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Biomedical subjects

M Exner

Publications and source records attributed to M Exner.

At least 55 records · Page 3Linked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

Characterization of the inflammatory infiltrate in autoimmune cholangitis. A morphological and immunhistochemical study.

Autoimmune cholangitis (AIC) is characterised by clinical and/or laboratory features of cholestasis, the presence of antinuclear antibodies and the lack of antimitochondrial antibodies. Histologically, changes largely identical to those found in primary biliary cirrhosis (PBC) are typically found. It is not possible to differentiate between AIC and PBC on conventional morphological grounds, and we therefore wished to find whether there is a difference between these entities in the composition of the inflammatory infiltrate leading to bile duct destruction. In liver biopsies from ten patients with confirmed AIC and ten patients with PBC the inflammatory infiltrate was characterised with antibodies against CD 3, OPD 4 CD 8, GB 7, L 26, CD 56 and CD 57. In AIC, T cells were predominant in the portal inflammatory infiltrate in nine cases. Granzyme B-positive activated cytolytic T lymphocytes were found in the bile duct epithelium in five cases. All these five cases showed inflammatory bile duct destruction. No significant differences between the immunohistochemical findings in AIC and in PBC were found. We suggest that AIC is a subgroup of PBC, antimitochondrial antibody-negative type.

Adult↗
PubMed1998

The influence of chest compressions and external defibrillation on the release of creatine kinase-MB and cardiac troponin T in patients resuscitated from out-of-hospital cardiac arrest.

OBJECTIVES: This study sought to determine the influence of resuscitative procedures, such as chest compressions and external defibrillation, on the release of creatine kinase (CK)-MB and cardiac troponin T (cTnT). METHODS: In 87 patients with out-of-hospital cardiac arrest and successful cardiopulmonary resuscitation (CPR), the initial ECG rhythm, the duration of cardiac arrest and CPR, and the number of defibrillations were assessed on arrival in the hospital. The serum CK-MB and cTnT were measured 12 h after the event. We also assessed whether the patient developed cardiogenic shock within 12 h, and if the patient had acute myocardial infarction (AMI), which was confirmed or eliminated by of typical ECG findings, thallium-201 myocardial scintigraphy, or autopsy within the hospital stay. A backward stepwise linear regression model was applied to assess the association between the markers of myocardial injury (CK-MB and cTnT) and the above clinical variables. RESULTS: CK-MB concentrations were independently associated with the presence of AMI [B 68.5 (SE 28.5, P = 0.018)], the duration of CPR (as a measure of trauma to the chest by means of chest compressions) [B 2.07 (SE 1.01, P = 0.045)] and cardiogenic shock [B 52.3 (SE 23.4, P = 0.03)]. The remaining clinical variables listed were excluded by the model. Cardiac troponin T concentrations were only associated with the presence of AMI [B 4.86 (SE 1.34, P = 0.0005)]. There was a non-significant association between increasing serum cTnT concentrations and the presence of cardiogenic shock [B 2.51 (SE 1.46, P = 0.09)]. The remaining clinical variables were excluded by the model. CONCLUSION: The release of CK-MB appears to be influenced by the duration of resuscitation and the presence of cardiogenic shock. This has to be considered when interpreting serum CK-MB concentrations after CPR. The release of cTnT seems to be only associated with acute myocardial infarction, but not with the duration of chest compressions, or with the number of defibrillations administered.

Aged↗
PubMed1998

Expression of bcl-2, bcl-x, bax and bak in renal parenchyma, oncocytomas and renal cell carcinomas.

Proteins of the bcl-2 family are important regulators of programmed cell death. Alterations in the expression of these proteins may contribute to the progression of cancer. Expression of bcl-2, bcl-x, bax and bak was investigated by immunohistochemistry and Western-blotting of regular and alterated renal parenchyma as well as in 57 renal cell carcinomas. Bcl-2, bcl-x and in part bax were found to be overexpressed in inflammed renal parenchyma, whereas atrophic tubuli predominantly stained for bcl-2 and to a lesser degree for bcl-x and bax. Only little bak expression was detected in alterated tubuli. Moderate to strong expression for bcl-2, bcl-x, bax and bak was found in 24, 38, 2 and 13 of 57 carcinomas, respectively. Bcl-2, bcl-x, bax and bak expression were correlated to tumor type. Chromophilic carcinomas stained stronger for bcl-2, bcl-x and bax, whereas chromophobic carcinomas stained stronger for bcl-x, bax and bak compared to clear cell carcinomas. Expression of bak correlated with that of bcl-x and with an unfavorable histology as indicated by nuclear grading in these tumors. Our findings suggest that expression of bcl-2 and bcl-x may be important for cell survival only in a subset of renal cell carcinomas, and that the anti-apoptotic effect of these proteins appears to be frequently bypassed possibly by other factors impeding programmed cell death.

Adenoma, Oxyphilic↗