Sagittal joint kinematics, moments, and powers are predominantly characterized by speed of progression, not age, in normal children.

Twenty-six healthy 7-year-old children were enrolled in a 5-year longitudinal study to examine the importance of age and speed in the characterization of sagittal joint angles, moments, and powers. In 740 gait trials, children walking at self-selected speeds were examined on the basis of age and normalized speed [speed/(height x g)1/2]. The kinematics and kinetics in these children were characterized predominantly by normalized speed of progression and not age. The clinical relevance of these findings is that normalized speed of walking, rather than age, should be considered when comparing normal with pathologic gait.

Normalized speed, not age, characterizes ground reaction force patterns in 5-to 12-year-old children walking at self-selected speeds.

Twenty-six healthy 5-year-old children were enrolled in a 7-year longitudinal study to examine the importance of age and speed in the characterization of ground reaction forces. One thousand forty gait trials of children walking at self-selected speeds were examined on the basis of age and normalized speed [speed/(height x g)(1/2)]. Results, presented as discrete peak and trough values and as continuous trace plots over the stance phase, indicated that there was little change in ground reaction forces with age, but there were significant changes in vertical force and anterior-posterior force values with normalized speed. The ground reaction force patterns in these children were characterized predominantly by normalized speed of progression and not age. The clinical relevance of these findings is that normalized speed of walking, rather than age, should be considered when comparing normal with pathological gait.

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.

Dextropropoxyphene overdose. Epidemiology, clinical presentation and management.

This paper comprehensively reviews the worldwide situation regarding acute overdosage of dextropropoxyphene (propoxyphene). The changing epidemiology of this type of poisoning over the last 20 years is described with discussion of concurrent trends and, in particular, the effects of different preventive measures adopted in various countries. The clinical pharmacology of dextropropoxyphene relevant to the clinical toxic effects resulting from acute overdosage is described, and the management is detailed. In particular, the importance of early diagnosis and treatment is stressed in view of the potentially lethal complications that may suddenly occur with this poisoning. Recommendations for the correct use of the specific narcotic antagonist, naloxone, are made, together with other intensive supportive measures. As dextropropoxyphene is frequently taken together with other toxic agents, the concomitant effects of alcohol and sedative drugs are described and the treatment of paracetamol (acetaminophen) in combination with dextropropoxyphene is emphasised. The most effective preventive measures for the future are suggested, but caution is advised regarding the prescription for 'at risk' patients of alternative analgesics, which may be no safer in overdosage.

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.

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.

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.

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.

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.

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.

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.