-matching showed the presence of preformed immunoglobulin G (IgG) antibodies to HLA class I antigens that were not detectable by pretransplantation lymphocytotoxic cross-match testing or screening for panel reactive antibodies. After transplantation, however, complement-fixing antibodies, also presumably triggered by reexposure to spousal-donor HLA antigens, could be detected in the patient's serum. These findings suggested antibody-mediated allograft rejection and led to the initiation of immunoadsorption therapy (14 sessions) with staphylococcal protein A. Selective removal of recipient IgG resulted in complete reversal of graft dysfunction. Our findings suggest that in husband-to-wife transplantation, donor-specific antibodies, presumably triggered by previous pregnancies, might occasionally induce sustained allograft dysfunction. Thus, in this particular setting, a detailed immunologic and histopathologic work-up regarding antibody-mediated allograft dysfunction is warranted because immunoadsorption may be a highly effective treatment modality.
Antibody Formation↗
Neutrophil beta(2)-microglobulin and lactoferrin content in renal failure patients.
Multiple dysfunctions of polymorphonuclear leukocytes (PMNLs) contribute significantly to the increased morbidity and mortality among patients with end-stage renal disease. In the present study, we measured the PMNL content of beta(2)-microglobulin (beta(2)m) and lactoferrin in different states of renal insufficiency and after kidney transplantation. PMNLs were lysed ultrasonically and, after centrifugation, both proteins were assayed in the supernatant by enzyme-linked immunosorbent assay technique. Despite marked differences in plasma beta(2)m levels, no significant difference in PMNL content of beta(2)m and lactoferrin could be shown among the groups analyzed. There was also no correlation between plasma beta(2)m level and PMNL beta(2)m content. In control subjects, as well as in renal allograft recipients with a well-functioning graft, PMNL beta(2)m level correlated positively with PMNL lactoferrin level (pooled data, r = 0.55; P < 0.001; n = 55). Both proteins are considered to colocalize in peroxidase-negative PMNL granules. However, no correlation was found in the azotemic and uremic patient groups. Standard immunofluorescence staining of control PMNLs showed a cytoplasmic granular distribution of both granule proteins. However, in PMNLs of uremic patients, lactoferrin shifted to a perinuclear localization. PMNLs obtained from uremic individuals failed to elicit an increase in lactoferrin release after stimulation with the chemotactic peptide f-Met-Leu-Phe compared with PMNLs obtained from healthy volunteers. These data indicate abnormalities in uremic patients of PMNL granule lactoferrin content and release that are reversible after successful renal transplantation.
Adult↗
Kinetic and mechanistic studies of the peroxynitrite-mediated oxidation of oxymyoglobin and oxyhemoglobin.
Kinetic studies of the peroxynitrite-mediated oxidations of oxymyoglobin (MbFeO(2)) and oxyhemoglobin (HbFeO(2)) showed that the mechanisms of these reactions are more complex than what had previously been reported; both reactions proceed in two steps. For myoglobin, we found that the small amount of deoxymyoglobin (MbFe(II)) which is in equilibrium with MbFeO(2) is first oxidized by peroxynitrous acid to ferryl myoglobin (MbFe(IV)=O). Then, in the second step, MbFe(IV)=O is reduced by peroxynitrous acid to metmyoglobin (metMb). The second-order rate constant values obtained at pH 7.3 and 20 degrees C for the two steps are (5.4 +/- 0.2) x 10(4) and (2.2 +/- 0.1) x 10(4) M(-)(1) s(-)(1), respectively. Analogous studies with hemoglobin suggest that its reaction with peroxynitrite follows the same mechanism. In this case, the second-order rate constant values measured at pH 7.0 and 20 degrees C for the two steps are (8.8 +/- 0.4) x 10(4) and (9.4 +/- 0.7) x 10(4) M(-)(1) s(-)(1), respectively. A possible mechanism in the absence as well as in the presence of CO(2) and the relevance of these reactions in vivo are discussed.
Carbon Dioxide↗
The 4G/4G genotype at nucleotide position -675 in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene is less frequent in young patients with minor stroke than in controls.
Genetic risk factors play an important role in the aetiology of vascular diseases. The insertion/deletion polymorphism (4G/5G) in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene has been associated with an increased risk of myocardial infarction. We investigated 136 patients with minor stroke (MS) and transient ischaemic attack (TIA) and found a prevalence of 0.32 for the 4G/4G genotype in patients compared with 0.42 in 115 age-matched healthy controls. The 4G/4G genotype was significantly less frequent among 61 patients symptomatic before the age of 60 years (prevalence 0.20) than in 75 patients symptomatic after 60 years of age (prevalence 0.42; odds ratio). Our results indicate that the 4G/4G genotype is not a risk factor for MS or TIA and may even be protective in young patients.
Case-Control Studies↗
The association between C-reactive protein on admission and mortality in patients with acute myocardial infarction.
OBJECTIVE: In patients presenting with acute myocardial infarction the pathophysiologic and prognostic value of serum C-reactive protein is not well defined. This study assessed the association between serum C-reactive protein levels on admission and mortality in patients admitted because of acute myocardial infarction. DESIGN: Retrospective cohort study. SETTING: Tertiary care centre. PATIENTS: A total of 729 patients with acute myocardial infarction admitted within a period of 3 years. MAIN OUTCOME MEASURES: C-reactive protein levels on admission, cardiovascular risk factors and survival within the observational period. RESULTS: Within the 3-year observational period, 118 patients died of a cardiovascular cause. With increasing serum C-reactive protein levels (<0.5, 0.5 to <2, 2 to <5, 5-10 and >10 mg dL-1) mortality also increased (14%, 19%, 20%, 39% and 28%, respectively). When controlling for the confounding effect of age, thrombolytic treatment, the time interval between onset of pain and admission, smoking, diabetes mellitus, hypercholesterolemia, hypertension, and elevated creatine kinase on admission in a multivariate Cox regression model, there was only a weak and nonsignificant association between increased serum C-reactive protein and the risk of death. CONCLUSIONS: Patients with elevated concentrations of serum C-reactive protein admitted to the hospital because of acute myocardial infarction are at an increased risk of dying. This association is however, largely explained by other baseline variables, in particular by an estimate of the duration of myocardial ischaemia. If C-reactive protein measured by means of an ultra-sensitive assay is more suitable for risk stratification of unselected patients with acute myocardial infarction, needs further study.
Aged↗
GIS-supported investigation of a nosocomial Salmonella outbreak.
Within an outbreak at a university hospital 102 persons (44 patients, 26 nursery school children and one relative as well as 31 employees) have been diagnosed to be infected by Salmonella enteritidis. Ninety-nine persons complied with the "primary case"-definition. The source of infection could not be detected in retrospect by hygienic-microbiological methods due to missing food samples. But GIS (Geographical Information System)-supported epidemiological investigation and analysis of food production showed that most likely vanilla pudding had been the vehicle of infection. Contamination of the pudding could be put down to the fact that its production took place in direct spatial and temporal association with the preparation of turkey. Probably further infections caused by this primary source were avoided by immediate measures. The making out of an HACCP-concept as well as structural and technical short-term redevelopment measures proved to be decisive factors to decrease the risk of further infections. From these experiences, some recommendations could be derived for the investigation of food-borne outbreaks in hospitals.
Adult↗
[Perception of environmental health in public opinion. Medical history, political, institutional aspects and future challenges].
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Environmental Health↗
Drinking water hygiene in the 21st. century--what can be done?
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Communicable Disease Control↗
Salicylate inhibits LDL oxidation initiated by superoxide/nitric oxide radicals.
Simultaneously produced superoxide/nitric oxide radicals (O2*-/NO*) could form peroxynitrite (OONO-) which has been found to cause atherogenic, i.e. oxidative modification of LDL. Aromatic hydroxylation and nitration of the aspirin metabolite salicylate by OONO- has been reported. Therefore we tested if salicylate may be able to protect LDL from oxidation by O2*-/NO* by scavenging the OONO reactive decomposition products. When LDL was exposed to simultaneously produced O2*-/NO* using the sydnonimine SIN-1, salicylate exerted an inhibitory effect on LDL oxidation as measured by TBARS and lipid hydroperoxide formation and alteration in electrophoretic mobility of LDL. The cytotoxic effect of SIN-1 pre-oxidised LDL to endothelial cells was also diminished when salicylate was present during SIN-1 treatment of LDL. Spectrophotometric analysis revealed that salicylate was converted to dihydroxybenzoic acid (DHBA) derivatives in the presence of SIN-1. 2,3- and 2,5-DHBA were even more effective to protect LDL from oxidation by O2*-/NO*. Because O2*-/NO* can occur in vivo, the results may indicate that salicylate could act as an efficacious inhibitor of O2*-/NO* initiated atherogenic LDL modification, thus further supporting the rationale of aspirin medication regarding cardiovascular diseases.
Free Radical Scavengers↗
Glomerular overproduction of oxygen radicals in Mpv17 gene-inactivated mice causes podocyte foot process flattening and proteinuria: A model of steroid-resistant nephrosis sensitive to radical scavenger therapy.
Focal segmental glomerulosclerosis is a steroid-resistant glomerular disease characterized by foot process flattening and heavy proteinuria. A similar disease was found to occur spontaneously in mice in which the Mpv17 gene was inactivated by retroviral insertion (Mpv17-/- mice). Here evidence is provided that glomerular damage in this murine model is due to overproduction of oxygen radicals and accumulation of lipid peroxidation adducts that were found in isolated glomeruli of Mpv17-/- mice. The development of glomerular disease in Mpv17-/- mice was inhibited by scavengers of oxygen radicals (dithiomethylurea) and lipid peroxidation (probucol), but not by steroid treatment. Although the glomerular polyanion was greatly reduced in proteinuric Mpv17-/- mice, it was preserved by antioxidative therapy. These results indicate that the glomerular disease in Mpv17-/- mice qualifies as a model of steroid-resistant focal segmental glomerulosclerosis and that experimental therapies with scavengers of oxygen radicals and lipid peroxidation efficiently ameliorate glomerular damage.
Aging↗
Exposure of submarine personnel to house dust mite allergens.
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Allergens↗
Sick building syndrome in an office building formerly used by a pharmaceutical company: a case study.
In the past two decades, a group of health problems related to the indoor environment--generally termed sick building syndrome (SBS)--has emerged. We present an investigation of SBS in employees of a ministry working in a naturally ventilated office building that formerly had been used by a pharmaceutical company. A preceding environmental monitoring had failed to identify the cause(s) for the complaints. We conducted a questionnaire-based investigation and categorized the building sections and rooms according to their renovation status and their former use, respectively. The highest level of complaints was found among the employees working in rooms that in the past had been used for the production or storage of various pharmaceutical products suggesting that pharmaceutical odors may be a risk factor for SBS. Clinical laboratory tests did not show any unusual results. We conclude that the former use of a building for production and storage of pharmaceutical products should be considered as a possible risk factor for complaints about indoor air quality, e.g., when advising about or planning for renovations of buildings formerly used for production, handling, or storing of chemicals.
Adult↗