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Biomedical subjects

D A Warrell

Publications and source records attributed to D A Warrell.

At least 37 records · Page 2Linked to original sources
PubMed2000

Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial.

BACKGROUND: Severe cardiac glycoside cardiotoxicity after ingestion of yellow oleander seeds is an important problem in rural areas of Sri Lanka. Currently, patients must be transferred to the capital for temporary cardiac pacing. We did a randomised controlled trial to investigate whether anti-digoxin Fab could reverse serious oleander-induced arrhythmias. METHODS: After a preliminary dose-finding study, 66 patients who presented to hospital with a serious cardiac arrhythmia were randomised to receive either 1200 mg of anti-digoxin Fab or a saline placebo. A 12-lead electrocardiogram, 3 min rhythm strip, and blood sample for measurement of electrolytes and cardiac glycosides were taken before treatment and at 12 timepoints thereafter. FINDINGS: 34 patients received anti-digoxin Fab and 32 received placebo. The presenting arrhythmia had resolved completely after 2 h in 15 antibody-treated patients and two controls (p<0.001); 24 and five patients, respectively, were in sinus rhythm at 8 h (p<0.001). Kaplan-Meier analysis of time to first reversal showed a significant response to anti-digoxin Fab. The heart rate increased in cases, from 49.1 per min at baseline to 66.8 at 2 h, but not in controls (50.6 per min at baseline to 51.5; p<0.001). Mean serum potassium concentrations decreased from 4.9 mmol/L to 4.1 mmol/L at 2 h in cases; no such decrease occurred in controls. INTERPRETATION: Anti-digoxin Fab fragments are a safe and effective treatment for serious cardiac arrhythmias induced by yellow oleander. Their use in small rural hospitals in Sri Lanka should minimise costly transfer of patients and reduce the numbers of deaths; however, further study will be required to confirm this reduction.

Adult↗
PubMed2000

Acute yellow oleander (Thevetia peruviana) poisoning: cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside concentrations on presentation to hospital.

OBJECTIVE: To describe the cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside levels seen in patients presenting to hospital with acute yellow oleander (Thevetia peruviana) poisoning and to compare these with published reports of digitalis poisoning. DESIGN: Case series. SETTING: Medical wards of Anuradhapura District General Hospital, Sri Lanka, and coronary care unit of the Institute of Cardiology, National Hospital of Sri Lanka, Colombo, the national tertiary referral centre for cardiology. PATIENTS: 351 patients with a history of oleander ingestion. MEASUREMENTS: ECG and blood sample analysis on admission. RESULTS: Most symptomatic patients had conduction defects affecting the sinus node, the atrioventricular (AV) node, or both. Patients showing cardiac arrhythmias that required transfer for specialised management had significantly higher mean serum cardiac glycoside and potassium but not magnesium concentrations. Although there was considerable overlap between groups, those with conduction defects affecting both sinus and AV nodes had significantly higher mean serum cardiac glycoside levels. CONCLUSIONS: Most of these young previously healthy patients had conduction defects affecting the sinus or AV nodes. Relatively few had the atrial or ventricular tachyarrhythmias or ventricular ectopic beats that are typical of digoxin poisoning. Serious yellow oleander induced arrhythmias were associated with higher serum cardiac glycoside concentrations and hyperkalaemia but not with disturbances of magnesium.

Adolescent↗
PubMed1999

Sequential randomised and double blind trial of promethazine prophylaxis against early anaphylactic reactions to antivenom for bothrops snake bites.

OBJECTIVE: To investigate the efficacy of the H1 antihistamine promethazine against early anaphylactic reactions to antivenom. DESIGN: Sequential randomised, double blind, placebo controlled trial. SETTING: Public hospital in a venom research institute, São Paulo, Brazil. PARTICIPANTS: 101 patients requiring antivenom treatment after being bitten by bothrops snakes. INTERVENTION: Intramuscular injection of promethazine (25 mg for adults and 0.5/kg for children) or placebo given 15-20 min before starting intravenous infusion of antivenom. MAIN OUTCOME MEASURES: Incidence and severity of anaphylactic reactions occurring within 24 hours after antivenom. RESULTS: Reactions occurred in 12 of 49 patients treated with promethazine (24%) and in 13 of 52 given placebo (25%); most were mild or moderate. Continuous sequential analysis indicated that the study could be interrupted at the 22nd untied pair, without preference for promethazine or placebo. CONCLUSION: Prophylaxis with promethazine does not prevent early reactions. Patients should be observed carefully during antivenom infusion and the subsequent few hours.

Adolescent↗
PubMed1999

Synopsis of recent developments in venomous snake systematics, No. 3.

We present recent findings in the systematics of venomous snakes, with emphasis on those which affect the nomenclature and our understanding of species limits in these animals. Changes in systematics reviewed here include particularly the genera Acanthophis, Elapsoidea, Bitis, Lachesis, Porthidium, Trimeresurus/Tropidolaemus and Vipera. Other new publications of more general interest to toxinologists are also presented.

Animals↗
PubMed1999

Epidemic of self-poisoning with seeds of the yellow oleander tree (Thevetia peruviana) in northern Sri Lanka.

Deliberate self-harm is an important problem in the developing world. Ingestion of yellow oleander seeds (Thevetia peruviana) has recently become a popular method of self-harm in northern Sri Lanka -- there are now thousands of cases each year. These seeds contain cardiac glycosides that cause vomiting, dizziness, and cardiac dysrhythmias such as conduction block affecting the sinus and AV nodes. This paper reports a study of the condition's mortality and morbidity conducted in 1995 in Anuradhapura General Hospital, a secondary referral centre serving 750 000 people in Sri Lanka's north central province. 415 cases were admitted to the hospital during 11 months; 61% were women and 46% were less than 21 years old. A prospective study of 79 patients showed that 6% died soon after admission. 43% presented with marked cardiac dysrhythmias which necessitated ther transfer to the coronary care unit in Colombo for prophylactic temporary cardiac pacing. The reasons for the acts of self-harm were often relatively trivial, particularly in children; most denied that they wished to die. Unfortunately, the case fatality rate for oleander poisoning in Sri Lanka is at least 10%. This epidemic is not only causing many unnecessary deaths, it is also putting immense stress on the already stretched Sri Lankan health services. There is an urgent need for an intervention which could be used in rural hospitals, thus preventing the hazardous and expensive emergency transfer of patients to the capital.

Adolescent↗
PubMed1999

Successful in vitro cultivation of Borrelia duttonii and its comparison with Borrelia recurrentis.

Borrelia duttonii, the cause of East African tick-borne relapsing fever, has until now been refractory to growth in laboratory media. This spirochaete has only be propagated in mice or by tissue culture, restricting both yield and purity of cells available for research. The successful isolation of five clinical isolates of B. duttonii from patients in Central Tanzania and their comparison with Borrelia recurrentis is reported. Electron microscopy revealed spirochaetal cells with pointed ends, a mean wavelength of 1.8 microns with an amplitude of 0.8 micron, similar to the findings for B. recurrentis. Cells contained 10 periplasmic flagella inserted at each end of the spirochaete, again comparable with the counts of 8-10 flagella found in B. recurrentis. PFGE revealed a chromosome of approximately 1 Mb, a large plasmid of approximately 200 kb, and a small plasmid of 11 kb in all strains of B. duttonii and in B. recurrentis. B. duttonii possessed a further 7-9 plasmids with sizes ranging from 20 to 90 kb. In two isolates of B. duttonii, the profiles were identical. In contrast, all 18 isolates of B. recurrentis fell into one of five plasmid patterns with 3-4 plasmids ranging from 25 to 61.5 kb in addition to those of 11 and 200 kb described above. Analysis of the SDS-PAGE profiles of B. duttonii strains revealed a high-molecular-mass band of 33.4-34.2 kDa in four strains (variable large protein, VLP) and a low-molecular-mass band of 22.3 kDa in the remaining strain (variable small protein, VSP). This resembles the protein profiles found in B. recurrentis. The G + C ratio of B. duttonii was 27.6 mol%. Nucleotide sequence of the rrs gene (16S rRNA) from four B. duttonii isolates revealed 100% identity among these strains and 99.7% homology with three strains deposited by others in GenBank. The rrs gene of eight representative clinical isolates of B. recurrentis confirmed their close similarity with B. duttonii.

Bacteriological Techniques↗
PubMed1999

A new monospecific ovine Fab fragment antivenom for treatment of envenoming by the Sri Lankan Russell's viper (Daboia Russelii Russelii): a preliminary dose-finding and pharmacokinetic study.

Russell's viper is the most important cause of life-threatening snake bite and acute renal failure in Sri Lanka. Only equine polyspecific antivenoms imported from India are available. They have not proved effective clinically or in clearing venom antigenemia and they frequently cause reactions. In an attempt to reduce mortality and morbidity, a new monospecific ovine Fab fragment antivenom (PolongaTab; Therapeutic Antibodies, Inc., London, United Kingdom) was raised against Sri Lankan Russell's viper venom. In a preliminary dose-finding study in 35 patients, an initial dose of 3-4 g restored blood coagulability permanently and stopped systemic bleeding, even in severely envenomed patients. Venom antigenemia disappeared within 1 hr of antivenom treatment but recurred, probably as a result of continued absorption of venom from the site of the bite, after the rapid clearance of therapeutic antibody. Twelve patients (34%) experienced early reactions that were usually mild and always responded to epinephrine.

Adolescent↗
PubMed1999

Polyclonal anti-tumor necrosis factor-alpha Fab used as an ancillary treatment for severe malaria.

Single doses (250, 500, 1,000, or 2,000 units/kg) of an ovine polyclonal-specific Fab fragment directed against tumor necrosis factor-alpha (TNF-alpha) were given to 17 adult patients with severe falciparum malaria immediately before treatment with artesunate in a pilot study to assess safety and optimal dosage with a view to future studies. Clinical and laboratory variables were compared with 11 controls. In the groups given Fab, there was a tendency for a faster resolution of clinical manifestations and reduction of fever but also a tendency towards longer parasite clearance times. Adverse events were more common in the control group and no early anaphylactic or late serum sickness reactions occurred in the Fab treated patients. On admission all patients had markedly elevated levels of TNF-alpha (85-1,532 ng/L) and interleukin-6 (IL-6) (30-27,500 ng/L). Also, 86% had elevated interferon-gamma (IFN-gamma) levels, 75% had increased IL-2 levels, 36% had increased IL-8 levels, and 21% had increased IL-1beta levels. Antibody treatment reduced IFN-gamma concentrations in a dose-related manner, but had no obvious effects on levels of other cytokines in this small study, although unbound TNF-alpha was undetectable after Fab treatment. Circulating concentrations of soluble E-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were not affected by Fab treatment. The Fab exhibited a two-compartment, dose-proportional kinetics with an average elimination half-life of 12.0 hr, with about 20% being excreted renally. These results encourage a randomized, placebo-controlled trial in patients with cerebral malaria and provide some guidance about dosage.

Adolescent↗
PubMed1999

Management of severe malaria.

The case fatality of WHO-defined 'severe falciparum malaria' remains unacceptably high, at 10-20%. However, a gradual decline in case fatality in adults and children treated in hospitals may reflect use of improved regimens of antimalarial chemotherapy and increased awareness of important complications of the disease. The development of severe, perhaps inevitably-fatal, malaria might be prevented by early appropriate chemotherapy of uncomplicated disease. At the most peripheral levels of the health service, suppository formulations of artemisinin derivatives can be administered even to patients who are vomiting or prostrated. At dispensaries, clinics or hospitals, where intramuscular or intravenous administration of antimalarial drugs is possible, quinine and artemisinin derivatives are the treatments of choice. There is growing evidence of the safety and efficacy of the quinine loading dose and of the use of artemether and artesunate, based on large, randomised, controlled clinical studies. No safe and effective form of prophylactic ancillary treatment has yet emerged. Results of studies of antipyretics, anticonvulsants (phenobarbitone), anticytokine/anti-inflammatory agents (anti-TNF antibodies, pentoxifylline, dexamethasone), iron chelators and hyperimmune sera have been disappointing. Only blood transfusion and treatment of respiratory, circulatory and renal failure are of obvious benefit. New ideas are needed, based on what is known of the pathophysiology of severe disease.

Adult↗
PubMed1998

Some effects of the rising case load of adult HIV-related disease on a hospital in Nairobi.

Increasing numbers of HIV-infected adults in Africa need hospital care. It remains unclear what impact this has on health care services or on how hospitals respond. The aim of this study was to describe the effects of a rising case load of adult HIV-related disease by comparing results from a prospective cross-sectional study of acute adult medical admissions to a government hospital in Nairobi conducted in 1992 with results from a previous study done in 1988 and 1989 in the same hospital, using the same study design and protocol. Data on age, gender, number admitted, length of stay, HIV status, clinical AIDS, final diagnosis, case mix, and outcome were compared. In 1992, 374 consecutive patients were admitted in 15 24-hour periods (24.9 patients/period) compared with the 1988 to 1989 study, which enrolled 506 patients in 22 24-hour periods (23.0 patients/period). Patients' age, gender, and length of hospital stay were similar in both studies. In 1992, 39% of patients were HIV-positive compared with 19% in 1988 to 1989 (p < 10(-6)); whereas seropositive admissions rose 123% between the two periods (p < .0001), HIV-negative admissions declined 18% (p < .05). Clinical surveillance for AIDS consistently identified <40% of HIV-positive patients. Irrespective of HIV status, tuberculosis and pneumococcal pneumonia were the leading diagnoses in both surveys. No change was found in the diagnoses recorded for HIV-positive patients, but in HIV-negative patients, reductions were significant in the case mix (p < .00001) and range of diagnoses (p < .001) seen in 1992. Outcome remained unchanged for HIV-positive patients with approximately 35% mortality in both surveys. Outcome significantly worsened, in relative and absolute terms, for HIV-negative patients: in 1992, mortality was 23%, compared with 13.9% in 1988 to 1989 (p < .005), with 3.5 deaths per 24-hour period in 1992 compared with 2.6 deaths per 24-hour period in 1988 to 1989 (p < .05, one-tailed). These data suggest that increasing selection for admission is taking place as demand for care increases because of HIV/AIDS. This process appears to favor HIV-positive patients at the expense of HIV-negative patients who seem to be crowded out and, once admitted, experience higher mortality rates. The true social costs of the HIV epidemic are underestimated by not including the effects on HIV-negative people.

Adult↗
PubMed1998

Neurological manifestations of falciparum malaria.

Plasmodium falciparum remains one of the most common causes of central nervous system infection worldwide. Recently, differences between the pathophysiology of cerebral malaria in African children and nonimmune adults have been discovered, new syndromes occurring after malaria infection described, and mechanisms for the pathogenesis proposed. In addition, new antimalarial agents have been examined worldwide and initial studies on supportive studies conducted. This paper reviews these new advances, putting them into the perspective of the more established knowledge.

Adult↗
PubMed1998

Synopsis of recent developments in venomous snake systematics, No. 2.

Developments in our understanding of the systematics of venomous snakes since the beginning of 1996 are discussed and reviewed with special emphasis on their relevance and implications for toxinologists and clinicians. Groups of snakes affected by recent developments include the genera Elapomorphus, Rhabdophis, Vermicella, Atheris, Daboia, Agkistrodon/Gloydius, Bothrops/Bothriopsis and Trimeresurus. Other important publications on venomous snakes are noted.

Animals↗
PubMed1998

Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever.

Massive release of tumor necrosis factor is responsible for the potentially fatal larisch-Herxheimer reaction that follows antibiotic treatment of relapsing fever due to Borrelia recurrentis. We have undertaken the quantitative purification of the components of B. recurrentis that stimulate human monocytes to produce tumor necrosis factor. We show that the predominant factor inducing tumor necrosis factor is a variable lipoprotein homologous to the variable major protein of B. hermsii. We found antibodies to different forms of variable major protein in two patients with louse-borne relapsing fever. The three purified variable major proteins studied here differ in their ability to induce tumor necrosis factor production, which may partly explain the variable clinical severity of borrelial infection. These results may be of considerable relevance for the pathogenesis of Lyme disease and other forms of human borreliosis.

Amino Acid Sequence↗