W. J. du Plooy

Poisoning with Boophane disticha: a forensic case

Scales from the bulb are traditionally used as wound dressing after circumcision and as general wound dressing. Concoctions of the bulb taken orally cause sedation, analgesia, visual hallucinations, irrational behaviour, coma or death. A man ingested 150 ml of a concoction to see who placed a spell on him. He started to hallucinate, thinking that somebody was attacking him. He pulled his gun and fired shots randomly, killing one person and injuring others. A gas chromatograph/mass spectrometer was used to analyze a sample of the concoction. The sample contained buphandrin, buphanine and crinamidine (alkaloids) and eugenol. Buphanine has a pharmacological action similar to that of hyoscine and, when ingested in toxic quantities, leads to excitement, agitation, hallucinations and coma. Eugenol is a volatile oilwithanalgesicproperties.Althoughitcould notbe proved that the concoction was only from Boophane disticha, the components were similar to those found in Amaryllidaceae to which Boophane belongs. The mans behaviour could be ascribed to the ingestion of compounds found in B. disticha.

The dose-related hyper-and-hypokalaemic effects of salbutamol and its arrhythmogenic potential

1 The hypokalaemic effect of salbutamol after more than 30 min of administration has been well described. A hyper‐and‐hypokalaemic effect for adrenaline has been reported, but no such hyperkalaemic effect for salbutamol. 2 The possible hyper‐and‐hypokalaemic effects of salbutamol with the concomitant potential for pro‐arrhythmia were assessed in the baboon (Papio ursinus). 3 Male and femal baboons were anaesthetized with ketamine (15 mg kg−1) and maintained with 6% pentobarbitone as spontaneously breathing animals. Six baboons in each group received either 10, 100 or 500 μg kg−1 salbutamol i.v. Lead II of the ECG and femoral i.a. blood pressure were recorded continuously for 10 min. Arterial blood samples were collected at 0 min and then after 3 and 10 min of salbutamol administration. 4 All the animals developed sinus tachycardia (above 200 beats min−1) within 30 s of each dose of salbutamol administration and the high heart rate persisted throughout the experiment. All the animals were hyperkalaemic after 3 min and hypokalaemic after 10 min for each dose of salbutamol. Left ventricular conduction defects were seen in 3 animals during the hyperkalaemic phase. No arrhythmia was seen during the hypokalaemic phase. 5 Salbutamol has a transient hyperkalaemic and a more prolonged hypokalaemic effect in the baboon. The hypokalaemia could not be associated with arrhythmia although conduction defects were associated with the hyperkalaemia. 6 Since salbutamol is used as a bronchodilator in asthmatic patients and to treat acute hyperkalaemia, it is suggested that caution should be exercised when using salbutamol in high doses to treat acute asthma especially during the first few minutes of administration. The finding of hyperkalaemia with salbutamol questions its use in the treatment of hyperkalaemia.

The cumulative dose response effect of eicosapentaenoic and docosahexaenoic acid on blood pressure, plasma lipid profile and diet pattern in mild to moderate essential hypertensive black patients

In this study eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were given in a cumulative manner, every 6 weeks, starting with 10 mg, then 100 mg, 1000 mg and 10,000 mg EPA daily to mild to moderate essential hypertensive black patients. The corresponding DHA doses were 3, 33, 333 and 3333 mg. A control group was given olive oil as placebo for the entire 24 weeks. The placebo group had lower diastolic and systolic blood pressures after 24 weeks than the EPA and DHA group. No effect was seen on plasma triglycerides, cholesterol, HDL-cholesterol and gamma-glutamyltranspeptidase at any stage of the trial. In the EPA group plasma free-EPA increased significantly from 1000 mg onwards and plasma free-arachidonic acid (AA) decreased after 1000 mg EPA. No other plasma free essential fatty acid changed during the trial, although the HDL:cholesterol increased slightly but non-significantly with an increase in EPA and DHA. No significant changes in diet pattern or body mass was observed. It is therefore concluded that EPA and DHA supplementation had no beneficial effects in mild to moderate essential hypertensive black patients except for a lowering of plasma AA.

Paraffin poisoning in children: what can we do differently?

Abstract Background: The purpose of this study was to describe the occurrence, health cost and management of paraffin poisoning in a rural South African hospital. Methods: A retrospective study was undertaken of 145 children admitted with a diagnosis of paraffin poisoning at Philadelphia Hospital, Mpumalanga from January 2000 to June 2001. A pre-tested form was used to collect data from the admission files. Where applicable, the Chi-square test or t-test was used to determine statistical significance. Results: Children younger than five years of age were affected significantly more than those older than five years of age (91% vs. 9%, p<0.001), and boys were affected more than girls (58% vs. 42%, p=0.034). The average length of stay and cost of treatment were 2.5±2 days and R617.24 respectively. Prophylactic antibiotics were prescribed in 86% of cases (125/145) and the average number of medications prescribed per child was 3.5±1.8. Conclusions: Although no mortality was reported, paraffin poisoning contributed substantially to the morbidity of, health expenditure for and antibiotic overuse in these children. Provision of child-resistant paraffin container caps, retraining of doctors on appropriate antibiotic use and community education are necessary and crucial in reducing the occurrence of paraffin poisoning in children.

Some adverse cardiodynamic effects of prostaglandin E2 in congestive heart failure

The cardiodynamic effects of prostaglandin E(2) (PGE(2)) were studied in both healthy sheep and in animals with congestive heart failure (CHF). Merino ewes were equipped surgically with high fidelity micromanometers and left ventricular pressures measured. Heart rate, left ventricular systolic and end-diastolic pressures, +dP/dt and T(ln) were calculated on a computer from the recorded pressure curves. The paired t-test was used to determine the statistical significance of the differences. PGE(2) (25 mu g/kg) significantly improved the cardiac contractility and relaxation rate of healthy sheep and significantly reduced the heart rate, while the loading conditions under which the heart operates were not significantly affected. In contrast to healthy sheep, PGE(2) significantly reduced the contractility and relaxation rate of sheep with congestive heart failure and significantly increased the preload while heart rate and afterload were significantly reduced. The study suggests that despite the promising vasodilatory, positive inotropic and relaxation rate actions of PGE(2) in normal hearts, PGE(2) might not be a suitable therapeutic agent for CHF, because of the worsening effect it has on the cardiodynamics and loading conditions of the failing heart.

Penbutolol in the Treatment of Mild to Moderate Essential Hypertension in Black South Africans

The antihypertensive effects of penbutolol, a nonselective beta‐adrenoceptor antagonist with intrinsic sympathomimetic activity, was assessed in nonobese black South Africans aged 25 to 65 years with uncomplicated mild to moderate essential hypertension. After a 4‐week placebo run‐in period 50 patients entered a randomized placebo‐controlled study with a crossover design. For 8 weeks they received a once daily dose of 40 mg penbutolol (or placebo) which was increased to 80 mg per day for the next 4 weeks in poor responders. This was followed by a 4‐week placebo washout period after which a crossover of treatment was achieved and a second 12‐week period of treatment initiated. Thirty‐five patients completed the whole study and in 15 patients diastolic blood pressure was reduced below 95 mm Hg. The mean systolic pressures of these patients decreased by 21 mm Hg and their mean diastolic pressure decreased by 11 mm Hg during treatment with penbutolol. These results suggest that penbutolol monotherapy is an alternative therapeutic approach to hypertension in black South Africans.

Cardiodynamic improvement following PGE1 administration in sheep with congestive heart failure.

The cardiodynamic effects of Prostaglandin E1 were studied in sheep with congestive heart failure. Six Merino ewes were equipped surgically with high fidelity micromanometers and left ventricular pressures measured. Heart rate, left ventricular systolic and end-diastolic pressures, [+dP/dt]max and a single-exponential time constant (T) were calculated on a computer from the recorded pressure curves and the Wilcoxon signed rank test used to determine the statistical significance of the differences. Prostaglandin E1 (20 micrograms.kg-1) significantly improved left ventricular contractility and relaxation rate as seen respectively from [+dP/dt]max and the single-exponential time-constant and reduced the afterload conditions under which the heart operated, during various stages of congestive heat failure, without significant tachycardia during the more advanced stages of the disease. The results show that [+dP/dt]max increased between 16% (stage 4) and 38% (stage 1); T shortened between 14% (stage 4) and 25% (stage 1) and left ventricular systolic pressure decreased between 14% (stage 4) and 21% (stage 1) when prostaglandin E1 was administered during four stages of left ventricular pump failure, which ranged from a 20% decrease in [+dP/dt]max (congestive heart failure stage 1) to a 50% decrease in [+dP/dt]max (congestive heart failure stage 4). In contrast to normal animals, prostaglandin E1 caused an increase in left ventricular end-diastolic pressure during the more advanced stages of pump failure. Nevertheless the favourable cardiodynamic changes brought about by prostaglandin E1 administration might contribute, together with afterload reduction, to a general haemodynamic improvement during congestive heart failure.

Effect of gammalinolenic acid, dihomogammalinolenic acid, ascorbyl-6-gammalinolenic acid and ascorbyl-6-dihomo gammalinolenic acid on histamine- and methacholine-induced contraction of the isolated guinea pig tracheal chain

The relaxant effects of gammalinolenic acid (GLA) and dihomo gammalinolenic acid (DGLA) were compared to the relaxant effect of arachidonic acid (AA). The effect of the combination of ascorbate to form the novel drugs ascorbyl-6-gammalinolenic acid (ascorbyl-6-GLA) and ascorbyl-6-dihomo gammalinolenic acid (ascorbyl-6-DGLA) were investigated and the role of the epithelial cells was determined. Salbutamol was used as control. The isolated tracheas of six to eight guinea pigs were used in each experiment and suspended in organ baths filled with Krebs-Henseleit solution and aerated with 95% O2 and 5% CO2. The relaxant effects produced for histamine-contracted preparations were as follows: AA=71.2+/-0.2%, GLA=55.2+/-4.2%, DGLA=69.8+/-3.9%, ascorbyl-6-GLA =26.2+/-5.1% and ascorbyl-6-DGLA=54.5+/-2.4%. For methacholine-contracted preparations: AA=46.6+/-3.2%, GLA=55.0+/-9.5%, DGLA=61.8+/-2.7%, ascorbyl-6-GLA=40.0+/-8.0% and ascorbyl-6-DGLA=88.0+/-15.3%. Ascorbyl-6-GLA and ascorbyl-6-DGLA had mainly a decreased relaxant effect compared to GLA and DGLA, except ascorbyl-6-DGLA after methacholine-induced contraction, which showed a significant increased relaxant effect. The removal of the epithelium showed decreased relaxant effects for the drugs except AA, which showed increased values after methacholine contraction. Histamine-contracted preparations showed varied results. Ascorbyl-6-GLA showed an increased relaxant effect, DGLA was unaffected with no additional effect, and AA, GLA and ascorbyl-6-DGLA showed decreased relaxant effects. In conclusion, it is clear that the contractant and the availability of epithelial cells could ultimately determine the results, though the mechanism remains very complex. The benefit of added ascorbate is still unclear and warrants more investigation.

A comparison of the effects of digoxin and digitoxin on systolic time intervals and colour vision

SummaryAnimal studies suggest that for the same inotropism hydrophilic cardiac glycosides produce greater depression of atrioventricular (AV) conduction than lipophilic ones. This has been explained on the basis of a greater vagomimetic effect with hydrophilic agents and a greater sympathomimetic effect with lipophilic agents.In this randomized, cross-over study we investigated the effects of placebo, digoxin (relatively hydrophilic), and digitoxin (relatively lipophilic) in twelve healthy volunteers. For both drugs steady-state serum concentrations in the mid-therapeutic range were achieved.Both drugs produced the same positive inotropic effect as measured by systolic time intervals (QS2c). There was a trend for digoxin to have a greater effect on AV conduction than digitoxin.After atropine or propranolol there was no difference between the effect of the two cardiac glycosides on AV conduction. No significant effects on colour vision were seen. We conclude that, there do not seem to be pharmacodynamic differences between digoxin and digitoxin at mid-therapeutic serum concentrations.

Effects of digoxin and acetyl-digitoxin on basal and CO2-stimulated ventilation

SummaryEight healthy volunteers were studied to ascertain the effect of digoxin and the relatively more lipophylic cardiac glycoside, acetyl-digitoxin on ventilation. Baseline ventilation as well as the response to the inspiration of 2.2% and 4.8% carbon dioxide were assessed. Digoxin produced a depression of minute volume and oxygen consumption whereas acetyl-digitoxin produced the opposite effect. This could be the result of a relatively greater vagomimetic effect with digoxin and a greater symphatomimetic effect with acetyl-digitoxin. These findings might have clinical implications in cardiac patients who have pulmonary disease.