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Biomedical subjects

M Exner

Publications and source records attributed to M Exner.

At least 19 recordsLinked to original sources
PubMed2002

The higher disinfectant resistance of nosocomial isolates of Klebsiella oxytoca: how reliable are indicator organisms in disinfectant testing?

The Children's Clinic in Giessen, Germany recently reported several severe infections with Klebsiella oxytoca resulting in deaths of two neonates. The putative source of the infections was a contaminated infusion solution. The resistance to disinfectant of the K. oxytoca isolates was investigated in three independent laboratories and was indeed found to be significantly increased. Comparative tests with standard strains of K. oxytoca and other recommended bacterial surrogates showed the disinfection procedures used were fully effective. The higher resistance of the nosocomial isolates may have developed due to improper handling and storage of the cleaning utensils. This report describes the events and draws conclusions concerning the use of disinfectants, the treatment of cleaning utensils, the reliability of procedures for testing disinfectants, and suggests additional measures.

Adolescent↗
PubMed2002

Microbial load of drinking water reservoir tributaries during extreme rainfall and runoff.

Hygienic and microbiological examinations of watercourses are usually not carried out during heavy rainfall and runoff events. After rainfall or snowmelt, there are often massive increases in turbidity in flooding creeks in mountain ranges, which are frequently interpreted as an indication of microbial contamination. The aim of this study was to quantify the microbial loads of watercourses during such runoff events and to compare these loads with loads occurring during regular conditions. In a 14-month monitoring period we investigated the microbial loads of three tributaries of different drinking water reservoirs. A total of 99 water samples were taken under different runoff conditions and analyzed to determine physical, chemical, bacterial, and parasitic parameters. Thirty-two water samples were considered event samples during nine measuring series. The criteria for events, based on duration and intensity of precipitation, water depth gauge measurements, and dynamics, had been fixed before the investigation for each creek individually. Of the physical and chemical parameters examined, only the turbidity, pH, and nitrate values differed clearly from the values obtained for regular samples. Most of the bacteriological parameters investigated (colony, Escherichia coli, coliform, fecal streptococcal, and Clostridium perfringens counts) increased considerably during extreme runoff events. If relevant sources of parasitic contamination occurred in catchment areas, the concentrations of Giardia and Cryptosporidium rose significantly during events. The results show that substantial shares of the total microbial loads in watercourses and in drinking water reservoirs result from rainfall and extreme runoff events. Consequently, regular samples are considered inadequate for representing the microbial contamination of watercourse systems. The procedures for raw water surveillance in the context of multiple-barrier protection and risk assessment ought to include sampling during extreme runoff situations.

Rain↗
PubMed2001

Kinetic and mechanistic studies of the NO*-mediated oxidation of oxymyoglobin and oxyhemoglobin.

The second-order rate constants for the reactions between nitrogen monoxide and oxymyoglobin or oxyhemoglobin, determined by stopped-flow spectroscopy, increase with increasing pH. At pH 7.0 the rates are (43.6 +/- 0.5) x 10(6) M(-1) x s(-1) for oxymyoglobin and (89 +/- 3) x 10(6) M(-1) x s(-1) for oxyhemoglobin (per heme), whereas at pH 9.5 they are (97 +/- 3) x 10(6) M(-1) x s(-1) and (144 +/- 3) x 10(6) M(-1) x s(-1), respectively. The rate constants for the reaction between oxyhemoglobin and NO* depend neither on the association grade of the protein (dimer/tetramer) nor on the concentration of the phosphate buffer (100-1 mM). The nitrogen monoxide-mediated oxidations of oxymyoglobin and oxyhemoglobin proceed via intermediate peroxynitrito complexes which were characterized by rapid scan UV/vis spectroscopy. The two complexes MbFe(III)OONO and HbFe(III)OONO display very similar spectra with absorption maxima around 500 and 635 nm. These species can be observed at alkaline pH but rapidly decay to the met-form of the proteins under neutral or acidic conditions. The rate of decay of MbFe(III)OONO increases with decreasing pH and is significantly larger than those of the analogous complexes of the two subunits of hemoglobin. No free peroxynitrite is formed during these reactions, and nitrate is formed quantitatively, at both pH 7.0 and 9.0. This result indicates that, as confirmed from protein analysis after reacting the proteins with NO* for 10 times, when peroxynitrite is coordinated to the heme of myoglobin or hemoglobin it rapidly isomerizes to nitrate without nitrating the globins in physiologically significant amounts.

Animals↗
PubMed2001

A common C-->T polymorphism at nt 46 in the promoter region of coagulation factor XII is associated with decreased factor XII activity.

Coagulation factor XII (FXII) deficiency is rarely found to be associated with bleeding, but single reports demonstrated thromboembolic events in FXII-deficient patients. Currently, the biological role of FXII is still discussed controversially. It is well known that plasma levels of FXII show great interindividual variability. Recently, it has been demonstrated that a frequently occurring C-->T polymorphism in the FXII promoter region at nucleotide (nt) 46 is associated with lower plasma FXII activity levels in Orientals. In our study, we evaluated the frequency of this polymorphism in a randomly selected sample of newborns and investigated whether this C-->T polymorphism also contributes to the frequently observed moderate FXII deficiency in Europeans. We developed a new mutagenically separated polymerase chain reaction assay (MS PCR), which allows mutation detection without the use of restriction enzymes. Among 100 healthy newborns, we found 64% homozygous carriers of the wildtype FXII 46C allele, 29% were heterozygous for FXII C46T, and 7% homozygous for FXII 46T. Evaluation of plasma FXII activity and genotype in 80 randomly selected and unrelated individuals revealed a highly statistically significant (P<.001) association of the FXII 46T allele with reduced FXII plasma activity. Individuals carrying the homozygous FXII 46C genotype had a mean of 1.17 U/ml (+/-0.31 U/ml), individuals heterozygous for FXII C46T showed a mean of 0.70 U/ml (+/-0.31 U/ml), and subjects homozygous for FXII 46T had only 0.44 U/ml (+/-0.10 U/ml) plasma FXII activity.

Alleles↗
PubMed2001

p-Hydroxyphenylacetaldehyde, the major product of tyrosine oxidation by the activated myeloperoxidase system can act as an antioxidant in LDL.

The oxidative modification of low density lipoprotein (LDL) may play a significant role in atherogenesis. HOCl generated by the myeloperoxidase/H2O2/Cl- system of activated neutrophils may be operative in vivo making LDL atherogenic. Tyrosine has been found to be oxidized by HOCl to p-hydroxyphenylacetaldehyde (p-HA) capable of modifying phospholipid amino groups in LDL. As an amphiphatic phenolic compound, p-HA may have the potential to act as an antioxidant in the lipid phase of LDL. The present results show that (a) tyrosine exerts a protective effect on LDL modification by HOCl, (b) p-HA could act as antioxidant associated with the lipoprotein preventing cell- and transition metal ion-mediated LDL oxidation and (c) p-HA was able to scavenge free radicals.

Acetaldehyde↗
PubMed2001

Semicarbazide-sensitive amine oxidase catalyzes endothelial cell-mediated low density lipoprotein oxidation.

OBJECTIVE: Deamination products of semicarbazide-sensitive amine oxidases (SSAO), i.e. aldehydes, superoxide and ammonia have been shown to initiate vascular damage. SSAOs are copper-enzymes, present in endothelial (EC), smooth muscle cells (SMC) and in blood. Transition metals ions (Cu, Fe) mediate the oxidative (atherogenic) modification of LDL by SMC and EC. The physiological source of the active metal ions is still under debate. We hypothesize that SSAOs may catalyze LDL oxidation by endothelial cells via enzyme-complexed Cu++. METHODS: EC isolated from human umbilical veins and cultured in 35 mm wells in RPMI-1640 medium were used as LDL oxidation system. RESULTS: Diamine oxidase (DAO), a SSAO which activity is elevated in tissues and sera of diabetic patients, catalyzes the oxidation of LDL by EC. In the presence of purified DAO (0.07 to 70 U/l) LDL oxidation was increased up to 10-fold as measured by thiobarbituric acid reactive substance (TBARS) formation as well as apoprotein modification of LDL. Chemical blockage of the SSAO substrate binding site did not inhibit the catalytic effect of DAO on LDL oxidation. Denaturation of the enzyme did not destroy the ability of the preparation to facilitate LDL oxidation by EC. The potential of the enzyme to catalyze LDL oxidation was not suppressed in the presence of serum. However, selective removing of enzyme-copper completely abolished the ability of the enzyme to trigger cell-mediated LDL oxidation. CONCLUSION: DAO, beside generating angiopathic deamination products, has the potential to act as a pathophysiological catalyst of LDL atherogenic modification by vascular cells.

Amine Oxidase (Copper-Containing)↗
PubMed2001

Disinfectant activity against different morphological forms of Helicobacter pylori: first results.

The pathogenic bacterium Helicobacter pylori, which has infected more than one-half of the world's human population, exists in two morphological forms; the viable helical form and the disputed viable-but-not-culturable coccoid form. Infection by the helical form proceeds through the oral-oral route, while that by the coccoid form, if possible at all, is by the faecal-oral and/or the oral-oral route. The present pilot study addresses the question of disinfectant efficacy against both forms of the bacterium.

Chemistry, Pharmaceutical↗
PubMed2001

Targeting the dust.

Explore the source record for details and available documents.

Blood Cell Count↗
PubMed2001

Homozygosity for the C-->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome.

Recently, a C-->T polymorphism at nucleotide 46 in the 5'-untranslated region of the factor XII (FXII) gene was shown to be associated with lower levels of FXII. To study the impact of this polymorphism on the development of an acute coronary syndrome (ACS), we compared 303 patients with ACS and 227 patients with stable coronary artery disease (CAD). In the latter group, 54.2% of individuals carried wild-type FXII:46C, 37.9% were heterozygous FXII:C46T and 7.9% were homozygous for FXII:46T. In contrast, in the ACS group (n = 303), 54.1% were wild-type FXII:46C, 42.6% were heterozygous FXII:C46T and only 3.3% carried the homozygous FXII:46T genotype. The 2.5-fold lower prevalence of the FXII:46T genotype in patients with ACS could indicate a protective effect on the development of ACS (odds ratio = 0.4, 95% CI 0.1-0.9) in patients with pre-existing CAD.

5' Untranslated Regions↗
PubMed2001

Hygiene and health - the need for a holistic approach.

The holistic principles of hygiene and public health have contributed substantially to an increase in life expectancy by more than 30 years and in life quality since the beginning of the 20th century. Frank, Pettenkofer, Nightingale, Pasteur, Lister, and Koch have been pioneering protagonists of the holistic approach to hygiene and public health. Socioeconomic development and related factors such as nutrition status and food hygiene, housing conditions, water supply and sewage systems, and education (including motivation for personal hygiene) have obviously been of more importance for life expectancy and life quality than progress in curative medicine, such as availability of microbial diagnosis, vaccination, and antibiotics. Today, new risk factors for infectious diseases arise, even in developed countries. These risk factors arise from emerging pathogens, antibiotic-resistant microorganisms, changing demographic patterns, an increasing amount of ambulatory and home care, socioeconomic and environmental changes, technical environments, worldwide distribution of food, and changing human behavior with a decreased awareness of microbial threats. These new challenges worldwide make a renewal of the holistic approach of hygiene and public health both urgent and necessary. On the basis of historic experience, policies that focus on surveillance and control, diagnosis, and therapy only can be assumed to be both insufficient and inefficient in controlling the new challenges in infectious diseases. Experiences in Germany with a holistic hospital hygiene strategy since 1976 provide encouragement for the promotion of holistic health concepts. Risk assessment, risk management, and risk communication are basic steps of a modern holistic strategy. Hygiene has the potential to act as a moderator of diverging positions of different disciplines within this renewed approach.

Communicable Disease Control↗
PubMed2001

Reverse transcriptase template switching during reverse transcriptase-polymerase chain reaction: artificial generation of deletions in ribonucleotide reductase mRNA.

Using reverse transcriptase-polymerase chain reaction (RT-PCR), we have recently described a bona fide deletion within the coding sequence of the large subunit of ribonucleotide reductase (R1) mRNA in colon cancer. Consecutive studies have raised questions about the nature of this phenomenon, because the corresponding genomic alteration at the DNA level or an aberrant protein could not be detected. Thus we considered an in vitro artifact during RT-PCR as a possible explanation for this observation. In contrast to reverse transcriptase, Taq DNA polymerase or C. therm DNA polymerase did not generate the aberrant product, suggesting the demand for the template switching activity intrinsic to retroviral reverse transcriptases. In fact, virtually the same deletion was observed in RT-PCR experiments when in vitro transcribed R1 mRNA was used. Considering structural prerequisites for template switching within R1 mRNA, we show that two direct repeats adjacent to a strong stem-loop secondary structure flank the deleted region of 1851 base pairs. Because several mRNAs encoding proteins of clinical and diagnostic importance fulfill these criteria, template switching enhances the potential risk of observing artifacts when interpreting results from RT-PCR studies. As shown in the present example, this may involve the artificial generation and the misinterpretation of PCR fragments amplified from targets relevant to tumor biology or cancer pharmacology. As a possible solution, one-step PCR with C. therm polymerase should be considered. This polymerase eliminates the artificial generation of aberrant mRNA signals observed during cDNA synthesis.

Adenocarcinoma↗
PubMed2001

GIS-based analysis of drinking-water supply structures: a module for microbial risk assessment.

Water-related infections constitute an important health impact world-wide. A set of tools serving for Microbial Risk Assessment (MRA) of waterborne diseases should comprise the entire drinking-water management system and take into account the Hazard Analysis and Critical Control Point (HACCP) concept which provides specific Critical Control Points (CCPs) reflecting each step of drinking-water provision. A Geographical Information System (GIS) study concerning water-supply structure (WSS) was conducted in the Rhein-Berg District (North Rhine-Westphalia, Germany). As a result, suitability of the existing water databases HYGRIS (hydrological basis geo-information system) and TEIS (drinking-water recording and information system) for the development of a WSS-GIS module could be demonstrated. Spatial patterns within the integrated raw and drinking-water data can easily be uncovered by GIS-specific options. The application of WSS-GIS allows a rapid visualization and analysis of drinking-water supply structure and offers huge advantages concerning microbial monitoring of raw and drinking water as well as recognition and investigation of incidents and outbreaks. Increasing requests regarding health protection and health reporting, demands for a better outbreak management and water-related health impacts of global climate change are major challenges of future water management to be tackled with methods including spatial analysis. GIS is assumed to be a very useful tool to meet these requirements.

Environmental Monitoring↗
PubMed2001

A geographical information system (GIS) as a tool for microbial risk assessment in catchment areas of drinking water reservoirs.

The main tributaries of three drinking water reservoirs of Northrhine-Westfalia (Germany) were monitored within a 14-month period mainly for bacterial and parasitic contamination. In this context a detailed geo-ecological characterisation within the differing catchment areas was carried out to reveal a reliable informational basis for tracing back the origin of microbial loads present in the watercourses. To realise a microbial risk assessing geo-ecological information system (MRA-GIS), a Geographical Information System (GIS) has been implemented for the study areas. The results of the microbiological investigations of the watercourses showed an input of pathogens into all three of the tributaries. It could be demonstrated that the use of MRA-GIS database and some GIS-techniques substantially support the spatial analysis of the microbial contamination patterns. From the hygienic point of view, it is of the utmost importance to protect catchment areas of surface water reservoirs from microbial contamination stemming from human activities and animal sources. This constitutes essential part of the multi-barrier concept which stresses the importance of reducing diffuse and point pollution in catchment areas of water resources intended for human consumption. MRA-GIS proves to be helpful to manage multi-barrier water protection in catchment areas and ideally assists the application of the HACCP concept on drinking water production.

Environmental Monitoring↗
PubMed2001

Genistein prevents the glucose autoxidation mediated atherogenic modification of low density lipoprotein.

Hyperglycemia has been assumed to be responsible for oxidative stress in diabetes. In this respect, glucose autoxidation and advanced glycation end products (AGE) may play a causal role in the etiology of diabetic complications as e.g. atherosclerosis. There is now growing evidence that the oxidative modification of LDL plays a potential role in atherogenesis. Glucose derived oxidants have been shown to peroxidise LDL. In the present study, genistein, a compound derived from soy with a flavonoid chemical structure (4', 5, 7-trihydroxyisoflavone) has been evaluated for its ability to act as an antioxidant against the atherogenic modification of LDL by glucose autoxidation radical products. Daidzein, (4',7-dihydroxyisoflavone) an other phytoestrogen of soy, was tested in parallel. Genistein--in contrast to daidzein--effectively prevented the glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive substance formation (TBARS), alteration in electrophoretic mobility, lipid hydroperoxides and fluorescence quenching of tryptophan residues of the lipoprotein. In addition the potential of glucose-oxidized LDL to increase tissue factor (TF) synthesis human endothelial cells (HUVEC) was completely inhibited when genistein was present during LDL oxidative modification by glucose. Both phytoestrogens did not influence the nonenzymatic protein glycation reaction as measured by the in vitro formation of glycated LDL. As the protective effect of genistein on LDL atherogenic modification was found at glucose/genistein molar ratios which may occur in vivo, our findings support the suggested beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.

Cells, Cultured↗