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Biomedical subjects

D Gompertz

Publications and source records attributed to D Gompertz.

At least 19 recordsLinked to original sources
PubMed1990

Evidence that a beta-N-glucuronide of 4,4'-methylenebis (2-chloroaniline) (MbOCA) is a major urinary metabolite in man: implications for biological monitoring.

Urine samples from workers exposed to 4,4'-methylenebis (2-chloroaniline) (MbOCA) contain a labile metabolite(s) that, on hydrolysis, yields the parent compound at concentrations two to three times those of free MbOCA. Evidence has now been obtained that the major labile metabolite is an N-glucuronide of MbOCA. The N-glucuronide of MbOCA was synthesised chemically, characterised by thermospray mass spectrometry, and found to have a pseudomolecular (M + 1) ion at m/z 443/445. MbOCA and [14C] uridine diphosphoglucuronic acid [( 14C]UDPGA) were incubated with liver microsomes from rats induced with polychlorinated biphenyls. The stoichiometry of the reaction product was about 1:1 (MbOCA:UDPGA). This product, the chemically synthesised glucuronide, and the labile urinary metabolite had identical chromatographic and hydrolytic (heat and beta-glucuronidase) properties. These studies show that the major labile conjugate of MbOCA in the urine of workers exposed to this compound is probably the mono N-glucuronide. In view of the lability of this compound and the fact that its concentration in urine is two to three times that of free MbOCA, it is essential that any strategy for the biological monitoring of exposed workers takes into account the N-glucuronide.

Benzhydryl Compounds↗
PubMed1988

Interactions of m-xylene and aspirin metabolism in man.

In a series of experiments to investigate interactions between industrial solvents and common medications the interaction between m-xylene and aspirin was studied. As both these substances are metabolised and excreted as glycine conjugates there would possibly be competition for this conjugation pathway. Five male volunteers were exposed on separate occasions to m-xylene by inhalation (100 ppm), aspirin (1500 mg) by mouth, and m-xylene and aspirin together under controlled conditions in an exposure chamber. Urine and blood samples were collected and analysed for m-xylene, aspirin, and their metabolites. The amounts of the major glycine conjugates produced from m-xylene (m-methylhippuric acid) and aspirin (salicyluric acid) were significantly reduced by about 50% when m-xylene and aspirin were coadministered. There appears to be a mutual inhibition on the formation of the respective glycine conjugates. It is suggested that the inhibition is due to competition for either the enzymes, acyl-CoA synthetase, or glycine N-acylase. These findings have implications in the biological monitoring of workers exposed to m-xylene.

Adult↗
PubMed1987

Behavioral changes during exposure to 1,1,1-trichloroethane: time-course and relationship to blood solvent levels.

We report the results of an exposure chamber study in which volunteers were exposed to 0, 950 mg.m-3 (175 ppm) and 1,990 mg.m-3 (350 ppm) of 1,1,1-trichloroethane for 3.5 hours. The time-course of the behavioral changes and the relationship to blood concentrations of 1,1,1-trichloroethane were investigated. A pattern of performance deficits consistent with earlier work was found for some of the tests of psychomotor performance. The time-course of these appeared to be rapid, occurring in some cases within 20 minutes of exposure. For those tasks shown to be sensitive to 1,1,1-trichloroethane exposure, the development of performance changes followed the time-course of blood solvent levels. Two behavioral tests not previously used in this type of work were also employed. One was concerned with the distractability of attention and concentration (the Stroop test), and the other was concerned with analysing grammatical statements (the syntactic reasoning test). Different effects were found. In the Stroop test, enhanced performance was observed following exposure; however, the syntactic reasoning test was found to be resistant to solvent effects. Measures of short-term subjective well-being were not affected by exposure. It is suggested that the observations of time-course effects in performance and their relationship to change in blood solvent levels have implications for psychological test selection and for study designs for examining field exposure.

Analysis of Variance↗
PubMed1987

Clinical and immunological investigations of respiratory disease in workers using reactive dyes.

A questionnaire survey of over 400 workers handling reactive dyes showed that over 15% had work related respiratory or nasal symptoms. Forty nine employees with symptoms were referred to chest clinics for detailed assessment. It was considered that in 19 the symptoms could be attributed to an irritant response to a variety of chemicals, including hydrochloric acid vapour, sulphur dioxide, and reactive dyes. Symptoms in 24 were attributed to an allergic reaction to a specific agent; in most (21) to one or more reactive dyes. Two patterns of allergic lower respiratory symptoms were identified; an immediate response of short duration and a longer lasting response, usually of several hours, sometimes accompanied by nocturnal asthma. A radioallergosorbent test (RAST) screen containing the most commonly used reactive dyes was used to detect specific IgE. Allergic symptoms to reactive dyes were strongly associated with specific IgE (17/21 employees) and atopy (18/21). Irritant symptoms were also associated with atopy (13/19) but only weakly associated with specific IgE (7/19).

Coloring Agents↗
PubMed1983

Renal dysfunction in cadmium smelters: relation to in-vivo liver and kidney cadmium concentrations.

Biochemical indicators of renal dysfunction have been compared with liver and kidney cadmium levels measured by neutron activation analysis in a group of 37 cadmium smelters. Higher than normal concentrations of cadmium in the liver reflect past exposure; they were associated with evidence of renal dysfunction in workers exposed to cadmium for more than 10 years. A small group of 6 workers exposed to cadmium for only a short time (mean = 4.6 years) had high hepatic cadmium concentrations but normal renal function. Longitudinal studies are required to establish the natural history of renal dysfunction following cadmium accumulation in industrial workers.

Cadmium↗
PubMed1983

Urinary mutagenicity assays: a problem arising from the presence of histidine associated growth factors in XAD-2 prepared urine concentrates, with particular relevance to assays carried out using the bacterial fluctuation test.

The appearance of mutagenic activity in urine samples from a group of nurses and from unexposed individuals has been investigated using the bacterial fluctuation test. Apparent mutagenic activity was seen in samples from all subjects and did not appear to be related to any specific occupational or environmental exposure. This activity seems to be related to the presence of histidine or histidine-related auxotrophic growth factors in the urine concentrates, not completely removed by the recommended XAD-2 column procedure. It is suggested that the reliance on XAD-2 columns for the removal of histidine may produce spurious results when using this assay to screen populations for exposure to mutagenic chemicals.

Animals↗
PubMed1983

Effect of alcohol on the kinetics of mandelic acid excretion in volunteers exposed to styrene vapour.

The effect of a dose of alcohol on the kinetics of mandelic acid excretion in four volunteers exposed to 220 mg/m3 styrene has been investigated under controlled exposure chamber conditions. Ethanol inhibited the excretion of mandelic acid, so that the peak excretion was delayed from the end of the exposure period until three hours afterwards. One hour after administration of ethanol blood mandelic acid concentrations were 56% of the levels found during the alcohol-free control exposure, and this was paralleled by a 15-fold rise in phenylethane 1,2 diol, the metabolic precursor of mandelic acid. It is suggested that the inhibition of the oxidation of this diol is related to the change in NAD +/NADH ratio produced by ethanol metabolism. The implications of this ethanol effect on the interpretation of urinary mandelic acid excretion when monitoring workers exposed to styrene are discussed.

Adult↗
PubMed1980

[Prognosis of congenital methylmalonic aciduria. Correlations between tolerance to proteins, response to vitamin B12 and enzymatic defect (author's transl)].

In 14 patients with methylmalonic acidemia we studied the correlations between clinical severity (considered in terms of survival and number of acute episodes), daily tolerance to proteins (amounts of leucine, valine, methionine, threonine compatible with good health and a methylmalonic acid excretion below 4 mmol/24h), the in vivo response to vitamin B12 and the nature of the enzymatic defect. This study showed that 2 groups of patients with congenital methylmalonic acidemia may be delineated with respect to prognosis. In patients with complete methylmalonyl CoA mutase deficiency, unresponsive to vitamin B12 in vitro and in vivo, the disease begins most often in the neonatal period and evolution is severe, with frequent acute episodes. Their tolerance to precursor aminoacids is similar to the minimal need (10-15 moles i.e. a total proteic intake of 6-9 g/24 h). None of the 8 patients of this group survived for more than 3 years. Conversely, in the second group (patients with normal in vitro MMCoA mutase activity in the presence of vitamin B12 in excess) the disease begins later, evolution is less severe and tolerance to protein intake is normal or subnormal. However, in this group, in vivo response to vitamin B12 is not constant.

Amino Acid Metabolism, Inborn Errors↗
PubMed1979

The time course of mandelic and phenylglyoxylic acid excretion in workers exposed to styrene under model conditions.

Urinary excretion of mandelic and phenylglyoxylic acids by two technicians building glass-reinforced plastic boats has been measured over a 7-day period. Peak excretion of both metabolites occurred several hours after the end of exposure. There was little relationship between urinary mandelic acid concentrations measured at the end of shift and the maximum excretion observed in samples collected after this time. It is suggested that sampling strategies devised to monitor workers exposed to styrene should reflect maximum excretion rates of urinary mandelic acid.

Environmental Exposure↗
PubMed1978

A protein-binding assay for measurement of biotin in physiological fluids.

A sensitive and convenient protein-binding assay for biotin in physiological fluids is described. The method is based upon the binding of an iodinated biotin conjugate by avidin followed by separation of bound and free conjugate by charcoal absorption. Adult plasma biotin levels averaged 1.26 pmol/ml, a value comparable to that determined by microbiological assays for biotin.

Adult↗
PubMed1978

The variability of metabolite excretion in propionicacidaemia.

Random urine samples from eight patients with propionicacidaemia were analyzed by gas chromatography and mass spectrometry in order to see if a consistent metabolite pattern with a high diagnostic value could be found. However, wide variations were observed. The presence of 3-hydroxypropionate and/or methylcitrate were considered to be diagnostic of propionyl-CoA carboxylase deficiency. In addition, samples from ketotic periods frequently contained 3-hydroxy-n-valerate and 3-oxo-n-valerate.

Amino Acid Metabolism, Inborn Errors↗
PubMed1977

Isovaleric acidaemia in two South African children.

Two siblings who were repeatedly admitted to hospital with acute episodes of vomiting, dehydration and coma were found to be suffering from isovaleric acidaemia. This condition is a rare inherited abnormality of leucine metabolism, which is frequently fatal in the early weeks of life and leads to mental retardation in a high proportion of those who survive early attacts. However, both our patients were of normal intelligence. The clinical presentation, biochemical defect, diagnosis and suggested therapies are reviewed.

Acute Disease↗
PubMed1977

Identification of urinary metabolites of sodium dipropylacetate in man; potential sources of interference in organic acid screening procedures.

Organic acid screening of urine samples from two children with neurological disease demonstrated the presence of two unknown metabolites. The children were receiving an antiepileptic drug, sodium dipropylacetate. The major abnormal compound has been shown by gas chromatography-mass spectrometry to be 3-oxodipropylacetic acid, a previously unidentified metabolite of dipropylacetate in man, while the minor metabolite was indentified as 2-(n-propyl)-glutaric acid.

Acids↗
PubMed1976

The encephalopathic action of five-carbon-atom fatty acids in the rabbit.

1. Five-carbon-atom organic acids (C-5 acids) have been administered intravenously to rabbits with ventriculocisternal perfusion and continuous electroencephalographic recording (EEG). The concentration of the acids in the cerebrospinal fluid (CSF) perfusate have been compared with changes in integrated low-frequency activity in the EEG. 2. The C-5 acids investigated were those accumulating in inborn errors of metabolism, i.e. isovaleric acid, beta-methylcrotonic acid, tiglic acid and alpha-keto- and alpha-hydroxy-isovaleric acid. There activity was compared with that of valeric acid. 3. Valeric acid and isovaleric acid produced coma and pronounced increase in slow-wave electrical activity and these changes paralleled the increase in concentration of the acids in the CSF perfusate. 4. The concentration of beta-methylcrotonic acid and tiglic acid in the CSF perfusate reached values comparable with valeric acid and isovaleric acid but showed less encephalopathic activity. An interaction between beta-methylcrotonic acid and isovaleric acid was observed. 5. Although the concentrations of alpha-ketoisovaleric acid and alpha-hydroxyisovaleric acid rose to the lesser extent in the CSF perfusate, changes in rousability of the animal and in the EEG recording were demonstrated. 6. It is concluded that all the C-5 acids tested have encephalopathic activity although this is lessened by the presence of either a double bond or an oxygenated functional group.

Animals↗