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Biomedical subjects

H K Wilson

Publications and source records attributed to H K Wilson.

At least 37 records · Page 2Linked to original sources
PubMed1990

Bile acids and the increased risk of colorectal tumours after truncal vagotomy.

An association between colorectal cancer and previous peptic ulcer surgery is reported. In a prospective screening study, 100 asymptomatic patients (80 men and 20 women) who had undergone truncal vagotomy at least 10 years previously were investigated by barium enema, colonoscopy and gallbladder ultrasonography. Control data were obtained from forensic autopsy subjects. The incidence of neoplasms greater than or equal to 1.0 cm in the vagotomized group was 14 per cent (11 adenomas, 3 carcinomas) and 3 per cent in controls (P = 0.01). Duodenal bile obtained at endoscopy from 21 vagotomized patients with normal gallbladders and from 21 control patients undergoing endoscopy was analysed by high performance liquid chromatography. The mean percentage of cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA) and lithocholic (LCA) acids in the bile of vagotomized patients was 32.3, 45.6, 20.7 and 1.4 per cent respectively compared with 45.3, 36.2, 17.9 and 0.7 per cent respectively in controls. The increased proportions of CDCA and LCA and decreased proportions of CA in the duodenal bile of vagotomized patients were significant (P less than 0.001; P = 0.02; P = 0.007). Abnormalities in bile acid metabolism may help to explain the increased risk of colorectal neoplasia 10 years after truncal vagotomy.

Bile Acids and Salts↗
PubMed1990

Human inhalation pharmacokinetics of 1,1,2-trichloro-1,2,2-trifluoroethane (FC113).

Seven male volunteers were exposed to atmospheric concentrations of either 1980, 4100 or 7630 mg m-3 1,1,2-trichloro-1,2,2-trifluoroethane (FC113) for 4 h. Blood and expired air samples were collected during the exposure period and for several days subsequently and analysed for FC113. Blood and breath concentrations of FC113 were related to the administered dose with some variation between individuals. The low blood/breath ratios measured are consistent with the low solubility of FC113 in blood. The absorption and elimination of FC113 can be described by a three-compartment model and the average half-lives of elimination of FC113 in breath were 0.22, 2.3 and 29 h. A pulmonary retention during the exposure period of 14% was measured but only 2.6 to 4.3% of the dose was recovered unchanged in breath after the exposure period, suggesting that FC113 could be metabolised following inhalation exposure. It is concluded that a practical method for biological monitoring during occupational exposure would be to measure end-tidal breath concentrations of FC113 in samples taken the morning after exposure. The predictive value of such a measurement can be improved if the results are normalised to the body fat content of individual workers which can be estimated from height and weight measurements.

Administration, Inhalation↗
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↗
PubMed1990

The stereoselectivity of 1,2-phenylethanediol and mandelic acid metabolism and disposition in the rat.

1. The steps involved in determining the chirality of the mandelic acid excreted by rats after administration of ethylbenzene and styrene were investigated by studying the fate of racemic, (R)- and (s)1,2-phenylethanediol, a precursor of mandelic acid. These investigations indicate the occurrence of two alternative routes of metabolism for 1,2-phenylethanediol, one involving retention of configuration and the other resulting in the loss of the chiral centre. 2. The stereoselectivity of the disposition of mandelic acid was investigated; rats were dosed with mandelic acid either as the racemate or as the individual enantiomers, G.1.c.-mass spectrometry and h.p.l.c. were used to determine the enantiomers of mandelic acid. 3. There were at least two routes by which mandelic acid could be metabolized and/or excreted; there is a stereoselective pathway in rat for (s)-mandelic acid, which gives rise to phenylglyoxylic acid. 4. The chiral inversion of (s)-mandelic acid to (R)-mandelic acid is reported; although this has been observed in bacteria it has not previously been observed in mammals. 5. The extent to which mandelic acid is metabolized to phenylglyoxylic acid is dependent on the enantiomeric composition of the mandelic acid administered. There is no evidence to indicate significant ketone-alcohol conversion, that is phenylglyoxylic acid is not significantly reduced to mandelic acid in vivo.

Animals↗
PubMed1989

The metabolism of ethylbenzene and styrene to mandelic acid: stereochemical considerations.

1. The stereochemistry of mandelic acid, produced as a major urinary metabolite of ethylbenzene and styrene in rat and man has been investigated. Although these solvents are both achiral they are metabolized to chiral metabolites, via a series of chiral intermediates. 2. Analytical methods (g.l.c.-mass spectrometry, h.p.l.c. and 19F-n.m.r.) have been developed for the determination of the enantiomeric composition of mandelic acid in urine. 3. These methods have been applied to the study of the metabolic stereochemistry of ethylbenzene and styrene in rats dosed orally (100 mg/kg body weight) and in human volunteers exposed to atmospheres containing these solvents at the upper limits prescribed for workplaces by the UK Health and Safety Executive (100 ppm in air). 4. Results show that whereas only the R-enantiomer of mandelic acid was excreted after ethylbenzene exposure, the mandelic acid formed from styrene was essentially racemic. In three workers occupationally exposed to styrene, ratios of R to S isomers of 1.16, 1.27 and 1.14 were found. A synthetic R/S mixture of mandelic acid had an R/S ratio of 1.03. 5. The implications of these findings for the biological monitoring of workers occupationally exposed to stryrene and/or ethylbenzene are discussed.

Animals↗
PubMed1989

Cholecystectomy and the development of colorectal neoplasia: a prospective study.

One hundred asymptomatic patients over 60 years of age who had cholecystectomy carried out at least 10 years earlier underwent double contrast barium enema and sigmoidoscopy. The incidence of colorectal adenomas and carcinomas was compared with age and sex matched controls undergoing routine post mortems. In the post-cholecystectomy group 12% had tumours (8 adenomas greater than 1 cm in diameter, 4 carcinomas). In the control group 3% had tumours (3 adenomas); P = 0.02. This study confirms that patients with a history of cholecystectomy have an increased risk of developing colorectal adenomas and carcinomas.

Adenoma↗
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↗
PubMed1988

Biological monitoring of workers exposed to benzene in the coke oven industry.

Workers in the coke oven industry are potentially exposed to low concentrations of benzene. There is a need to establish a well validated biological monitoring procedure for low level benzene exposure. The use of breath and blood benzene and urinary phenol has been explored in conjunction with personal monitoring data. At exposures of about 1 ppm benzene, urinary phenol is of no value as an indicator of uptake/exposure. Benzene in blood was measured by head space gas chromatography but the concentrations were only just above the detection limit. The determination of breath benzene collected before the next shift is non-specific in the case of smokers. The most useful monitor at low concentrations appears to be breath benzene measured at the end-of-shift.

Adult↗
PubMed1988

Plasma gamma-hexachlorocyclohexane concentrations in forestry workers exposed to lindane.

Plasma gamma-hexachlorocyclohexane (gamma-HCH) and three urinary trichlorophenols were measured in forestry workers who were engaged in planting seedlings treated with gamma-HCH. These two procedures were assessed as potential biological monitoring methods and the data were compared with reported clinical symptoms. The measurement of plasma gamma-HCH was considered to be a feasible and valid monitoring method for use in routine practice and is a useful indicator of gamma-HCH absorption. The data were used to illustrate the need to be vigilant about personal hygiene and the efficacy of protective clothing. Plasma gamma-HCH concentrations above 70 nmol/l were measured in two workers which coincided with persistent non-specific clinical symptoms. Trichlorophenols were identified in urine but the extensive and variable metabolism of gamma-HCH makes this approach less suitable for biological monitoring.

Agriculture↗
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↗
PubMed1986

Assessment of occupational exposure to 4,4'-diaminodiphenylmethane (methylene dianiline) by gas chromatography-mass spectrometry analysis of urine.

A new specific and sensitive method has been used to monitor workers from five different factories where 4,4'-diaminodiphenylmethane (methylene dianiline) (DDM) was being used. The isolation and identification of an N-acetyl conjugate of DDM, a major metabolite of DDM found in human urine, is reported for the first time. The use of this biological monitoring method will allow the assessment of the absorption of DDM and help in monitoring improvements in work practices, particularly where exposure may occur through pathways other than inhalation.

Acetanilides↗
PubMed1986

Prolonged action of regular insulin in diabetic patients: lack of relationship to circulating insulin antibodies.

We previously reported that in insulin-treated diabetic subjects the time course of action of regular insulin injected sc is different from that reported in standard textbooks. The present studies evaluated the role of insulin antibodies (Abs) in the altered pharmacokinetics of regular insulin by comparing the time course of insulin action in 10 patients receiving chronic insulin therapy and having insulin Abs with that in 15 previously untreated patients without detectable Abs. After an overnight fast, the patients were given an infusion of 5% dextrose in water at 100 ml/h. Regular insulin (15 U) was then injected sc in the deltoid region of the arm. The onset of action of sc insulin, as indicated by a 10% fall in serum glucose, was similar in both patient groups [1.9 +/- 0.1 (+/- SEM) hour in Ab-negative and 1.8 +/- 0.1 h in Ab-positive patients]. The peak effect of insulin action, as determined by the nadir of serum glucose, was 4.6 +/- 0.2 h in the previously untreated patients, not significantly different from the value in the diabetic patients with insulin Abs (5.2 +/- 0.4 h). The duration of action of insulin was also similar in both groups (14.7 +/- 0.7 vs. 14.4 +/- 1.0 h). No significant correlations were found between insulin Ab levels and any of these 3 parameters of insulin action. However, the peak effect and total duration of insulin action were significantly correlated with the baseline serum glucose levels. A possible role of insulin Abs was evaluated in these patients by repeating the studies over a 2-year period. During this time, the previously untreated patients were treated with highly purified pork insulin, to which they developed low titers of insulin Abs. The diabetic patients who had been chronically treated with insulin were changed from less purified insulin to highly purified pork insulin, and all had a significant reduction in their Ab titers. No changes in insulin pharmacokinetics were found in either group. These studies demonstrate that the prolonged action of sc injected regular insulin in diabetic patients is not related to the effect of circulating insulin Abs.

Adult↗
PubMed1986

Breath analysis. Physiological basis and sampling techniques.

This paper examines the physiological basis for breath analysis and draws attention to the factors which may affect the blood:breath ratio. A review of recent breath analysis techniques is presented, and some consideration is given to the use of breath analysis in the biological monitoring of workers exposed to solvents.

Breath Tests↗
PubMed1985

Evaluation of occupational exposure to carbon disulphide by blood, exhaled air, and urine analysis.

This paper compares three analytical methods that may be considered for monitoring workers who are exposed to carbon disulphide (CS2). An estimate of the uptake of CS2 was assessed by the measurement of "bound" CS2 in blood, CS2 in expired alveolar air, and 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. The concentration of TTCA in end-of-shift urine samples was related to exposure and appears to be a good measure of uptake of CS2.

Adult↗