Chemical hazards in the home and workplace.
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Biomedical subjects
Publications and source records attributed to R Goulding.
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Between May 1976 and August 1977 samples of human body fat were taken during routine necropsies in the United Kingdom on 236 subjects aged over 5 years and four infants aged under 4 months. Comparison with results from earlier studies showed a further decline in residues of pp'-dichlorodiphenyltrichloroethane (pp'-DDT) and dieldrin (HEOD) and increased amounts of hexachlorobenzene residues; concentrations of other compounds were similar to those observed in the studies carried out in 1963-4, 1965-7, and 1969-71. Comparison of the data with those from other countries, showed that the concentrations of organochlorine pesticide residues and polychlorobiphenyls in human fat samples from residents of the United Kingdom remain among the lowest in Europe and, indeed, the world.
Hemodialysis or sorbent hemoperfusion has been used in the management of clinical overdose of salicylates or acetaminophen. Hemodialysis offers considerable benefit in severe salicylate poisoning and is preferred to hemoperfusion or peritoneal dialysis, since it more rapidly corrects acid-base and electrolyte abnormalities than does hemoperfusion, and since it is clearly more efficient than is peritoneal dialysis for the removal of salicylates. Charcoal hemoperfusion in animal studies and hemodialysis in man have been shown to accelerate acetaminophen elimination from the body. Hemodialysis and hemoperfusion are of questionable benefit in clinical acetaminophen overdose. However, our clinical experience to date with charcoal hemoperfusion in "late" acetaminophen overdose has been associated with a less notable increase in liver enzyme concentrations in comparison with results of retrospective studies of series of patients treated or not treated with sulfhydryl donors.
One hundred thirty-two cases of severe acetaminophen (paracetamol) poisoning were treated with oral methionine. Seven of 96 patients who received the antidote within ten hours of ingestion of the overdose had severe liver damage (aspartate transaminase level, greater than 1,000 IU/L), but none of these patients died. Thirty-six patients received methionine between ten and 24 hours of ingestion; severe liver damage occurred in 47%, and two patients died. The treatment protocol for oral methionine is simple, and therapy is complete within 12 hours as compared with three days for oral acetylcysteine and 20 hours for intravenous acetylcysteine. Side effects from methionine were unimportant. Oral methionine is as effective as acetylcysteine in preventing severe liver damage and death after acetaminophen overdose. However, as with acetylcysteine, it must be given within ten hours of ingestion to be effective.
The mortality from analgesic poisoning in England and Wales has risen markedly during the last five years, but only a small increase in mortality from acetaminophen poisoning has been seen in the same period. Two separate epidemiologic studies of acetaminophen-overdose patients were undertaken during the two years from 1977 to 1978. Eighty-five percent of 1,644 patients and 95% of 341 patients arrived at the hospital within 12 hours of ingestion of an acetaminophen overdose. Although most patients who ingested hepatotoxic doses of acetaminophen were asymptomatic--347 (66%) of 667 and 26 (51%) of 51 patients--the absence of symptoms did not adversely affect the time of their arrival at the hospital.
1 Seven patients who presented to hospital later than 10 hours following an overdose of paracetamol were treated by charcoal haemoperfusion. 2 In all cases there was a rapid fall in the plasma paracetamol concentrations, although the total amounts of drug removed varied from 364.5 mg to 6699 mg. 3 One patient developed fulminant hepatic failure and died; the remainder recovered, sustaining only mild hepatic damage (maximum AST less than 1000 iu1(-1)). 4 Charcoal haemoperfusion may be effective in mitigating the severity of liver injury in those patients who are not eligible to receive specific antidotal therapy.
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Fifteen patients who were severely poisoned with either hypnotic drugs or salicylate were treated by charcoal haemoperfusion. The device contained 100g of activated charcoal immobilised by fixation to a polyester film. Two patients showed no response and eventually died. The remainder showed marked lightening of coma and recovered uneventfully. Complications of platelet loss and, in one patient, fibrinolysis were observed, but these had no serious consequences. No significant biochemical disturbances occurred with the exception of one patient who presented with hypocalcaemia and required intravenous calcium throughout the treatment. Drug clearance values were comparable with those obtained with columns containing 300 g of acrylic polymer coated charcoal.
Paracetamol is an analgesic and antipyretic agent which was first marketed for use as a drug in the U.K. in 1956. It has since become popular with the medical profession and the general public as an alternative to aspirin.
A haemoperfusion column containing activated charcoal coated with cellulose acetate was used to treat 7 patients with barbiturate or ethchlorvynol poisoning. Six of the patients showed marked lightening of coma and all showed a significant fall in plasma drug concentration. Plasma drug clearance and platelet loss were similar to those reported for other coated charcoal columns. Cellulose acetate-coated charcoal haemoperfusion may reduce the period of coma in severe poisoning with barbiturates and other hypnotic drugs and thus the morbidity and mortality.
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Although opinions differ to some extent there is increasing belief in the value of monitoring plasma levels for effective therapy with neuropsychiatric drugs, especially with anticonvulsants. Monitoring should not be on a comprehensive and routine basis, but should be selective and discriminating. In these circumstances the expenditure incurred on the laboratory operations involved might work out for Britain at about pounds 5 million per year. This figure should be compared to a total annual expenditure from the prescribing of neuropsychiatric medication amounting to an estimated pounds 40 million per year. The benefits thus achieved in patient care, together with the possible economies in prescribing, could well merit this monitoring exercise. In terms of personnel and administration, the laboratory facilities could be organized on a regional, or on a district general hospital, basis.
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