Berg adder (Bitis atropos): An unusual case of acute poisoning.

A 5-year-old boy presented to hospital with mild local cytotoxic and severe neurotoxic symptoms. The neurotoxic symptoms included ptosis, fixed dilated pupils and flaccid paralysis with respiratory failure. Mild hyponatraemia was also a clinical feature. After various unsuccessful treatment options were followed, the Tygerberg Poison Information Centre was contacted and a diagnosis of berg adder bite was made. Berg adder bites are uncommon and therefore not usually considered in the differential diagnosis of a patient presenting with an unexplained clinical picture. A timeous poison information helpline consultation is recommended in this situation.

Toxicovigilance. I: A survey of acute poisonings in South Africa based on Tygerberg Poison Information Centre data.

BACKGROUND: The incidence and spectrum of acute poisonings in South Africa are unknown. Poisoning data can be derived from sources such as hospital admission records and poison information centre (PIC) records. OBJECTIVES: This study was conducted to examine the extent of the problem and to identify trends and toxicovigilance issues using PIC data. METHODS: A survey was conducted based on Tygerberg Poison Information Centre (TPIC) consultations over 1 year. TPIC consultation forms were analysed for patient demographics and causes of poisoning. RESULTS: The TPIC dealt with 4 771 consultations related to human exposures to poisonous substances. The study showed that accidental exposure was more common than intentional poisoning (65.2% v. 34.8%); that 55.8% of cases were adults, of which 57.6% were females; and that 61.4% of adult cases were intentional exposures, and of these 64.3% were females. There was a predominance of accidental exposures (98.8%) and a male predominance (59.7%) in children. Categories of poisoning exposures across all age groups were non-drug chemicals (52.7%), medicines (35.2%) and biological toxins (12.6%). Pesticides (34.8%), irritant/corrosive substances (27.7%) and volatile hydrocarbons (8.3%) were the most common classes of non-drug chemical exposures. Cholinesterase inhibitors (8.8%), anticoagulant rodenticides (7.1%) and pyrethroids (5.0%) were the most commonly ingested non-drug chemicals. Aldicarb and amitraz poisoning were identified as toxicovigilance targets. Analgesics (26.1%) were the most common class of medicine-related exposure, and paracetamol (15.8%), benzodiazepines (9.2%) and antihistamines (5.2%) were the most common medicine-related exposures. CONCLUSION: The study provided information on evolving trends and identified toxicovigilance targets and the need for continuing toxicology education programmes.

Toxicovigilance. II: A survey of the spectrum of acute poisoning and current practices in the initial management of poisoning cases admitted to South African hospitals.

BACKGROUND: Initial management of acute poisoning in South African (SA) hospitals such as gastric decontamination and use of antidotes has not been evaluated relevant to current international guidelines. OBJECTIVES: The objective of this study was to conduct a toxicovigilance survey of SA hospital admissions to assess the spectrum of acute poisonings, current practices in gastric decontamination, and use of antidotes in the management of acute poisoning. METHODS: A survey was undertaken based on acute poisoning admissions to Tygerberg Academic Hospital (TAH) as well as hospital-based poisoning consultations with the Tygerberg Poison Information Centre (TPIC) over 1 year to investigate trends in admissions and the initial management of hospital admissions for acute poisoning. TAH admission details and TPIC consultation forms for hospital-based cases were analysed for patient demographics, causes of poisoning, gastric decontamination measures and use of antidotes. RESULTS: There were 662 admissions to TAH and 2 459 hospital-based TPIC consultations. Paracetamol and cholinesterase inhibitors were the most common exposures in both studies. Gastric decontamination measures were employed at TAH in 47.7% of cases and in 5.3% of hospital cases reported to the TPIC. Of these, 67.4% in the TAH study and 26.1% in the TPIC study did not comply with international guidelines. N-acetylcysteine was administered inappropriately in 22.1% of the paracetamol poisoning cases at TAH and in 1.6% in the TPIC study. Atropine was administered unnecessarily in 12 of 30 TPIC cases. CONCLUSION: This study has identified the need for directed training on gastric decontamination measures and use of antidotes and, combined with the previous study, has identified national trends in poisoning.

Stability evaluation of a prostaglandin E1 saline solution packed in insulin syringes.

This article describes the preparation and stability of a sterile prostaglandin E1 solution. The solution is packed in insulin syringes as single dose injections for the treatment of erectile disfunction. The stability of this preparation is 24 weeks when stored at 5 degrees C.

Pharmacokinetic model selection for target controlled infusions of propofol. Assessment of three parameter sets.

BACKGROUND: Computer-assisted target controlled infusions (TCI) result in prediction errors that are influenced by pharmacokinetic variability among and within patients. It is uncertain whether the selection of a propofol pharmacokinetic parameter set significantly influences drug concentrations and clinical acceptability. METHODS: Thirty patients received similar propofol TCI regimens after being randomly allocated to one of three parameter sets. Arterial and venous concentrations were measured and prediction errors calculated from pooled and intrasubject data. RESULTS: Arterial propofol concentrations in the Dyck group revealed greater bias (mean 43%) than did those in the Marsh (-1%) and Tackley (-3%) groups. The Dyck group also showed greater inaccuracy (mean:47%) than the Marsh (29%) and Tackley (24%) groups. There was little tendency for measured concentrations to vary from targeted values over time (divergence). Variability about an observed mean in individual patients (wobble) was low. Venous propofol concentrations were initially much less than arterial concentrations, but this difference decreased over time. CONCLUSIONS: Although it may be preferable to administer propofol TCI by using a locally derived parameter set, it is acceptable to use a model from elsewhere. The Marsh and Tackley models produced equally good performance and are appropriate for propofol TCI within the range of 3-6 micrograms/ml. The Dyck model was less accurate at maintaining anesthetic concentrations, possibly because it was derived from low concentrations. Concentrations in blood, the most sensitive indicators of performance, demonstrated differences among the parameter sets. Clinically, TCI worked well, and by clinical criteria, the choice of pharmacokinetic model did not appear to make a difference.

Evaluation of a high-performance thin-layer chromatographic technique for the determination of salbutamol serum levels in clinical trials.

Salbutamol concentrations were determined by high-performance thin-layer chromatography in the sera of two sets of ten volunteers at hourly intervals for 6 h after taking one 8-mg slow-release tablet. The influence of time lapse in processing of serum samples, i.e. centrifugation, extraction and chromatography, was studied. A statistical significant instability of salbutamol in the sera of patients was found which was not present in standard drug-free serum samples spiked with salbutamol and used for construction of standard curves.

Inhaled and oral salbutamol: how effective in the prophylaxis of asthma?

Inhaled and oral salbutamol were compared in 12 asthmatic patients for prophylaxis in antigen-induced asthma. The patients were pretreated with 0.2- and 1.0-mg doses of inhaled salbutamol and with the standard oral 4- and 8-mg slow-release (SR) salbutamol preparations. Bronchodilatation was monitored over the ensuing 3 h and protection against antigen challenge at the end of the period. On each study day the degree of baseline airway hyperreactivity was determined by histamine challenge. Precautions were taken during the antigen challenge to ensure a reproducible response. Blood levels of salbutamol were monitored at hourly intervals for the 3 h after treatment and during the asthmatic reaction subsequent to challenge. Both the 0.2- and 1.0-mg inhalations caused immediate bronchodilation as compared to a placebo (p less than 0.05), but only the 1.0-mg dose protected subjects against antigen challenge (p less than 0.05). In comparison to the placebo, no bronchodilatation was achieved with the standard 4-mg oral preparation in spite of measurable blood levels, nor were the patients protected against antigen challenge at 3 h after pretreatment. However, the 8-mg SR salbutamol caused significant bronchodilatation within 2 h and suppressed antigen challenge responses as compared to placebo (p less than 0.05). It can be concluded that doses of inhaled salbutamol higher than the conventional 0.2- or the standard 4-mg oral preparations are required to protect asthmatics against inadvertent antigen exposure. In patients who are unable to use inhalers effectively, the SR preparation can be considered as an alternative.

Application of flow cytochemistry to the evaluation of HL-60 differentiation.

The application of flow cytochemistry to the analysis of previously unreported differentiation-related functions, was investigated in HL-60 cells. After 72 and 96 h of continuous RA-exposure mean peroxidase index and percentage of large unstained cells were significantly less than in time-related control cultures. Percentage neutrophils were significantly increased in induction cultures. Although total cell number increased with time in both control and induction cultures, the increase was less in induction cultures. These findings are consistent with the differentiation-associated growth limitation and with the decreased myeloperoxidase activity reported in RA-treated cultures in other studies. We propose that in the context of RA-induced HL-60 maturation, flow cytochemistry could become a useful adjunct to conventional functional differentiation assessment.

Effect of various propofol plasma concentrations on regional myocardial contractility and left ventricular afterload.

The cardiovascular effects of propofol infusions, designed to maintain constant plasma concentrations, were examined in an open-chested pig model. Regional myocardial contractility was measured with the end-systolic pressure-length relationship (Ees) and left ventricular afterload quantified by the effective arterial elastance (Ea). The propofol plasma concentrations in this study varied between 0 and 7.73 (SEM 0.96) micrograms/mL. A significant correlation for the increasing propofol plasma concentration and a decrease in myocardial contractility (P = 0.0056) was demonstrated, and the Ea remained constant. This gave rise to a reduction in stroke volume (P = 0.002) and, combined with a decrease in the heart rate (P = 0.0001), led to a reduction in the cardiac output (P = 0.0001). When the propofol infusion was stopped, myocardial contractility did not recover in parallel with the decrease in plasma propofol concentration.

The binding of thyroid hormone receptors to DNA.

The behaviour of tri-iodothyronine (T3)- and thyroxine (T4)-receptor complexes when bound to native DNA-cellulose is reported. Equal and large proportions of both T3- and T4-receptor complexes bind to DNA but although T3-receptor complexes are 99% recoverable by 0.5 M NaCl buffer elution, only 60-70% of the T4-receptor complexes are regained. The balance appears as free T4, apparently released as the T4-receptor complexes bind to the DNA whilst the corresponding receptor remains bound. This effect is independent of T4-receptor complex/DNA ratio up to ca. 4 fmol/micrograms DNA, of the presence of an equal amount of unoccupied receptor and of an eight-fold concentration range of both T4-receptor complex and DNA at a fixed ratio, in the cellulose matrix. Pre-formed receptor-DNA material, likewise, only accepts some 60% of the expected quantity of T4 whereas the capacity for T3 appears to be similar to that of free receptors.

The specific binding of the thyroid hormones to matrix isolated from rat liver nuclei.

Specific binding sites for the thyroid hormones have been demonstrated in the liver nuclear matrix, a structural framework of the nucleus. When labelled 3,5,3'-tri-iodo-L-thyronine ([125I]T3) is injected into rats, 5% of the total nucleus bound T3 is bound to the matrix after 1 hour. However, when either isolated nuclei or isolated nuclear matrices were incubated with [125I]T3 in vitro, a 3- to 7-fold greater number of specific T3 binding sites were revealed in the nuclear matrix. The properties of the matrix-associated thyroid hormone binding sites were investigated in vitro. These binding sites showed limited capacity and high affinity for T3; the equilibrium association constant (Ka) was 1,3 x 10(9) M-1 and the binding capacity was 20,2 fmol T3 per 100 microgram matrix protein.