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S Scharf

Publications and source records attributed to S Scharf.

At least 19 recordsLinked to original sources
PubMed2006

Transcription linked to recombination: a gene-internal promoter coincides with the recombination hot spot II of the human MLL gene.

The MLL gene is frequently involved in chromosomal translocations associated with high-risk acute leukaemia. Infant and therapy-related acute leukaemia patients display chromosomal breakpoints preferentially clustered in the telomeric portion of the MLL breakpoint cluster region (SCII). Here, we demonstrate that SCII colocalizes with a gene-internal promoter element in the mouse and human MLL gene, respectively. The mRNA generated encodes an N-terminally truncated version of MLL that still exhibits many functional regions, including the C-terminal SET-domain. Etoposide-induced DNA double-strand breaks colocalize with the binding site of RNA polymerase II and the transcription initiation region, but not with a nearby Topo II consensus sequence. Thus, the observed genomic instability of the human MLL gene is presumably linked to transcriptional processes. The consequences of this novel finding for the creation of chromosomal translocations, the biology of the MLL protein and for MLL-mediated acute leukaemia are discussed.

Animals↗
PubMed2005

Fine particles and meteorological conditions are associated with lung function in children with asthma living near two power plants.

Fine particles are thought to pose a risk to health, especially for vulnerable groups such as children with asthma. These children are also known to be affected by meteorological and seasonal changes. We assessed the association between air pollution and lung function via peak expiratory flow (PEF), controlling for seasonal changes, meteorological conditions and personal physiological, clinical and sociodemographic measurements, in a panel of schoolchildren with asthma living near two power plants in Israel. Two hundred and eighty-five children with confirmed asthma performed PEF tests and completed a respiratory symptoms diary twice a day. Particulate matter <10 microm in diameter (PM10), particulate matter <2.5 microm in diameter (PM2.5) and meteorological conditions were measured at six fixed stations. Data were analysed using time series analysis-generalized linear model and generalized estimating equations. The models were built under the assumption that any health outcome belongs to a multivariate hierarchical system and depends on meteorological, geophysical and sociocultural variables and pollution factors. No significant differences were found in the demographic (age, gender, mean parental education level, parental smoking habits, place of birth and housing density), physiological (body mass index) and clinical factors (illness severity) between the communities participating in the study. A significant direct effect of PM2.5 on the PEF was found in Ashdod (P=0.000). In Sderot, this effect was through an interaction between PM10 and the sequential day of the year (P=0.000). The main conclusion of this study is that children with asthma are at risk from air pollution and geophysical conditions. Policy makers should take these results into consideration when setting thresholds for environmental protection.

Air Pollutants↗
PubMed2004

Monitoring of selected estrogenic hormones and industrial chemicals in groundwaters and surface waters in Austria.

In order to address the Austrian situation concerning endocrine disrupting substances (EDS), a consortium called Austrian Research Cooperation on Endocrine Modulators (ARCEM) was established in 1999. Among several other issues that were investigated, ARCEM monitored more than 400 ground- and surface water samples for selected estrogenic hormones and industrial chemicals. Appropriate analytical methods were established using GC-HRMS for the detection of hormones and LC/MSMS for the detection of industrial chemicals. Since analytical results were forwarded for toxicological assessments within the programme, quantification limits below 0.1 ng/l (ethinyl estradiol) and 10 ng/l (industrial chemicals) were required depending on the NOEL of the individual compound. Results indicate that both hormones and industrial chemicals occur in the selected ground- and surface water sites in detectable concentrations. Three river sites were identified as being charged with noticeable concentrations of EDS. These results were verified by biological indications within the part of the ARCEM programme dealing with bio-indications.

Austria↗
PubMed2004

Analysis of nonylphenol polyethoxylates and their metabolites in water samples by high-performance liquid chromatography with electrospray mass spectrometry detection.

Evidence that some alkylphenol polyethoxylates (APEOs) breakdown products are estrogenic has intensified the interest over their environmental and human health effects. Different quantitative methods but one single preparation and extraction method for the analysis of nonylphenol polyethoxylates (NPEOs) and their metabolites in water samples using solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) with electrospray mass spectrometry detection (ESI-MS), are described. Quantification limits range about the low ng/l for the enrichment of 500 ml water samples and mean recoveries of 70% are achieved. These methods were subsequently applied to water samples coming from Austrian treatment plants.

Austria↗
PubMed2004

Endocrine disrupters in the aquatic environment: the Austrian approach--ARCEM.

A consortium of Austrian scientists (ARCEM) carried out a multidisciplinary environmental study on Austrian surface and ground waters including chemical monitoring, bioindication, risk assessment and risk management for selected endocrine disrupters: 17beta-estradiol, estriol, estrone, 17alpha-ethinylestradiol, 4-nonylphenol, 4-nonylphenol ethoxylates (4-NP1EO, 4-NP2EO) and their degradation products, ocytlphenol, ocytlphenol ethoxylates (OP1EO, OP2EO) as well as bisphenol A. To obtain data representative for Austria, a material flow analysis served to select relevant compounds and water samples were collected monthly over one year at those sites routinely used in Austrian water quality control. The following results were obtained and conclusions drawn: 1. Chemical monitoring: As compared to other countries, relatively low levels of pollution with endocrine disrupters were detected. 2. Bioindication: In the surface waters under study, male fish showed significant signs of feminization and demasculinization (increased production of the egg-yolk protein and histological changes of the gonads. 3. Risk assessment: For humans, exposure via either drinking water abstraction (ground water) or fish consumption was considered. The exposure levels of the compounds under study were below those considered to result in human health risks. Likewise, for bisphenol A and octylphenols, there was no indication for risk posed upon the aquatic environment (fish). However, nonylphenol or 17alpha-ethinylestradiol exposure along with results of bioindication (2) suggest a borderline estrogenic activity in a considerable number of surface waters. Consequently the emissions of these substances into the surface waters affected have to be reduced. 4. Risk management: Waste water treatment experiments revealed a positive correlation between the removal rate of endocrine disrupters from the waste water and the sludge retention time in the treatment plants. These substances are removed to a higher extend at low loaded plants designed for nutrient removal than at plants that remove carbon and/or employ nitrification only. As to drinking water treatment, chlorine dioxide and ozone were found to eliminate all investigated substances, except nonylphenol ethoxylates. (For the complete study see: www.arcem.at)

Animals↗
PubMed2001

Sources and behaviour of bismuth active substances (BiAS) in a municipal sewage treatment plant.

Non-ionic surfactants are widely used for household and industrial purposes. For different reasons the metabolites, e.g. 4-nonylphenol, nonylphenol monoethoxylate, nonylphenol diethoxylate and 4-tert-octylphenol, are especially considered to be endocrine disruptive and thus potentially harmful for the environment. In this study, field samples of raw wastewater from different point sources, including industrial effluents, household effluents, the influent and secondary effluent of a wastewater treatment plant that treats this wastewater were monitored simultaneously. Composite samples were taken five times over periods of 1 week at nine sample sites. The results showed that the concentrations and fluxes were varying. In addition industrial, influent and effluent samples were investigated for nonylphenol (NP). The highest concentrations of bismuth active substances (BiAS) were obtained by wastewater samples from a chemical and a cloth washing company ranging from 10,200 to 65,600 microg/l and 14,600 to 33,900 microg/l BiAS, respectively. Although the concentration of BiAS in the wastewater of the paper production was only between 460 and 1200 microg/l BiAS, the NP/BiAS ratio of 0.51% was considerably higher than in other industrial effluents. The BiAS concentration in wastewater samples from households ranged from 2200 to 7900 microg/l BiAS, but the NP concentration was quite low, 0.01% of BiAS. This could be due to the effort within the EU to phase out nonylphenol polyethoxylates in household detergents. Influent concentrations between 700 and 2200 microg/l BiAS with removal rates in the WWTP ranging from 70.7 to 99.4% with an average of 92.2% could be measured.

Bismuth↗
PubMed2000

Bisphenol A: emissions from point sources.

Bisphenol A is widely used for the production of epoxy resins and polycarbonate plastics. Special in vitro test systems and animal experiments showed a weak estrogenic activity for Bisphenol A. Based on in vitro receptor interaction studies, the activity was estimated to be 2 x 10(-3) lower than that of estradiol. Especially aquatic wildlife could be endangered by waste water discharges. To manage possible risks arising from Bisphenol A contamination, the major fluxes need to be obtained and the contributors to the contamination of municipal treatment plants need to be determined. In this study, industrial emitters and communal waste waters were monitored simultaneously. Mixed samples were taken over periods of one week at nine sample sites. The results showed that the concentrations and fluxes were variable. The paper industry was the major Bisphenol A contributor to the influent of the waste water treatment plant. All the other fluxes measured, including two household areas, were considerably low. About 90% of the total load was removed during the waste water treatment.

Austria↗
PubMed2000

Reduced-time-window sestamibi scanning for nonlocalized primary hyperparathyroidism.

BACKGROUND: Technetium Tc 99m sestamibi scan is the standard of care for localizing parathyroid adenomas. METHODS AND MATERIAL: We performed a retrospective, single-institution study of 111 consecutive patients with primary hyperparathyroidism who underwent standard sestamibi scan for localization of a parathyroid lesion. A revised protocol of reduced-time-window sestamibi scan was used in nonlocalized patients. The protocol was composed of single-view scans at 15, 30, 45, and 120 minutes and tomograms at 60 minutes. RESULTS: Thirty-five patients underwent surgery at our institution. Thirty-one had adenomas, and 4 had hyperplasia. Three of 31 patients did not show localization on the standard scan and underwent reduced-time-window scans, which localized 2 more adenomas. These were confirmed at the time of surgery. CONCLUSION: We suggest that all patients with a high degree of suspicion for a parathyroid adenoma, which is not visualized by a standard scan, undergo a reduced-time-window scan.

Adenoma↗
PubMed1999

A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease.

BACKGROUND: Previous studies suggest a potential benefit from nonsteroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD). Prescribing NSAIDs, however, carries the risk of significant gastrointestinal adverse events. OBJECTIVES: To study whether treatment with an NSAID prevents expected decline in AD patients and evaluate whether co-administration of the gastro-protective agent, misoprostol, with an NSAID is safe in AD. METHODS: The efficacy and safety of diclofenac in combination with misoprostol (D/M) was evaluated in 41 patients with mild-moderate AD in a prospective 25-week, randomized, double-blind placebo-controlled trial. Efficacy measures comprised the Alzheimer's Disease Assessment Scale cognitive and noncognitive subsections, Global Deterioration Scale, Clinical Global Impression of Change, Mini-Mental State Examination, Instrumental Activities of Daily Living, Physical Self-Maintenance Scale, and a caregiver-rated Global Impression of Change. RESULTS: There were no group differences with any of the outcome measures in an intent-to-treat analysis. There were some nonsignificant trends for the placebo group to have deteriorated more than the D/M-treated patients. Withdrawal rates were 12 of 24 in the D/M group and 2 of 17 in the placebo group. There were no serious drug-related adverse events. CONCLUSIONS: This pilot study, with small treatment numbers, did not demonstrate a significant effect of NSAID treatment in AD, but the trends observed justify further investigations with a larger number of participants. D/M is safe in AD patients, but its tolerability is not optimal.

Aged↗
PubMed1999

Vitamin B6 biosynthesis: formation of pyridoxine 5'-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose-5-phosphate by PdxA and PdxJ protein.

In Escherichia coli the coenzyme pyridoxal 5'-phosphate (PLP) is synthesised de novo by a pathway that is thought to involve the condensation of 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose, catalysed by the enzymes PdxA and PdxJ, to form either pyridoxine (vitamin B6) or pyridoxine 5'-phosphate (PNP). Here we show that incubation of PdxJ with PdxA, 4-(phosphohydroxy)-L-threonine, NAD and 1-deoxy-D-xylulose-5-phosphate, but not 1-deoxy-D-xylulose, results in the formation of PNP. The PNP formed was characterised by (i) cochromatography with an authentic standard, (ii) conversion to pyridoxine by alkaline phosphatase treatment, and (iii) UV and fluorescence spectroscopy. Furthermore, when [2-(14)C]1-deoxy-D-xylulose-5-phosphate was used as a substrate, the radioactivity was incorporated into PNP. These results clarify the previously unknown role of PdxJ in the de novo PLP biosynthetic pathway. The sugar used as substrate by PdxJ is 1-deoxy-D-xylulose-5-phosphate rather than the previously assumed 1-deoxy-D-xylulose. The first vitamin B6 vitamer synthesised is PNP, and not pyridoxine.

Alkaline Phosphatase↗
PubMed1999

Sharps injuries: defining prevention priorities.

OBJECTIVE: An institutional review of sharps injuries was conducted to assist in establishing priorities for resource allocation in a sharps prevention program. DESIGN: A retrospective review of 221 sharps injuries occurring during a 1-year period was conducted by a 4-member multidisciplinary team. Each injury was categorized as either moderate/high, low, or unknown risk for acquisition of bloodborne diseases by using modified provincial definitions of occupational risk for exposure to bloodborne pathogens. RESULTS: A total of 119 injuries were considered to be moderate/high risk, and 93 were at low risk for acquisition of bloodborne disease. Nine injuries could not be categorized. In 59% of high-risk injuries, education or changes in technique were identified as the primary preventive intervention. Passive devices such as needleless intravenous administration sets could theoretically address prevention of the majority of low-risk injuries. Known available safety devices could have prevented 33 (28%) high-risk injuries. CONCLUSION: Disposition of resources must take into consideration the risk of bloodborne disease acquisition and the efficiency and expense of the preventable methods employed. Institutional review of injuries combined with a cost analysis revealed that resources were best allocated to protective devices at source (eg, safety syringes) and on a comprehensive, multidisciplinary, and sustained educational program. Needleless intravenous infusion sets would mainly prevent low-risk injuries at significant cost.

British Columbia↗
PubMed1998

[Investigating chest pain--is there a gender bias?].

Ischemic heart disease (IHD) is women is characterized by a higher morbidity and mortality in the peri-infarction and coronary bypass peri-operative periods. These epidemiological data strengthen our impression that the health system unintentionally "ignores" the high proportion of females with IHD. The process of investigating chest pain, diagnosing IHD, and the subsequent treatment and rehabilitation, seem to differ between the genders. Time elapsed from beginning of chest pain to diagnosis of IHD seems to be longer in women than in men. Personal, educational and social factors are contributory. Although time elapsed between diagnosis and rehabilitation is usually similar in the genders, peri-operative morbidity and mortality are higher in women. It may be that the higher rates in women are caused by delay in diagnosis and treatment, which allows worsening of the disease in women before treatment. This delay can occur during the time needed for evaluation of chest pain, from the door of the physician to diagnosis and treatment. In our retrospective study we determined the difference in referral of men and women with chest pain to the emergency department (ED) and the attitude of physicians in the ED and medical department to chest pain in men and in women, including final diagnosis on discharge. 615 patients over 18 years referred to the ED for chest pain during 3 randomly chosen, consecutive months were studied. We found that women constituted only 39.5% of the referred patients, but the proportion hospitalized was similar to that in men. Hospitalized women were older (57.7 +/- 18.4 versus 49.7 +/- 17.8 years in men), and had more risk factors (4 versus 2 in men). Proportions of specific diagnoses on discharge from hospital were equal in the genders. To bridge the differences and to implement education in prevention, investigation and treatment of IHD in women, we established the "Female Heart" clinic. The objective of this clinic is to reduce differences in the first step, in the process of evaluating chest pain in women, by educating and encouraging them to present early to their physicians, and by changing physicians' attitudes in the investigation of chest pain in women. We plan to determine in a prospective study if these goals are reached.

Age Factors↗
PubMed1998

Serum interleukin-6 and interleukin-6 soluble receptor in Alzheimer's disease.

Serum levels of interleukin-6 (IL-6) and interleukin-6 soluble receptor (IL-6sR) were measured in 41 patients (23 female and 18 male, mean age 72.5 years) with Alzheimer's disease (AD) and in 32 controls (14 women and 18 men, mean age 69.2 years) using enzyme-linked immunosorbent assays (ELISA). Proportions of individuals with detectable serum IL-6 concentrations did not differ significantly between patients and controls. There was however, a significant decrease in IL-6sR levels in Alzheimer's patients when compared with controls. Our results suggest that there is a dysregulation of IL-6 and its soluble receptor in AD.

Aged↗
PubMed1998

The toilet as a transmission vector of vancomycin-resistant enterococci.

An elderly woman, admitted to the intensive care unit of a large university teaching hospital, was found to be colonized with vancomycin-resistant enterococci leading to the temporary closure of the unit. She had acquired the organism nosocomially, most likely from an environmental source, which had been contaminated when the toilet of a former patient, also colonized with vancomycin-resistant enterococci, had become blocked and overflowed throughout his and the adjoining room. This is the first report of a hospital toilet as the transmission vector for vancomycin-resistant enterococci.

Aged↗
PubMed1998

Epidemic keratoconjunctivitis outbreak at a tertiary referral eye care clinic.

An outbreak of epidemic keratoconjunctivitis (EKC) occurred at a tertiary referral eye care clinic between late September and mid-November 1995. Before the outbreak, instruments were cleaned with 70% isopropyl alcohol and handwashing between patients was not routine. Infection control measures were implemented when the outbreak was recognized in mid-October. Control measures included triaging suspected cases to a separate waiting area, cohorting cases to a specific examining room, endorsing the use of gloves and handwashing during examinations of patients, and cleaning instruments with a buffered bleach solution. Thirty-six cases were diagnosed before the infection control measures were taken, and 3 cases were seen after the control measures were taken. Also, numerous secondary cases occurred in the community. No additional cases were diagnosed from DEcember to February 25, 1996. Acquisition of the infection was linked to visits to 4 of 20 physicians in the eye clinic with 61% of cases associated with visits to 1 of those 4 physicians. The use of diagnostic lenses applied directly to the eye was associated with infection (odds ratio = 2.83, 95% confidence interval = 0.79 to 10.4), although this did not reach statistical significance. The use of tonometers, ophthalmic solutions, or laser therapy was not associated with infection, and all environmental cultures were negative. This outbreak emphasizes the need for implementation of routine infection control guidelines to prevent nosocomial transmission of epidemic keratoconjunctivitis and stresses the need for appropriate disinfection of instruments.

Adenoviridae Infections↗
PubMed1998

NSAIDs and faecal blood loss in elderly patients with osteoarthritis: is plasma half-life relevant?

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) vary in their degree of gastrointestinal (GI) toxicity. NSAIDs with longer half-lives are of particular concern as they may be more toxic in the elderly. AIM: To compare the GI toxicity, by measurement of faecal blood loss, of short, intermediate and long half-life NSAID treatments compared with control in elderly patients with osteoarthritis. METHODS: Twenty-three patients, mean age 69 years, with osteoarthritis requiring NSAID treatment, received treatment with diclofenac 100 mg/day, naproxen 750 mg/day and piroxicam 20 mg/day, representing a short, medium and long half-life NSAID respectively, in a double-blind, randomised, three way, cross-over block design. In each case, a three week washout control phase was followed by active treatment phases of two weeks each with three week washout between treatment phases. RESULTS: Faecal blood loss, collected over 72 hours at the end of each treatment phase, was measured by 51Cr-labelled erythrocyte method. Comparison was made of mean 24 hour faecal blood loss with each treatment compared with control using repeated measures analysis of variance. Eighteen patients completed all phases of the study. Three patients were withdrawn due to GI bleeding; two during diclofenac treatment and one during treatment with piroxicam. Mean 24 hour faecal blood loss with diclofenac (0.53 mL +/- 0.21) was not significantly different from control (0.28 mL +/- 0.06), whereas it was significantly increased with naproxen (2.76 mL +/- 2.22) and piroxicam (1.16 mL +/- 0.62), p = 0.0013. CONCLUSION: A short half-life NSAID was associated with lower GI toxicity than a medium and long half-life NSAID, as measured by faecal blood loss.

Aged↗