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Biomedical subjects

M Døssing

Publications and source records attributed to M Døssing.

At least 91 records · Page 5Linked to original sources

Antipyrine clearance during occupational exposure to styrene.

Animal experiments have indicated that styrene, which is a widely used organic solvent, may induce the microsomal enzyme function of the liver. Thirteen workers with long-term exposure to styrene in a polyester plant were investigated. They worked at air concentrations about the maximal allowed time-weighted average concentration of styrene in most Western countries (50 ppm). The clearance of antipyrine was determined from saliva concentrations before and after three weeks free of exposure and then again three weeks after returning to work. Thirteen matched controls were investigated with similar intervals and methods. No significant differences were found between the half life, apparent volume of distribution, or clearance of antipyrine either within the groups or between the groups. The data exclude (95% confidence limit) the possibility that occupational exposure to styrene at concentrations about 50 ppm stimulates the microsomal enzyme function of the liver to a degree compatible with an increase in antipyrine clearance of more than 2 ml x min-1 (3%). While the first antipyrine estimation was carried out under medical supervision, the workers themselves managed to perform the antipyrine test correctly after verbal and written instructions. This has broadened the application of the antipyrine test.

Adolescent↗

Determination of urinary hippuric acid and o-cresol, as indices of toluene exposure, by liquid chromatography on dynamically modified silica.

Two simple and sensitive high-performance liquid chromatographic methods for the determination of hippuric acid and o-cresol in urine have been developed. The chromatographic system is the same for the two methods and is based on dynamically modified silica. The detection limits were found to be 0.05 mg/ml and 0.05 microgram/ml of urine for hippuric acid and o-cresol, respectively, when using UV detection at 254 nm. The recovery for hippuric acid was about 100% and for o-cresol 33-36%. The detection limit for o-cresol could be lowered by a factor of ten by using fluorescence detection. The methods were used for investigations of the urine from persons exposed to 100 ppm toluene for 6.5 h. The method for o-cresol may also be used for determination of other phenols in urine.

Age Factors↗

Hepatic microsomal enzyme function in technicians and anesthesiologists exposed to halothane and nitrous oxide.

It is controversial whether daily occupational exposure to halothane stimulates (induces) the hepatic microsomal enzyme function in man. We investigated two groups of persons with different degrees of exposure to halothane: Six technicians who for years had been employed with repair and control of anesthesiologic equipment resulting in exposure to about 7 ppm of halothane and 50 ppm of nitrous oxide, and seven anesthesiologists exposed during months to about 2 ppm of halothane and 75 ppm of nitrous oxide. The clearance of antipyrine was determined from saliva concentrations before and 4 wk after discontinuation of exposure. Matched control persons were investigated simultaneously. No significant differences were found between the half-life, apparent volume of distribution, or clearance of antipyrine either within the groups or between the groups. If the antipyrine data from both exposure groups are compared to those of the control groups, the data exclude (95% confidence limit) that antipyrine metabolism increased by more than 3% during exposure to waste anesthetics. This indicates that occupational exposure to halothane in concentrations above the proposed maximal time weighted average concentration of 2 ppm does not change the microsomal activity.

Adult↗

Changes in hepatic microsomal enzyme function in workers exposed to mixtures of chemicals.

Antipryine clearance was measured during occupational exposure and after an exposure-free interval of 3 wk in 26 spray painters, 44 workers in a herbicide-producing (phenoxyacids) plant, and 10 pesticide-exposed greenhouse gardeners. A control group of 39 workers were investigated simultaneously. A noninvasive simplified antipyrine clearance was used. Antipyrine clearance was greater in pesticide-exposed persons, but it was 15% less in workers exposed to spray paints compared to 3 wk after discontinuation of exposure. Clearance was unchanged in the control group examined at the same interval. Thus, the combined action of different spray paints, grinding dust, and cleaners may inhibit, and phenoxyacids, chlorophenols, and various pesticides may induce, the microsomal enzyme function. The workers had been exposed to the chemicals for years, but the change in antipyrine clearance apparently was reversible.

Adolescent↗

A simple method for determination of antipyrine clearance.

Antipyrine clearance (Cl(AP)) is widely used for assessment of microsomal liver function. The usual procedure involves collection of 4 to 7 samples of plasma or saliva obtained during 24 to 48 hr. To determine whether this procedure could be simplified it was compared with one based on a single sample (sCl(AP)) and an estimated volume of distribution (V(D)) in 142 persons. VD was estimated from body weight, in kilograms (BW), height, in centimeters (BH), age in years, and sex, or assumed to be 40 l. The agreement between values of Cl(AP and sCl(AP) increased with the time of the single sample and the two clearance estimates were nearly identical in all cases when the sample was taken after 18 hr. The method used for assessment of V(D) had only a small influence on the agreement. It is suggested that antipyrine clearance (in ml/min) is estimated as (formula: see text) where D is the dose of antipyrine (in mg), c(t) the concentration of antipyrine (in mg/t) at sampling time t (in min), t should be about 1440 min (24hr), and V(D) (in l) is calculated as 0.2363 X BW + 0.1962 X BH - 0.0272 X age - 10.26 (women) or 0.3625 X BW + 0.2239 X BH - 0.1387 X age - 14.47 (men). Little information is lost, however, if a fixed volume of 40 l is used. Then, if the dose is l gm, c(t) is expressed in milligrams per liter, and the sampling time is 24 hr, sCl(AP) = (3.28 - ln c(t)) X 28 ml/min.

Adult↗

Formaldehyde induced symptoms in day care centers.

A questionnaire study among 70 employees at seven mobile day care centers where urea formaldehyde glued particle board has been used for indoor paneling and among 34 employees at three control institutions selected at random where no particle board has been used as building materials, showed a significantly higher frequency of the following symptoms among the staff at the mobile institutions: mucous membrane irritation, headache, abnormal tiredness, menstrual irregularities and use of analgetics (p less than 0.01). As there was no difference in the age distribution or smoking habits of the two groups working in day care institutions from the same geographical locations, we are, therefore, of the opinion that the differences in the frequency of symptoms discovered must be attributed to the differences in the indoor climate conditions prevalent in the institutions. The median concentration of formaldehyde in the mobile institutions was 0.43 mg/m3 in contrast to a concentration in the control institutions of about 0.08 mg/m3. We assume, therefore, that the higher concentration of formaldehyde in the mobile institutions was a cause of the increased frequency of symptoms among the staff. The National Health Service should be aware of the fact that non-specific symptoms such as headache and abnormal tiredness can be the result of unfavorable indoor climate conditions due to the presence of formaldehyde in building materials.

Air Pollutants↗

Drug-induced liver disease in Denmark. An analysis of 572 cases of hepatotoxicity reported to the Danish Board of Adverse Reactions to Drugs.

During the decade 1968-1978 the Danish Board of Adverse Reactions to Drugs received 572 (6% of the total number) reports on hepatotoxicity. Halothane amounted to one fourth of the reported cases. Among the 94 psychotropic-induced adverse drug reactions 54 cases were attributed to chlorpromazine, 10 to tricyclic antidepressants, and only 2 to benzodiazepines. Considering the drug consumption data, the combination trimethoprim-sulfamethoxazole is nearly five times more frequently associated with hepatotoxicity than administration of sulfamethizole. Almost two thirds of the hepatotoxic reactions were classified as cytotoxic. Halothane, oxyphenisatin, rifampicin, alfa-methyldopa, papaverine, phenytoin, and ajmaline were almost exclusively related to cytotoxic reactions. Excluding the halothane-induced hepatotoxic reactions, the relative mortality of the cytotoxic (6%) reactions is not significantly different from that of the cholestatic (3%) ones. Thirteen percent of the patients with halothane-induced hepatotoxicity died.

Adolescent↗

Cimetidine clearance and bioavailability in hepatic cirrhosis.

Nine patients with compensated alcoholic and nonalcoholic cirrhosis of the liver and 11 patients with peptic ulcer received 200 mg of cimetidine orally and intravenously. No differences were observed in cimetidine clearance between the group with peptic ulcer (556 +/- 44 ml/min, mean +/- SEM) and the group with cirrhosis (606 +/- 64 ml/min). The bioavailability of cimetidine was unchanged (84 +/- 4% and 97 +/- 7%). In the patients with cirrhosis, cimetidine clearance did not correlate with galactose elimination capacity or antipyrine clearance. Cimetidine clearance was related to creatinine clearance only when both groups were considered. A reduction of cimetidine dose in patients with compensated cirrhosis appears unwarranted.

Administration, Oral↗

Chelatable lead body burden (by calcium-disodium EDTA) and blood lead concentration in man.

The cheletable part of lead body burden was measured in 32 workers and seven office workers after an infusion test with CaNa2EDTA. The workers had been exposed to lead at a lead and zinc processing unit for one to three years (mean one year). There was good correlation (r = 0.87) between blood lead and chelatable urinary lead excretion described by the equation y = 0.07 . 10(0.46.x). From this equation it can be predicted that the generally accepted limit value for chelatable urinary lead excretion, 0.42 mumol/mmol CaNa2EDTA administered per 24 hours (3.1 mumol/24 hours or 650 micrograms/24 hours), corresponds to a blood lead concentration (PbB) of 1.7 mumol/l (or 35 micrograms/100 ml), which is lower than the commonly accepted limit value of 2.9 mumol/l (or 60 micrograms/100 ml) for occupationally lead-exposed persons. There was a better correlation between the cheletable lead excretion and the urinary ALA-excretion (r = 0.45; p less than 0.001) than between PbB and the urinary ALA-excretion (r = 0.26; p greater than 0.05).

Adult↗