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Biomedical subjects

D Warrell

Publications and source records attributed to D Warrell.

10 recordsLinked to original sources
PubMed1997

Identification of phospholipase A2 and neurotoxic activities in the venom of the New Guinean small-eyed snake (Micropechis ikaheka).

The Papua New Guinean small-eyed snake (Micropechis ikaheka) is recognised as a cause of life-threatening envenoming in certain parts of New Guinea. The clinical features suggest the presence of toxins acting at the neuromuscular junction and on muscle. We have used the mouse phrenic nerve hemidiaphragm preparation, a phospholipase A2 assay, and 125I-neurotoxin-binding radioimmunoassays to look for toxic activities in the crude venom and in preliminary high-performance liquid chromatography (HPLC) fractions. Micropechis ikaheka venom at 1 and 3 micrograms/ml completely abolished nerve-evoked muscle twitch within 70 min at 37 degrees C. There was also a sustained contracture of the muscle and some reduction in twitch tension evoked by direct stimulation; these were explained by the presence of phospholipase A2 activity. The venom inhibited the binding of 125I-alpha-bungaro-toxin to detergent-extracted human muscle acetylcholine receptor (AChR), and inhibited acetylcholine receptor function in a muscle cell line. It also inhibited binding of 125I-omega-conotoxin GVIA to detergent-extracted human frontal cortex voltage-gated calcium channels, but this appeared to be dependent on the phospholipase A2 activity. Identification of the main neurotoxic fractions following HPLC are shown.

Animals↗
PubMed1997

Borrelia recurrentis characterization and comparison with relapsing-fever, Lyme-associated, and other Borrelia spp.

Borrelia recurrentis, the cause of louse-borne relapsing fever, has until recently been considered noncultivable, which has prevented characterization of this spirochete. We successfully cultivated 18 strains from patients with louse-borne relapsing fever and present the initial characterization of these isolates. Electron microscopy revealed spirochetal cells with pointed ends, an average wavelength of 1.8 microns, an amplitude of 0.8 micron, and 8 to 10 periplasmic flagella. The G+C ratio was 28.4 mol%. Whole DNA-DNA hybridizations showed similarity between the isolates of B. recurrentis but not with Borrelia hermsii, Borrelia parkeri, Borrelia turicatae, or the Lyme-associated borreliae. Sequencing studies of both the flagellin and 16S RNA genes revealed that the greatest similarity was between B. recurrentis and Borrelia duttonii. Analysis of the sodium dodecyl sulfate-polycarylamide gel electrophoresis profiles of strains revealed four groups based on the position of a major protein band (one of the groups showed some heterogeneity and was subdivided into four subgroups). Pulsed-field gel electrophoresis revealed five distinct patterns.

Borrelia↗
PubMed1996

Cognitive behaviour therapy for the chronic fatigue syndrome: a randomized controlled trial.

OBJECTIVE: To evaluate the acceptability and efficacy of adding cognitive behaviour therapy to the medical care of patients presenting with the chronic fatigue syndrome. DESIGN: Randomised controlled trial with final assessment at 12 months. SETTING: An infectious diseases outpatient clinic. SUBJECTS: 60 consecutively referred patients meeting consensus criteria for the chronic fatigue syndrome. INTERVENTIONS: Medical care comprised assessment, advice, and follow up in general practice. Patients who received cognitive behaviour therapy were offered 16 individual weekly sessions in addition to their medical care. MAIN OUTCOME MEASURES: The proportions of patients (a) who achieved normal daily functioning (Karnofsky score 80 or more) and (b) who achieved a clinically significant improvement in functioning (change in Karnofsky score 10 points or more) by 12 months after randomisation. RESULTS: Only two eligible patients refused to participate. All randomised patients completed treatment. An intention to treat analysis showed that 73% (22/30) of recipients of cognitive behaviour therapy achieved a satisfactory outcome as compared with 27% (8/30) of patients who were given only medical care (difference 47 percentage points; 95% confidence interval 24 to 69). Similar differences were observed in subsidiary outcome measures. The improvement in disability among patients given cognitive behaviour therapy continued after completion of therapy. Illness beliefs and coping behaviour previously associated with a poor outcome changed more with cognitive behaviour therapy than with medical care alone. CONCLUSION: Adding cognitive behaviour therapy to the medical care of patients with the chronic fatigue syndrome is acceptable to patients and leads to a sustained reduction in functional impairment.

Adaptation, Psychological↗
PubMed1992

Ovarian cancer family and prophylactic choices.

A subject from a family with ovarian cancer who has developed bilateral medullary carcinoma of the breast at the age of 40 is presented. The family is consistent with dominant inheritance of ovarian cancer and 12 female family members at 12.5%, 25%, and 50% risk, including our case, have undergone bilateral prophylactic oophorectomy and been given hormone replacement therapy. Despite the risk of further primary tumours of the breast our patient chose to have treatment with wide excision and radiotherapy. The implications for screening, prophylaxis, and hormone replacement therapy for this family are discussed.

Adult↗
PubMedDate not supplied

Towards optimal regimens of parenteral quinine for young African children with cerebral malaria: the importance of unbound quinine concentration.

Young African children with severe malaria are given quinine using a regimen designed for Thai adults. We measured quinine in the blood, plasma and plasma water of young children in Kenya after rapid intravenous and intramuscular dosing, and calculated the therapeutic range of unbound quinine. The peak plasma quinine concentration after rapid intravenous dosing was 12.3 +/- 3.7 mg/L (mean +/- SD), 43% higher than in adults given the same regimen previously; this was due to a smaller apparent volume of distribution in the children. The therapeutic range of unbound quinine was calculated as 0.2-2.0 mg/L. Simulations of unbound quinine were made for the standard quinine regimen: unbound drug concentrations rose above the therapeutic range after each dose. The possible risks of quinine-induced visual impairment are discussed. Alternative, lower dose regimens for young African children with severe malaria are described.

Child↗
PubMedDate not supplied

Electrocardiographic abnormalities in patients bitten by taipans (Oxyuranus scutellatus canni) and other elapid snakes in Papua New Guinea.

Envenoming by a number of species of snake may affect the myocardium or cause electrocardiographic changes; several different mechanisms have been proposed. In a prospective study of snake bite in Papua New Guinea, electrocardiographic changes were observed in 36 of 69 patients (52%) envenomed by the taipan (Oxyuranus scutellatus), 2 of 6 (33%) envenomed by death adders (Acanthophis sp.) and one envenomed by the brown snake (Pseudonaja textilis). Septal T wave inversion and bradycardias, including atrioventricular block, were the commonest abnormalities. There was no haemodynamic deterioration. The cause of these changes is uncertain; only 2 of 24 patients (8.3%) with electrocardiographic changes had markedly elevated plasma concentrations of cardiac troponin T, a sensitive and specific marker of myocardial damage. This suggests that myocardial damage is uncommon following bites by these species. Electrocardiographic abnormalities are most likely to have been caused by a direct toxic effect of a venom component upon cardiac myocyte function; in taipan bites, taicatoxin, a calcium channel blocker, might be responsible.

Animals↗