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Biomedical subjects

H Drexler

Publications and source records attributed to H Drexler.

At least 37 records · Page 2Linked to original sources

[PCB in interiors - a relevant health risk?].

Polychlorinated biphenyls (PCB) were manufactured between 1929 and 1989. Due to their great chemical persistence, these substances have been used for many different purposes. These chemical properties, however, caused PCB to accumulate in the food chain and resulted in background exposure of the general population. PCB has also been used as plasticizer for sealants in prefabricated buildings, thus causing problems to the present date. At the end of the 90-ties in a school in Nuremberg, Germany, elevated PCB concentrations were measured in indoor air. Some of these results were higher than 3,000 ng/m(3) which means decontamination according to the German "PCB directive". Press coverage made these results a matter of public debate, so that teachers, school children and parents were highly worried because of possible health effects. The Bavarian Minister for Health, Nutrition and Consumer Protection asked us to examine school children and teachers with regard to their internal PCB exposure and health complaints. A group of school children from a non-contaminated school served as controls. For the determination of PCB levels the plasma samples were blinded before analysis. Lower chlorinated PCB (PCB 28, 52, 101) were detected more often and in higher concentrations in plasma samples of school children of the contaminated school compared to the controls. The plasma levels of the higher chlorinated PCBs (PCB 138, 153, 180) did not show similar differences between exposed and non-exposed school children. The relative PCB doses additionally taken up in the contaminated school were less then 5 % of the background exposure of the children. That is why it could finally be concluded that no appreciable additional health risk may result from inhalation of PCB contaminated indoor air in this school. Due to the design, performance and interpretation of this study, including representatives of parents and teachers, these results were widely accepted by most of the parents who initially had been very concerned about possible health effects.

Air Pollution, Indoor↗

Dimethyl sulphate; a hidden problem in occupational medicine.

BACKGROUND: In a chemical plant, alkylating agents (mainly ethylene oxide and propylene oxide, but also dimethyl sulphate) are utilised for the production of special surfactants. AIMS: To determine possible uptakes of dimethyl sulphate by workers using N-methylvaline. METHODS: Sixty two workers in a chemical plant (38 smokers, 24 non-smokers) with potential exposure to dimethyl sulphate were monitored with respect to their blood levels of N-methylvaline. Ten laboratory workers without exposure to methylating agents were controls. Blood samples of eight workers from a specific working area were analysed for N-methylvaline in a follow up investigation four months later. RESULTS: The 95th centile for N-methylvaline was 80.7 microg/l blood in the exposed workers compared to 12.4 microg/l blood in controls. In a hot spot area, 10 workers exceeded the German exposure equivalent value for dimethyl sulphate (40 microg/l blood) up to fourfold. In contrast, dimethyl sulphate has not been detectable in workplace air in this area. In a follow up investigation of eight of these 10 workers, N-methylvaline levels were significantly lower, but still increased. CONCLUSIONS: The present study is to our knowledge the first to report increased N-methylvaline levels after occupational exposure to dimethyl sulphate. As ambient monitoring values in the plant could not explain this exposure, skin contact was considered to be the main route of uptake for this substance. Dimethyl sulphate may therefore represent an occupational problem that has been generally underestimated in the past.

Adult↗

Skin protection and percutaneous absorption of chemical hazards.

Hazardous substances that penetrate the skin barrier may induce dermal irritation, inflammation or sensitisation, as well as systemically toxic effects. Air threshold limits are insufficient to prevent adverse health effects in the case of contact with substances with a high dermal absorption potential. Biological monitoring is a useful tool to quantify internal exposure of an individual and allows an assessment to be made of the dermal absorption pathway. Additionally, the efficacy of protective equipment can be proved. Standard gloves are ineffective to decrease dermal uptake. Various skin-care products include emulgators, which are used as penetration enhancers in transdermal therapeutic drugs. Hence, specific skin-care products potentially enhance dermal absorption of certain chemicals. On the other hand, the best protection from dermal absorption is the physiological skin barrier-the stratum corneum. Skin-care products that accelerate regeneration of the stratum corneum are obliged to have positive effects to prevent dermal absorption. With regard to the increasing number of occupational skin diseases and the large quantity of skin-care products that are used at workplaces it is essential that the mechanism of protection and efficacy be assessed. In the future, we require evidence-based prevention or evidence-based medicine that includes evidence-based prevention.

Dermatitis, Occupational↗

In vitro evaluation of the efficacy of skin barrier creams and protective gloves on percutaneous absorption of industrial solvents.

OBJECTIVES: The aim of the experiments was to evaluate the efficacy of skin barrier creams (SBCs) and protective gloves and its potential for reduction of percutaneous absorption of industrial solvents. METHODS: We assessed percutaneous absorption of ethylene glycol (EG), isopropyl alcohol (IA) and 1,2,4-trimethylbenzene (TMB), using static diffusion cells. These solvents were applied neat (EG, TMB) as well as in 10% and 50% aqueous solution (EG, IA) or in 10% and 50% ethanol-diluted solution (TMB). Furthermore, we tested the percutaneous absorption of IA mixed in one cleaning agent (CA), used in newspaper printing shops to clean the rollers of printing machines. Additionally, the penetration behaviour of 10% and 50% solutions of EG, IA and TMB was tested. The experiments were carried out on untreated and on SBC-treated excised human skin from one donor, and on protective gloves. Saline was used as receptor fluid for EG and IA, and neat ethanol for TMB. RESULTS: The penetration of 50% EG, IA and TMB solutions through SBC-treated skin was higher than in untreated skin (factor 3.9 for EG, 0.32 for IA and 0.06 for TMB). The penetration of IA in the IA-CA mixture was five-times higher through untreated skin as for the single compound in 10% aqueous solution. In skin, treated with SBC, we found a 17-fold penetration enhancement of IA in the IA-CA mixture. No appreciable penetration of EG and IA was observed through nitrile rubber gloves. CONCLUSIONS: Our in vitro experiments could not demonstrate an efficacy of SBC to protect skin penetration for the tested solvents. The percutaneous absorption of all solvents in 50% solution was increased through skin treated with SBCs. Furthermore, SBCs enhance the penetration rates of solvents from complex mixtures compared with the single solvents. The tested gloves showed sufficient protection for the hydrophilic solvents, but not for TMB.

2-Propanol↗

[Occupationally acquired tuberculosis in an administrative assistant: aspects of an expert report].

HISTORY: Since the age of 48 years an administrative assistant had been treated with immunosuppressive drugs for a mixed connective tissue disease. She was in direct personal contact with newly arrived Africans while working at an admittance centre for refugees. At the age of 53 years the symptoms changed with increasing joint pains and loss of weight. The immunosuppressive therapy with corticoids was increased. A total hip arthroplasty followed. An infection of the wound occurred and many revisions of the scar tissue followed. After a total knee arthroplasty an epileptic seizure occurred. A tuberculous meningoencephalitis was diagnosed. Mycobacterium tuberculosis was detected in urine, sputum and in secretions of different joints. A detailed analysis revealed Mycobacterium tuberculosis var. africanum. At the age of 59 years the patient died during a period of rehabilitation, the clinical signs indicating pulmonary embolism. CONCLUSIONS: The haematogenous spread of Mycobacterium tuberculosis was undoubtedly exacerbated by the immunosuppressive therapy. As a preventive measure a competent occupational consultation could have stopped the occupational exposure to Mycobacteria by transferring the patient during immunosuppressive therapy. The change of symptoms had been misclassified as worsening of the mixed connective tissue disease. Considering legal aspects of the German social insurance system the criteria of an occupational disease would have been fulfilled.

Adrenal Cortex Hormones↗

Current internal exposure to pesticides in children and adolescents in Germany: blood plasma levels of pentachlorophenol (PCP), lindane (gamma-HCH), and dichloro(diphenyl)ethylene (DDE), a biostable metabolite of dichloro(diphenyl)trichloroethane (DDT).

Pesticides are widely used throughout the world in agriculture to protect crops, and in public health to control diseases transmitted by animal vectors or intermediate hosts. After the prohibition of organochlorines such as DDT internal exposure of the general population to the organochlorines has been reduced markedly. Herein, current internal exposure of children and adolescents in an urban area in Germany to PCP, lindane, and DDT/E is reported. One hundred and thirty children and adolescents took part in this voluntary investigation. All of them stated they had never used pesticides in their homes or for medical reasons. Blood plasma was analysed for pentachlorophenol (PCP), lindane (gamma-HCH), and dichloro(diphenyl)ethylene (DDE), a biostable metabolite of dichloro(diphenyl)trichloroethane (DDT), using gas chromatography/electron capture detection according to well established methods approved by the Deutsche Forschungsgemeinschaft. Median (and 95th percentiles) in the age groups < 6, 6- < 12, and 12- < 18 years of age were (microgram/l): DDE: 0.75 (4.45), 0.95 (5.04), 0.89 (8.77); DDT: < 0.1 (0.22), < 0.1 (0.25), < 0.1 (0.30); PCP: 2.48 (17.32), 2.69 (5.85), 2.08 (8.04); lindane: < 0.1 (0.12, < 0.1 (0.08), < 0.1 (0.09). High levels of internal exposure to DDT in two girls were probably obtained during a holiday stay in India; high PCP-levels in two other girls were caused by a leather jacket impregnated with PCP, and a holiday abroad, respectively. Current background levels of internal exposure to organochlorine insecticides in children and adolescents in Germany are quantified. Exposure to these substances in the general population is thought to occur mainly via residues in food, which are low in general, today. In special cases, however, individual exposures may be dominated by other sources, i.e. impregnated leather clothes.

Adolescent↗

Skin strain and its influence on systemic exposure to a glycol ether in offset printing workers.

Under workplace conditions, it is difficult to prove the influence of skin lesions on skin penetration by chemical substances. The aim of the present study was to show whether systemic exposure to glycol ether increases due to lesions of the skin in printing workers. 28 male printers, exposed to 2-(2-butoxyethoxy)ethanol (BEE), were interviewed about the workplace exposure by a standardized questionnaire. The systemic exposure in printers was determined by biological monitoring of the main metabolite of BEE butoxyethoxyacetic acid (BEAA) in urine. Furthermore, clinical examination of the skin, transepidermal water loss, capacitance and skin surface pH measurements were carried out. Erythema and scaliness were the most important factors showing an effect on dermal absorption. The mean urinary BEAA excretions for printers with skin lesions on the hands were higher (20.62 mg/l for scaliness and 14.40 mg/l for erythema) compared to that for printers without detectable skin lesions (12.08 mg/l for scaliness and 13.03 mg/l for erythema). Bioengineering measurements to predict skin strain and percutaneous absorption were only supportive. We were able to show that by using a multiple spectrum of methods an enhancement of percutaneous absorption of BEE could be demonstrated in workers with skin lesions.

Adult↗

Cardiovascular function of workers exposed to carbon disulphide.

OBJECTIVES: The aim of the study was to verify that exposure to carbon disulphide (CS(2)) up to 10 ppm results in a negative inotropic effect on cardiovascular function. METHODS: In a cross-sectional study a total of 325 workers exposed to CS(2) in the rayon-producing industry and 179 controls from the same plants were examined. The exposure assessment was based on personal air sampling and biological monitoring (2-thiothiazolidine-4-carboxylic acid (TTCA) in urine) for all persons. The examination consisted of a standardised questionnaire, physical examination, assessment of body fat mass, ergometric test with the determination of work capacity at heart rates of 100, 130, 150 and 170 beats/min, and electrocardiography. RESULTS: The mean external exposure was 6.04 ppm CS(2) (range: 0.03-91.08); the mean internal exposure was 1.14 mg TTCA/g creatinine (range: 0.02-11.50). The workers exposed to CS(2) showed better physical fitness. The diameters of the left heart chamber of the exposed persons were not significantly different when compared with occupationally non-exposed workers, but there was a tendency of increasing diameters for the exposed employees. In the multiple linear regression the diameters showed physiologically plausible correlations with the body mass index, body fat mass, alcohol consumption, and physical fitness, but not, however, with the exposure, neither with the exposure group in all persons nor with the internal or external exposure within the exposed workers. CONCLUSIONS: In this study, differences in the heart chamber diameters between exposed persons and controls could not be confirmed. Differences in physical fitness and constitution can explain differences in heart chamber diameters.

Adult↗

New gas chromatographic-mass spectrometric method for the determination of urinary pyrethroid metabolites in environmental medicine.

We have developed and validated a new, reliable and very sensitive method for the determination of the urinary metabolites of the most common pyrethroids in one analytical run. After acidic hydrolysis for the cleavage of conjugates, the analytes cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-Cl(2)CA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (trans-Cl(2)CA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Br(2)CA), 4-fluoro-3-phenoxybenzoic acid (F-PBA) and 3-phenoxybenzoic acid (3-PBA) were extracted from the matrix with a liquid-liquid extraction procedure using n-hexane under acidic conditions. For further clean-up, NaOH was added to the organic phase and the carboxylic acids were re-extracted into the aqueous phase. After acidification and extraction into n-hexane again, the metabolites were then derivatised to volatile esters using N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamid (MTBSTFA). Separation and detection were carried out using capillary gas chromatography with mass-selective detection (GC-MS). 2-Phenoxybenzoic acid (2-PBA) served as internal standard for the quantification of the pyrethroid metabolites. The limit of detection for all analytes was 0.05 microg/l urine. The RSD of the within-series imprecision was between 2.0 and 5.4% at a spiked concentration of 0.4 microg/l and the relative recovery was between 79.3 and 93.4%, depending on the analyte. This method was used for the analysis of urine samples of 46 persons from the general population without known exposure to pyrethroids. The metabolites cis-Cl(2)CA, trans-Cl(2)CA and 3-PBA could be found in 52, 72 and 70% of all samples with median values of 0.06, 0.11 and 0.16 microg/l, respectively. Br(2)CA and F-PBA could also be detected in 13 and 4% of the urine samples.

Adolescent↗

Quality assurance of biological monitoring in occupational and environmental medicine.

Biological monitoring of chemical exposure in the workplace has become increasingly important in the assessment of health risk as an integral part of the overall occupational health and safety strategy. In environmental medicine biological monitoring plays also an important role in the assessment of excessive, acute or chronic exposure to chemical agents. To guarantee that the results obtained in biological monitoring are comparable with threshold limit values and results from other laboratories, the analysis must be carried out with tested and reliable analytical methods and accompanied by a quality assurance scheme. Confounding influences and interferences during the pre-analytical phase can be minimised by recommendations from experienced laboratories. For internal quality control commercially available control samples with an assigned concentration are used. External quality control programs for biological monitoring are offered by several institutions. The external quality control program of the German Society of Occupational and Environmental Medicine has been organised since 1982. In the meantime the 27th program has been carried out offering 96 analytes in urine, blood and plasma for 47 substances. This program covers most of the parameters relevant to occupational and environmental medicine. About 350 laboratories take part in these intercomparison programs. At present, ten German and 14 international laboratories are commissioned to determine the assigned values. The data evaluated from the results of the intercomparison programs give a good overview of the current quality of the determination of analytes assessed in occupational and environmental toxicological laboratories. For the analysis of inorganic substances in blood and urine the tolerable variation ranges from 7.5 to 43.5%. For organic substances in urine the tolerable variation ranges from 12 to 48%. The highest variations (36-60%) were found for the analysis of organochlorine compounds in plasma. The tolerable variations for the determination of solvents in blood by head space gas chromatography range from 26 to 57%. If the recommendations for the pre-analytical phase, the selection of reliable analytical methods by the laboratory and the carrying out of adequate quality control are observed, the pre-requisites for reliable findings during biological monitoring are fulfilled

Chromatography↗

When should a substance be designated as sensitizing for the skin ('Sh') or for the airways ('Sa')?

In the List of MAK and BAT Values compounds are designated with 'Sa' ('sensitizing for the airways') or 'Sh' ('sensitizing for the skin') if, according to scientific evidence, they are allergens. Mainly based on suggestions by a WHO working group and based on our own experience, extended criteria have been elaborated by the working group 'skin and allergy' of the Commission of the Deutsche Forschungsgemeinschaft for the Investigation of Health Hazards of Chemical Compounds in the Work Area, which are presented in this article. They serve as guidelines for deciding which substances have to be labelled 'Sa' and 'Sh', respectively, for the prevention of sensitization and subsequent allergic diseases in workers. Although in some special cases their strict application may not be deemed necessary or possible, the proposed new criteria should be used to make the procedure of classification of substances: 1) more rational, 2) more consistent, 3) more comprehensible, and 4) more transparent. This paper informs readers working scientifically or administratively in this field and invites a critical discussion of the issue.

Allergens↗

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Angiotensin-Converting Enzyme Inhibitors↗

Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: role of superoxide dismutase.

BACKGROUND: Flow-dependent, endothelium-mediated vasodilation (FDD) and activity of extracellular superoxide dismutase (EC-SOD), the major antioxidative enzyme of the arterial wall, are severely impaired in patients with coronary artery disease (CAD). We hypothesized that both ACE inhibitor (ACEI) and angiotensin II type 1 receptor antagonist (AT(1)-A) increase bioavailability of nitric oxide (NO) by reducing oxidative stress in the vessel wall, possibly by increasing EC-SOD activity. METHODS AND RESULTS: Thirty-five patients with CAD were randomized to 4 weeks of ACEI (ramipril 10 mg/d) or AT(1)-A (losartan 100 mg/d). FDD of the radial artery was determined by high-resolution ultrasound before and after intra-arterial N-monomethyl-L-arginine (L-NMMA) to inhibit NO synthase and before and after intra-arterial vitamin C to determine the portion of FDD inhibited by oxygen free radicals. EC-SOD activity was determined after release from endothelium by heparin bolus injection. FDD was improved after ramipril and losartan (each group P<0.01), and in particular, the portion of FDD mediated by NO, ie, inhibited by L-NMMA, was increased by >75% (each group P<0.01). Vitamin C improved FDD initially, an effect that was lost after ramipril or losartan. After therapy, EC-SOD activity was increased by >200% in both groups (ACEI, 14.4+/-1.1 versus 3.8+/-0.9 and AT(1)-A, 13.5+/-1.0 versus 3.9+/-0.9 U. mL(-1). min(-1); each P<0.01). CONCLUSIONS-Four weeks of therapy with ramipril or losartan improves endothelial function to similar extents in patients with CAD by increasing the bioavailability of NO. Our results suggest that beneficial long-term effects of interference with the renin-angiotensin system may be related to reduction of oxidative stress within the arterial wall, mediated in part by increased EC-SOD activity.

Angiotensin Receptor Antagonists↗