bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metoprolol α-Hydroxylation Polymorphism in the San Bushmen of Southern Africa
Authors: Sommers De K. , Moncrieff J. , Avenant J. 
Published: December 2008

1 The metabolic oxidation of metoprolol has been studied in a group of 98 San Bushmen. 2 The amounts of metoprolol and α-hydroxy metoprolol excreted in 0-8 h urine collection, after dosing with 100 mg metoprolol, were measured and the metabolic ratio (% dose excreted as metoprolol/% dose excreted as α-hydroxy metoprolol) calculated. 3 Frequency distribution and probit plots of the metabolic rate data showed a bimodal distribution with 4.1% of the population exhibiting slow metabolism with an MR > 10. 4 These results are much less than found in Caucasians (8.4%) but very different from the unimodal distribution found for Nigerians. 5 A previous study in the same group of Bushmen had revealed that 18 of 96 subjects were poor or non-metabolizers of debrisoquine to 4-hydroxy debrisoquine, but only one of the poor metoprolol metabolizers was a poor metabolizer of debrisoquine. 6 On the basis of these results, the claim of debrisoquine type of polymorphism for β-adrenoceptor antagonists found in Caucasians cannot be extrapolated to the San Bushmen, and one must query the use of debrisoquine as measure of oxidative status in any group other than Caucasians.
Hyperaluminaemia Associated with Oral Citrate and Aluminium Hydroxide
Authors: Kirschbaum B.B. , Schoolwerth A.C. 
Published: December 2008

1 A hospitalized patient with renal failure receiving oral aluminium hydroxide was found to have a blood aluminium level of 3124 μg/l (116 μmol/l) . 2 The extremely high aluminium concentration was attributed to the concurrent use of an oral citrate solution which converted the aluminium to a more soluble and absorbable form. 3 The combination of oral aluminium and citrate should be avoided in patients with poor renal function.
The UK Blood Lead Monitoring Programme 1984-1987: Results for 1986
Authors: Quinn M.J. , Delves H.T. 
Published: December 2008

The Department of the Environment (DOE) undertook an extensive programme to monitor blood lead concentrations annually over the period 1984 to 1987 in the context of the reduction in the maximum permissible lead content of petrol from 0.4 to 0.15 g/l from 1st January 1986. Blood samples (all venous) were analysed for lead by atomic absorption spectrophotometry (AAS); considerable efforts were made to ensure the validity of the analytical results. In 1986, emissions from petrol driven vehicles effectively fell by 60% and air lead concentrations fell by just over 50%. Against the background of a long-term downward trend in blood lead concentrations of 4-5% per year, there were average falls in blood lead in 1986, compared with 1985, of around 1 μg/100 ml (9-10%) for adults in both 'exposed' and 'control' groups; about 2 μg/100 ml (18%) in traffic police; and about 1.5 μg/100 ml (16%) in children. Levels fell in 1986 in all age groups, in all social classes, and in all categories of smoking and drinking habits, age of dwelling and length of residence. Exposure to lead from a number of sources was being reduced simultaneously; blood lead concentrations probably fell in both 1985 and in 1986 for reasons additional to the reduction in the lead content of petrol. For children, petrol lead appeared to have been made a slightly larger contribution to the body burden than for adults.
Effect of Theophylline and Salbutamol on Hepatic Drug Metabolism
Authors: Døssing M. , Evald T. , Lange P. , Christensen H.R. 
Published: December 2008

Fifteen otherwise healthy asthmatics with reversible airway obstruction were treated with salbutamol (8 mg slow release twice daily) and theophylline (300 mg twice daily). Each drug was administered for 4 weeks in a double-blind randomized crossover trial. Irrespective of which drug was given first, salbutamol increased antipyrine clearance significantly by a factor of 1.10 and 1.15 after 2 and 4 weeks of treatment, respectively. Theophylline did not change antipyrine clearance. There was no correlation between the extent of change in antipyrine clearance during either of the drug treatments and alterations in lung function as assessed by changes in peak flow, forced vital capacity and forced expiratory volume in first second.
Pharmacokinetic Interaction Between Indoramin and Ethanol
Authors: Abrams S.M.L. , Pierce D.M. , Johnston A. , Hedges A. , Franklin R.A. , Turner P. 
Published: December 2008

1 The effect of ethanol consumption (0.5 g/kg) on the pharmacokinetics of the alpha adrenoceptor antagonist indoramin, administered orally (50 mg) or intravenously (0.175 mg/kg) has been investigated in young volunteers. Sedation was also assessed using a visual analogue scale. 2 After oral indoramin administration, ethanol caused increases of 58% (P <0.01) in CPmax , and 25% (P <0.05) in AUC. There was no effect of alcohol on elimination half-life. The combination of ethanol and indoramin was more sedative than indoramin alone. 3 Ethanol did not alter the pharmacokinetics of an intravenous dose of indoramin. However indoramin caused a small but statistically significant increase (26%) in blood ethanol concentrations during the first 1.25 h after dosing. Both indoramin and ethanol caused sedation. 4 The increased bioavailability of oral indoramin in the presence of ethanol may reflect some enhanced absorption, but it is also consistent with inhibition of first-pass metabolism of a flow-limited drug. The clinical implications are discussed.
Use and Abuse of Volatile Substances in Industry
Authors: Parker S.E. 
Published: December 2008

1 Although there are trends towards the use of 'safer' or non-solvent materials, the overall consumption of solvents will probably not change very much over the next few years. Substitution of solvents by 'safer' materials is a complex and difficult process and the rate of change is correspondingly slow. 2 HSE exposure data show that generally industry controls most solvent use quite well. High personal exposures are not widespread and tend to occur in a fairly small number of premises involving 'end user' processes (mixing, spraying, etc). 3 Exposure in industry is generally to mixtures of solvents rather than single substances. The degree to which abuse is a contributory factor in exposure is uncertain, but there is probably greater opportunity for abuse to occur in 'end user' processes. 4 The experience of the author and colleagues in the HSE supports the evidence for the occurrence of volatile substance abuse (particularly of organic solvents) in industry but the extent of the practice is not known. 5 The proposed Control of Substances Hazardous to Health Regulations (COSHH) will bring greater emphasis on the assessment of risks to health in industry, which must include the potential for abuse, together with appropriate training and supervision.
Volatile Substance Abuse: Evaluation and Treatment
Authors: Richardson H. 
Published: December 2008

1 A scheme for the identification and evaluation of volatile substance abusers is outlined which emphasizes the need for medical history, drug history, emotional/behavioural and dependency questionnaires and physical examination. 2 Poor initial evaluation may lead to non-recognition of dependent abusers who may present later with more serious problems. 3 Suggestions for prevention and treatment of chronic abusers are discussed and some advice for parents is outlined.
Rhabdomyolysis and Acute Renal Failure Induced by Paraphenylenediamine
Authors: Averbukh Z. , Modai D. , Leonov Y. , Weissgarten J. , Lewinsohn G. , Fucs L. , Golik A. , Rosenmann E. 
Published: December 2008

1 We present a 40-year-old healthy man who developed a typical clinical picture of rhabdomyolysis following the administration of paraphenylenediamine by a witchdoctor as a pain killer. 2 Two groups of 15 mice were given paraphenylenediamine 70 mg/kg and 35 mg/kg respectively. Biochemical and histological findings of rhabdomyolysis developed in both groups, without kidney damage. 3 Paraphenylenediamine may cause rhabdomyolysis resulting in acute renal failure in humans. In mice, however, it produces rhabdomyolysis, but the kidneys are not affected.
Non-correlation between Debrisoquine and Metoprolol Polymorphisms in the Venda
Authors: Sommers De K. , Moncrieff J. , Avenant J. 
Published: December 2008

1 The metabolic 4-hydroxylation of debrisoquine has been studied in a group of 98 black African villagers in Vendaland. 2 The metabolic α-hydroxylation of metoprolol has been studied in 94 of the same black African villagers. 3 A 4% prevalence of poor oxidative metabolism of debrisoquine and a 7.4% incidence of poor oxidation of metoprolol were found. The 4% result for debrisoquine differs considerably from the 19% found in San Bushmen, 30% in Hong Kong Chinese, 9% in Britains and 0% in Nigerians and Japanese, whilst the 7.4% result for metoprolol compares with 8.4% in Britains but differs from 0% in Nigerians and 4.1% in San Bushmen. 4 None of the poor oxidative metabolizers of debrisoquine were also poor oxidative metabolizers of metoprolol. This is contrary to results in British and Nigerian subjects where defective oxidation of metoprolol co-segrates with that of debrisoquine. 5 No similarities were found between the Venda metabolic ratio (MR) distributions and either extensive or poor MR distributions in Britains or Nigerians.
Monitoring of Patients taking Canthaxanthin and Carotene: An Electroretinographic and Ophthalmological Survey
Authors: Arden G.B. , Oluwole J.O.A. , Polkinghorne P. , Bird A.C. , Barker F.M. , Norris P.G. , Hawk J.L.M. 
Published: December 2008

1 Patients who have taken canthaxanthin and beta-carotene to avert phototoxicity have been monitored by electroretinographic testing. 2 Patients took the compounds only during the summer months, but were monitored for more than 1 year to determine if seasonal changes in the ERG were visible. 3 The characteristic refractile retinal crystals reduced during the winter. 4 The scotopic b-wave amplitude increased during the winter, whether evoked by red or blue flashes. 5 No other ERG parameter altered. 6 Changes noted in 3 and 4 above are reversible. 7 A dose/ERG-amplitude response relationship was established, but no correlation between blood level or total cumulative dose and b-wave amplitude could be found. 8 It is suggested that the Müller cells concentrate canthaxanthin and this is the mechanism which affects the ERG.
Toxicokinetics of Paraquat in Humans
Authors: Houzé P. , Baud F.J. , Mouy R. , Bismuth C. , Bourdon R. , Scherrmann J.M. 
Published: December 2008

1 The toxicokinetics of paraquat were studied in 18 cases of acute human poisoning using a specific radioimmunoassay. Plasma paraquat concentration exhibited a mean distribution half-life ( t½ α) of 5 h and a mean elimination half-life ( t½ β) of 84 h. Cardiovascular collapse supervened early during the course of the intoxication and was associated with the distribution phase. Death related to pulmonary fibrosis occurred late and was associated with the elimination phase. 2 Pharmacokinetic analysis of urine paraquat excretion confirmed the biphasic decline of paraquat. Moreover, renal paraquat and creatinine clearances were not correlated but renal paraquat clearance was never higher than the renal creatinine clearance. 3 Tissue paraquat distribution was ubiquitous with an apparent volume of distribution ranging from 1.2 to 1.6 l/kg. Muscle could represent an important reservoir explaining the long persistence of paraquat in plasma and urine for several weeks or months after poisoning.
High Serum Concentrations of Aflatoxin in Nepal as Measured by Enzyme-Linked Immunosorbent Serum Assay
Authors: Denning D.W. , Sykes J.A. , Wilkinson A.P. , Morgan M.R.A. 
Published: December 2008

1 Sera from 28 Nepalis, both patients and workers in a hospital in Banepa, Nepal were examined for AFB1 by enzyme-linked immunosorbent assay (ELISA). 2 This assay, previously validated using spiked sera, provides a sensitive rapid determination of serum aflatoxin (B1, G1 and Q1). 3 All 28 sera were positive with concentrations from 60 pg ml-1 to 10 ng ml-1 . 4 These results suggest that consumption of aflatoxin in Nepal is high (> 50-800 ng kg -1 d-1). 5 No reports of the degree of contamination of food, human consumption or body fluid concentrations of aflatoxin in Nepal have been previously published. 6 Aflatoxin may contribute to the development of hepatocellular carcinoma, which is probably a common tumour in Nepal.
Management of Methomyl Poisoning
Authors: Martinez-Chuecos J. , Molinero-Somolinos F. , Solé-Violàn J. , Rubio-Sanz R. 
Published: December 2008

Eleven patients who suffered methomyl poisoning were admitted to the intensive care unit. All of them showed cholinergic symptoms similar to that produced by organophosphate insecticides but of lesser intensity. Plasma cholinesterase activity was normal in four patients and moderately lower in the remainder (always above 32%). All of the patients showed miosis and none presented with bradycardia. No complications were detected in the acute stage or on further examination a month later. The treatment applied was: (1) gastric lavage or washing the skin; (2) the administration of activated charcoal; (3) small doses of atropine according to symptoms (average of total dose 4.3 mg). All of the patients recovered within 24-48 h. In conclusion, we can assume that methomyl poisoning does not produce serious complications if moderate surveillance is assumed. Only small doses of atropine are required to counteract symptoms.
Chronic Occupational Lead Exposure and Testicular Endocrine Function
Authors: McGregor A.J. , Mason H.J. 
Published: December 2008

The effects of moderate lead exposure on testicular endocrine function were evaluated in a group of 90 males who were occupationally exposed to inorganic lead. Lead concentrations in blood and bone were measured as indices of short-term and long-term, cumulative exposure, respectively.The results of this study show that the lead exposure levels encountered in the UK at present may result in a subclinical increase in follicle stimulating hormone (FSH), which is related to blood lead levels. This suggests that lead may be causing some subclinical primary damage to the seminiferous tubules in the testes. However, at blood lead levels of less than 47 μg dl-1this effect on serum FSH is not apparent. There was no significant effect on serum testosterone concentrations or the free testosterone index. The mean luteinizing hormone (LH) level in the exposed group was found to be lower than in the control population. However, there appeared a confoundingly significant positive correlation between serum luteinizing hormone levels and the length of occupational lead exposure within the exposed group.
Study on Kidney Function in Female Workers Exposed to Perchlorethylene
Authors: Vyskočil A. , Emminger S. , Tejral J. , Fiala Z. , Ettlerova E. , Cermanová A. 
Published: December 2008

1 Biochemical markers of kidney damage were examined in 16 female workers chronically exposed to tetrachlorethylene (TCE) in five dry-cleaning shops. The results were compared with those obtained in 13 females non-occupationally exposed to organic solvents. 2 The intensity of exposure was monitored by personal environmental monitoring. The time-weighed average exposure to TCE amounted to 157 mg m-3 (range 9-799 mg m-3). A satisfactory agreement was found between the concentration of TCE in ambient air sampled with the charcoal tube method and with a passive dosimeter. 3 The urinary excretion of lysozyme was increased in the exposed group. No difference was found in the urinary excretion of albumin, β2-microglobulin, lactate dehydrogenase, total proteins or glucose. The prevalence of abnormal values of biochemical parameters in the exposed group did not differ from that observed in the control group. No correlation was found between the level of TCE exposure and biochemical parameters. 4 The present study suggests that chronic exposure to TCE does not lead to renal damage.
The Efficacy of DTPA Treatment after Deposition of Thorium Nitrate in the Rat Lung
Authors: Stradling G.N. , Moody J.C. , Gray S.A. , Ellender M. , Hodgson A. 
Published: December 2008

The efficacy of CaDTPA and ZnDTPA, the chelating agents of choice for several actinide elements, have been evaluated after the deposition of thorium in the rat lung in widely different amounts. The results showed that: 1 When the initial mass concentration of thorium simulated human exposure to four times the annual limits on intake for 232Th, the prompt (300 or 1000 μmol kg -1 body weight at 0.02 d) or repeated (30 or 300 μmol kg-1 body weight at 0.02, 0.25, 1,2,3 d) administration of CaDTPA were at best only moderately successful for enhancing the elimination of thorium. By 7 d after exposure, the body contents of thorium were, respectively, about 74%, 65%, 90% and 74% of those present in untreated animals. 2 When the mass concentration simulated 1.7 X 10-3 times the annual limits on intake for 232Th, the efficacy of treatment was not increased appreciably despite the substantial reduction in mass. After the repeated administration of CaDTPA at doses of 30 and 300 μmol kg-1 using the protocol above, the body contents of thorium by 7 d were, respectively, 69% and 51% of those in untreated animals. 3 Under comparable conditions, the efficacy of ZnDTPA was less than CaDTPA. The results suggest that more effective chelating agents are needed for the treatment of workers exposed to water soluble thorium compounds.
Dopamine and Dobutamine Reduce Myocardial d-Propoxyphene Content in Experimentally Intoxicated Rats
Authors: Pedersen C.B. , Strøm J. , Angelo H.R. , Munksgaard A. , Høgskilde S. , Bredgaard Sørensen M. 
Published: December 2008

The effect of sympathomimetic intervention with dopamine or dobutamine on the myocardial uptake of d-propoxyphene was investigated experimentally in rats. The d-propoxyphene (19 mg kg-1 h-1) was continously infused, intravenously, over 45 min. After 20 min of infusion the rats were given either dopamine (12.5 ?g kg-1 min-1 or 25 ?g kg-1 min-1), dobutamine (25 ?g kg-1 min-1 or 45 ?g kg-1min-1) or normal saline (control). Each group consisted of eight rats. The myocardial d-propoxyphene content was significantly lower in the two groups given dopamine and in the group given dobutamine 45 ?g kg-1 min-1 than in the control group (P < 0.05). This finding indicates the benefit of early sympathomimetic intervention with either dopamine or dobutamine in d-propoxyphene intoxication.
Delayed Calcium Channel Blockade with Diltiazem Reduces Paracetamol Hepatotoxicity in Mice
Authors: Deakin Charles D. , Gove Christopher D. , Fagan Elizabeth A. , Tredger J. Michael , Williams Roger 
Published: December 2008

1 Diltiazem (30 mg kg-1body weight, intraperitoneally) given to mice 9 h after paracetamol (450 mg kg-1, orally) reduced liver damage, as judged by plasma aspartate aminotransferase activity (median 186, range 6-602 IU I-1, n = 18 vs 466, range 23-3872 IU I-1in 18 saline-treated controls; P < 0.05) with comparable reductions in mortality (14% vs 33%, respectively; NS).2 Regenerative activity, as judged by mitotic figures in tissue removed at 30 h after paracetamol, was significantly higher in mice treated at 9 h with diltiazem (median 0.83 per high power field vs 0.1 in saline-treated controls; P < 0.05).3 Diltiazem administered earlier or later than 9 h showed reduced efficacy and in some cases potentiated toxicity, as did nifedipine (40 mg kg-1in divided doses up to 9 h).
Radiation Detriment: Its Quantification and Use in Setting Standards
Authors: Clarke R.H. 
Published: December 2008

At the end of 1990 the International Commission on Radiological Protection adopted new recommendations for the control of exposure to ionizing radiation. The main reasons for the revision of existing standards were first, the new estimates of the risks associated with exposure and second, the need to develop a conceptual framework that covered not only occupational exposures but also radon in homes and the consequences of accidents. This paper addresses these issues and shows how the definition of radiation detriment is used to set new standards in a System of Radiological Protection.
Occupational Mercury Vapour Exposure and Testicular, Pituitary and Thyroid Endocrine Function
Authors: McGregor A.J. , Mason H.J. 
Published: December 2008

We have investigated the pituitary-testicular axis in a well-characterized population which was occupationally exposed to mercury vapour. Thyroid stimulating hormone and prolactin were also measured as indices of thyroid and pituitary endocrine function. We found no relation between blood or urine mercury levels or length of occupational exposure with any measurement of endocrine function.A small, but statistically significant negative correlation between serum sex-hormone binding globulin and the duration of occupational exposure to mercury was found. The physiological significance of this result is unclear.
Failure of a 21-Aminosteroid Antioxidant to Ameliorate Cisplatin-Induced Nephrotoxicity
Authors: Holding J.D. , Stell P.M. , Lindup W.E. 
Published: December 2008

1 Lazaroid (U74500A), a 21-aminosteroid antioxidant, was administered to rats at a dose of 10 mg kg-1 in an attempt to reduce the toxicity of cisplatin (5 mg kg -1). 2 No protective effect was apparent under the schedule used and, in contrast to other antioxidants and free-radical scavengers, U74500A offers no potential benefit in cisplatin treatment.
Distribution and Elimination of [2-14C]Amino-3, 8-Dimethylimidazo [4, 5-f] quinoxaline in Mice. Analysis by Whole Animal Autoradiography
Authors: Gooderham N.J. , Soames A. , Rice J.C. , Boobis A.R. , Davies D.S. 
Published: December 2008

1 2-Amino-3,8-dimethylimidazo[4,5- f]quinoxaline (MeIQx) is a potent bacterial pro-mutagen and carcinogen, formed when beef is cooked. In mammals, MeIQx is metabolized and activated by liver enzymes, but induces tumours in both hepatic and extrahepatic tissues. 2 Intravenous administration of [14C]MeIQx and whole animal autoradiography has been employed to examine the diposition of MeIQx. Within 10 min, radiolabel was distributed throughout body tissue. Liver levels of radioactivity rapidly rose and remained elevated in comparison to other tissues, throughout the period of study (4 d). 3 At early time points radioactivity accumulated in the stomach, kidney and salivary glands then later in the intestine. Radioactivity was rapidly eliminated from the majority of tissues although did persist in liver and intestines throughout the duration of the study, probably due to covalently bound material. No radioactivity could be detected in the central nervous system, thus neither MeIQx nor its metabolites cross the blood—brain barrier to any significant extent. 4 The rapid elimination of radioactivity from the tissues is in good agreement with the time course of excretion of MeIQx. Irrespective of the route of administration (i.v., i.p., p.o.), a substantial proportion of the labelled material is excreted within 24 h and is present in both urine and faeces in similar quantities. 5 Thus MeIQx is extensively bioavailable, is distributed throughout body tissue and, although the majority is quickly cleared, some remains bound to liver and intestine.