PubMed HealthSearch

Biomedical subjects

A A Lawson

Publications and source records attributed to A A Lawson.

At least 19 recordsLinked to original sources

Acetylcholinesterase in the human erythron. II. Biochemical assay.

Acetylcholinesterase (AChE) is an integral erythrocyte membrane protein. A role for the enzyme in the developing human erythron is being explored. Assays of AchE by the standard Ellman technique overestimate the amount of enzyme by failing to account for the contribution of hemoglobin to the optical density of the reaction mixture. Furthermore, reliance on substrate selection alone for specificity is unsatisfactory. Incorporation of inhibitors of "true" AchE and of pseudocholinesterase confer greater ability to distinguish one enzyme from the other. In our experience, the inhibitor constant (Kl) for edrophonium, which is highly specific for AChE, is approximately 5 x 10(-5) M against adult human erythrocytes that contain significantly more total cholinesterase activity than do erythrocytes from umbilical cord blood. This consists of both "true" and "pseudo" enzyme, the former predominating and accounting for 0.75-1.65 (mean 1.02, median 0.87) femtomoles of substrate hydrolysed per min per cell in adult blood, with values of 0.15-1.04 (mean 0.71, median 0.73) obtained on cord blood. Moreover, the enzyme activity in neonatal erythrocytes has a rather different inhibitor profile from that of adult cells. AChE was also demonstrated in fresh (ALL) and cultured (K562 and HL60) human leukemic cells, as well as in primitive granulocyte-macrophage and erythroid cells cloned from normal human bone marrow. In the erythroid colonies the enzyme activity was 0-3.76 (mean 1.20, median 0.76) femtomoles per min per cell, apparently the first successful measurement of AChE in such cells.

Acetylcholinesterase

Trends in analgesic self-poisoning in West-Fife, 1971-1985.

All admissions for analgesic self-poisoning to a district poisons unit over a 15-year period have been reviewed. During this time overdose with analgesic drugs increased to represent almost half of all admissions for self-poisoning. The types of analgesics taken in overdose also changed significantly during the period of this review. Aspirin and Distalgesic poisoning declined in incidence and more cases of self-poisoning by paracetamol and non-steroidal anti-inflammatory agents were seen. The impact of these changes on the medical management and outcome of deliberate self-poisoning is analysed. The reasons behind the trends described in this paper are assessed and their implications for future prevention and treatment are discussed.

Acetaminophen

Association between liberalization of Scotland's liquor licensing laws and admissions for self poisoning in West Fife.

Data were collected prospectively on 2868 consecutive patients admitted for self poisoning between 1971 and 1982. Analysis showed a dramatic increase in the frequency of alcohol taken in association with self poisoning, in both sexes, after the liberalization of Scotland's liquor licensing laws. This increase, however, did not appear to affect the severity of overdoses or the outcome. Total admission rates for self poisoning increased with relaxation of the liquor licensing laws, and since overdoses associated with alcohol tend to occur at night these impose considerable strain on casualty departments and acute admitting units.

Alcohol Drinking

Parenteral chlorpromazine and frusemide: safe and effective treatment for hypertensive emergencies.

Hypertensive emergencies present a difficult problem of management. Although many treatment regimens have been described over the years, their application has presented problems of adverse effects and all have required detailed and intensive supervision of patients. After favourable results obtained in a preliminary study using a combination of parenteral chlorpromazine and frusemide, a 5-year prospective study was conducted using this treatment to produce rapid reduction in blood pressure in patients with acute onset severe hypertension (blood pressure greater than 225/130 mmHg). The patients involved covered a wide range from 22 to 74 years (mean 47 years) and, on subsequent or previous investigation, were all considered to have essential hypertension. Twenty-seven patients were treated successfully with a single administration of the regimen. Two women required a second treatment before adequate control of blood pressure was achieved and 1 man died of extensive dissecting abdominal aortic aneurysm before the effects of the therapy could be fully assessed. The reduction in blood pressure was gradual but progressive over 4 hours and the pattern of response was uniform. No significant adverse effects related to the treatment were found. Only basic measurement of pulse and blood pressure was considered necessary and so this regimen of therapy is suitable for general use even when sophisticated monitoring facilities are not available and staff levels are limited.

Adult

Comparison of sustained-release clonidine and long-acting propranolol in the treatment of hypertension.

A double-blind crossover trial was undertaken to compare the efficacy of sustained-release clonidine and long-acting propranolol in the treatment of 20 patients (8 males and 12 females) with sustained hypertension. Each patient was stabilized with metoprolol with or without diuretic therapy prior to admission to the trial. Long-acting propranolol in a once daily dosage of 160 mg proved to be effective over a 6-week period of treatment with no significant side-effects. Sustained-release clonidine in a single daily dosage of 0.25 mg was also effective over a similar period, but side-effects were more common. Although none were serious, they were sufficiently troublesome to result in 5 patients withdrawing from the trial. Despite this, sustained-release clonidine was considered a suitable drug for the treatment of hypertensive patients in whom beta-blockade is unsuitable.

Adult

Medically serious self-poisoning in West Fife, 1970-1979.

Two thousand two hundred and four patients with acute poisoning admitted between 1970 and 1979 to an acute District Medical Unit were reviewed with special regard to the serious medical consequences of overdosage. The incidence of barbiturate and methaqualone poisonings declined but benzodiazepines, tricyclic antidepressants, and dextroproproxyphene were more commonly taken. As a result, there was no overall change in the proportion of patients admitted unconscious or requiring respiratory support. The dangers of dextropropoxyphene poisoning have become increasingly apparent, and poisoning with paracetamol has become as frequent as salicylate poisoning. In view of these changing trends, measures to limit the morbidity and mortality from self-poisoning are suggested.

Adult

Distalgesic poisoning--cause for concern.

A review of all dextropropoxyphene poisoning episodes in a stable representative population during the past 10 years showed that Distalgesic accounts for most overdoses, and it has become an increasingly popular component of self-poisoning coktails. Sudden respiratory depression due to dextopropoxyphene potentiated by other common ingested agents is the main danger, and at least one-third of patients take a potentially lethal dose (20 tablets of Distalgesic and alcohol or benzodiazepine). Naloxone is an effective antagonist but, because of the rapidity of deterioration, 40% of patients sustain irreversible cerebral damage before reaching resuscitation facilities. Consequently Distalgesic has become the ingested agent principally responsible for self-poisoning deaths over the age of 12 years. This rise to prominence has paralleled a pronounced increase in prescriptions for the drug. The reason for the increased rise in selfpoisoning remains elusive. As effective treatment of the cause is not possible the only way to mitigate its serious consequences is prompt treatment and restrictions on the availability of the drug. No analgesics are devoid of danger in overdose, but in dextropropoxyphene the evidence suggests that its dangers outweigh its analgesic properties.

Acetaminophen

Psychiatric aspects of acute poisoning with tricyclic and related antidepressants--a ten-year review.

The incidence of acute self-poisoning with tricyclic and related antidepressant drugs has increased in recent years so that now approximately 20 per cent of all acute overdoses in patients above the age of 12 are due to this cause. We report the results of a ten-year review of the psychiatric aspects associated with this poisoning in 316 consecutive patients admitted to a District General Hospital. Fifty-four per cent of these patients had sought medical advice in the period immediately prior to the overdosage. The final psychiatric diagnosis following the poisoning is related to the events previously and an attempt is made to judge how appropriate was the original treatment with antidepressant drugs. The important opportunities for prevention of this poisoning are discussed and suggestions made.

Adolescent

Poisoning with tricyclic and related antidepressants--a ten-year review.

Self-poisoning with tricyclic and related anti-depressant drugs has increased in frequency over the last few years so that, at present, some 20 per cent of patients admitted to hospital following self-poisoning have ingested a drug of this group, either alone or, more commonly, in association with alcohol, a benzodiazepine and/or other drugs. We present the results of a retrospective analysis of 316 admissions to a general medical hospital dealing with patients over 12 years, following self-poisoning with tricylic or related drugs. Although serious toxic effects may sometimes occur, their frequency has probably been over-estimated, at least in older children and adults; in this series the incidence of significant hypotension was 13 per cent, grand mal convulsions 4 per cent, respiratory depression to the degree of requiring mechanical ventilation 2 per cent and severe cardiac arrhythmias or conduction disturbances 1.5 per cent. It is suggested that routine 'prophylactic' treatment against convulsions and cardiac arrhythmias, advocated by some previous authors, is unnecessary and potentially dangerous; indeed, even the establishment of an intravenous infusion may put an extra strain on a depressed myocardium. In this series, supportive treatment alone was sufficient for the majority of patients (81.6 per cent) and additional treatment was given only in the presence of some specific indication. Using such conservative measures, the mortality rate in the 10-year study was only 0.6 per cent. Medical efforts in the future, it is suggested, would be more appropriately directed towards preventing unnecessary prescribing of these drugs for trivial mental upset, rather than the development of new drugs of this type or other 'prophylactic' measures, designed to prevent relatively rare toxic effects.

Adult