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Biomedical subjects

D A Warrell

Publications and source records attributed to D A Warrell.

At least 55 records · Page 3Linked to original sources
PubMed1998

Randomized comparison of intramuscular artemether and intravenous quinine in adult, Melanesian patients with severe or complicated, Plasmodium falciparum malaria in Papua New Guinea.

An open-label, randomized, controlled trial was used to compare the safety and efficacy of intramuscular artemether (a loading dose of 3.2 mg/kg, followed by 1.6 mg/kg daily for 4 days) and intravenous quinine (a loading dose of 20 mg quinine dihydrochloride/kg, followed first by 10 mg/kg every 8 h, each injection taking 4 h, for at least 48 h, and then oral quinine for a total of 7 days) in the management of strictly defined severe/complicated malaria in Melanesian adults. Four (12%) of the 33 patients who enrolled and completed follow-up died (one of the 15 who received artemether and three of the 18 who received quinine). Overall, cerebral malaria was uncommon (6%) whilst jaundice was common (76%). The time taken to clear 50% of parasites was less in those treated with artemether (median = 8 h; range = 2-24 h) than in the patients given quinine (median = 14 h; range = 2-25 h; P = 0.05). Temperature defervescence was also quicker in those treated with artemether (median = 32 hours; range = 20-112 h) than in those in the quinine group (median = 48 h; range = 28-88 h; P = 0.034). Hypoglycaemia was not observed in any patient treated with artemether but complicated therapy in 11 (79%) of the 14 patients given quinine who had not had pre-treatment spontaneous hypoglycaemia. No serious adverse effects were attributable to artemether. The Plasmodium falciparum infections observed during the 1 month of follow-up, in three patients who had received artemether and two who had been given quinine, were probably due to recrudescence. Plasmodium vivax parasitaemias were also observed during follow-up, in one or two patients in each treatment group. Artemether appears safe in Melanesian adults and is probably as effective as intravenous quinine in the treatment of severe or complicated falciparum malaria.

Adult↗
PubMed1997

Snakebite by the bushmaster (Lachesis muta) in Brazil: case report and review of the literature.

The bushmaster (Lachesis muta) of Central and South America, the world's longest pit viper, is capable of injecting a large dose of potent venom when it bites. A 28-year-old man, bitten by a 1.82 m long L. m. muta in Brazil, developed pain and oedema at the bite site, nausea, vomiting, diarrhoea and sweating. There was peripheral neutrophil leucocytosis and evidence of fibrinogen consumption with secondary activation of the fibrinolytic system. Two hours after the bite, eight ampoules of Instituto Butantan Lachesis antivenom was administered, and haemostasis was normal 24 hr later. A review of reports of 20 cases of bites in humans reliably attributed to this snake in Costa Rica, French Guiana, Brazil, Colombia and Venezuela confirms a syndrome of nausea, vomiting, abdominal colic, diarrhoea, sweating, hypotension, bradycardia and shock, possibly autopharmacological or autonomic in origin, not seen in victims of other American crotaline snakes. These, and other symptoms of bushmaster envenoming, are explained by haemorrhagic, coagulant and neurotoxic venom activities. The therapeutic efficacy of non-specific Bothrops/Crotalus polyvalent antivenoms in these cases has been unimpressive. For the treatment of bites by a snake which potentially injects a large dose (> 300 mg dry weight) of venom with a range of life-threatening activities, there is an urgent need to develop more potent specific antivenoms and to treat the dramatic and life-threatening cardiovascular symptoms.

Accidents, Occupational↗
PubMed1997

Synopsis of recent developments in venomous snake systematics.

Changes to our understanding of venomous snake systematics, and the consequent changes in the nomenclature of these animals, have traditionally been a great source of confusion among biomedical researchers. This paper aims to facilitate access to the taxonomic literature by presenting a synopsis of the changes in venomous snake systematics that have taken place recently (primarily since 1992), together with some comments on the implications of these changes for toxinologists and clinicians. Some long-standing problems in venomous snake taxonomy receive special attention. This includes Asiatic Naja, Asiatic Agkistrodon/Gloydius, Bothrops and related genera, Trimeresurus, Echis, Daboia (including Daboia russellii) and Vipera. It is hoped that this synopsis will result in the use of a more up-to-date and interpretable nomenclature for venomous snakes in the toxinological literature.

Animals↗
PubMed1997

Cerebral malaria: clinical features, pathophysiology and treatment.

Herbert Gilles played an important role in the establishment of the Wellcome-Mahidol University, Oxford Tropical Medicine Research Programme in Thailand in 1979. The randomized, placebo-controlled trial of dexamethasone in cerebral malaria that was carried out in Chantaburi in 1980 yielded results which led to the abandonment of ancillary corticosteroid therapy in this disease and contributed to a rejection of the 'permeability hypothesis'. The clinical manifestations of strictly defined cerebral malaria have not been described both in non-immune adults in Thailand and Vietnam and in African children. Clinical and histopathological studies in human patients, together with laboratory studies of cyto-adherence, malaria 'toxin' and cytokine production have provided some evidence for both the 'mechanical' and 'toxin-cytokine' hypotheses to explain the pathophysiology of this condition. Chemotherapy is challenged by the continuing evolution of antimalarial resistance. Recently, the most powerful studies ever carried out with antimalarial drugs have demonstrated that artemether and quinine achieve similar case fatalities, in the range 11%-21%, and that both drugs have some advantages and disadvantages. Further studies are needed to define the efficacy and safety of prophylactic anticonvulsants and exchange transfusion in cerebral malaria. Cerebral malaria remains a major cause of mortality and, in African children, morbidity.

Adult↗
PubMed1997

Severe cytomegalovirus infection in immunocompetent patients.

Severe cytomegalovirus (CMV) infection is rare in previously healthy immunocompetent individuals; to our knowledge, only thirty-four such cases have been reported in the worldwide literature. Multiorgan involvement was associated with a high mortality rate among these patients. Disease that clinically involves only the liver or lungs could be fatal; in contrast, none of the patients with isolated central nervous system infection died. Although few patients were treated with specific antiviral therapy, five of six patients with severe infection recovered after receiving therapy with ganciclovir or foscarnet. The rarity of severe CMV disease in immunocompetent patients probably precludes the performance of a clinical trial to evaluate the efficacy of specific antiviral therapy. However, the historically poor prognosis in the absence of such therapy suggests that rapid diagnosis of CMV disease and early instigation of specific treatment may be important.

Adolescent↗
PubMed1997

The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever.

Severe Jarisch Herxheimer reaction (J-HR) precipitated by antibiotic treatment of louse-borne relapsing fever (LBRF) is associated with a transient, marked rise in circulating tumour necrosis factor alpha (TNF alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). Ovine polyclonal anti-TNF alpha antibody fragments (Fab) were used in a randomized double blind placebo controlled trial in an attempt to prevent this reaction. Within 4 h after penicillin, in controls (n = 29), a several-fold rise in cytokines occurred, concomitant with a fall in spirochaetes and maximal clinical manifestations of the J-HR. An intravenous infusion of anti-TNF alpha Fab, 30 min before penicillin in 20 patients reduced peak plasma levels of IL-6 and IL-8 (but not IL-1 beta) compared with controls (p = 0.01 and < 0.001, respectively) and the incidence of the J-HR, indicating some neutralization of TNF alpha. An apparent fall in TNF alpha reflected interference of anti-TNF alpha in the immunoassay.

Adolescent↗
PubMed1997

Snake bites by the jararacuçu (Bothrops jararacussu): clinicopathological studies of 29 proven cases in São Paulo State, Brazil.

The jararacuçu, one of the most dreaded snakes of Brazil, southern Bolivia, Paraguay and northeastern Argentina, is a heavily-built pit viper which may grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal venom may be milked from its venom glands on a single occasion. It has accounted for 0.8% to 10% of series of snake bites in São Paulo State, Brazil. We examined 29 cases of proven jararacuçu bites recruited over a 20-year period in two São Paulo hospitals. Severe signs of local and systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding, renal failure) were seen only in patients bitten by snakes longer than 50 cm; bites by shorter specimens were more likely to cause incoagulable blood. Fourteen patients developed coagulopathy, six local necrosis (requiring amputation in one) and five local abscesses. Two became shocked and four developed renal failure. Three patients, aged 3, 11 and 65 years, died 18.75, 27.75 and 83 h after being bitten, with respiratory and circulatory failure despite large doses of specific antivenom and intensive-care-unit management. In two patients, autopsies revealed acute renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the site of the bite and disseminated intravascular coagulation. In one survivor with chronic renal failure, renal biopsy showed bilateral cortical necrosis; the patient remains dependent on haemodialysis. Effects of polyspecific Bothrops antivenom were not impressive, and it has been suggested that anti-Bothrops and anti-Crotalus antivenoms should be given in combination.

Adult↗
PubMed1997

Recent transmission of tuberculosis in a cohort of HIV-1-infected female sex workers in Nairobi, Kenya.

OBJECTIVES: To describe the epidemiological and clinical characteristics of HIV-related tuberculosis in a female cohort, and to investigate the relative importance of recently transmitted infection and reactivation in the pathogenesis of adult HIV-related tuberculosis. DESIGN: Members of an established cohort of female sex workers in Nairobi were enrolled in a prospective study. Women were followed up regularly and seen on demand when sick. METHODS: Between October 1989 and September 1992 we followed 587 HIV-infected and 132 HIV-seronegative women. Standard protocols were used to investigate common presentations. Cases of tuberculosis were identified clinically or by culture. All available Mycobacterium tuberculosis strains underwent DNA fingerprint analysis. RESULTS: Forty-nine incident and four recurrent episodes of tuberculosis were seen in HIV-infected women; no disease was seen in seronegative sex workers (P = 0.0003). The overall incidence rate of tuberculosis was 34.5 per 1000 person-years amongst HIV-infected participants. In purified protein derivative (PPD) skin test-positive women the rate was 66.7 per 1000 person-years versus 18.1 per 1000 person-years in PPD-negative women. Twenty incident cases (41%) were clinically compatible with primary disease. DNA fingerprint analysis of strains from 32 incident cases identified two clusters comprising two and nine patients; allowing for index cases, 10 patients (28%) may have had recently transmitted disease. Three out of 10 (30%) patients who were initially PPD skin test-negative became PPD-positive. Taken together, 26 incident cases (53%) may have been recently infected. DNA fingerprint analysis also identified two (50%) of the four recurrent tuberculosis episodes as reinfection. CONCLUSIONS: Substantial recent transmission of tuberculosis appears to be occurring in Nairobi amongst HIV-infected sex workers. It may be incorrect to assume in other regions of high tuberculosis transmission that active HIV-related tuberculosis usually represents reactivation of latent infection.

AIDS-Related Opportunistic Infections↗
PubMed1997

First clinical experiences with a new ovine Fab Echis ocellatus snake bite antivenom in Nigeria: randomized comparative trial with Institute Pasteur Serum (Ipser) Africa antivenom.

During the past decade, effective snake antivenoms have become scarce in northern Nigeria. As a result, many patients severely envenomed by the saw-scaled or carpet viper (Echis ocellatus), which is responsible for more than 95% of the snake bites in the region, did not receive effective treatment and mortality and morbidity increased. To combat this crisis, a new monospecific ovine Fab antivenom (EchiTab) is being developed. Its theoretical advantages over conventional equine F(ab')2 antivenom are a more rapid tissue penetration and larger apparent volume of distribution (the volume of [tissue] fluid in which the the antivenom would be uniformly distributed to achieve the observed plasma concentration). In a preliminary study, two vials (20 ml; 1.0 g of protein) of EchiTab rapidly and permanently restored blood coagulability and cleared venom antigenemia in seven envenomed patients. Four experienced early reactions that responded to epinephrine. In a randomized comparative trial of one vial (10 ml; 0.5 g protein) of EchiTab or four ampules (40 ml; 2.12 g of protein) of Institute Pasteur Serum (Ipser) Africa polyspecific F(ab')2 antivenom, there were fewer reactions, but only 36% and 35% of patients, respectively, showed permanent restoration of coagulability, with the remainder requiring further doses. This suggests that 0.5 g (one vial) of EchiTab is approximately equivalent to 2.12 g (four ampules) of Ipser Africa antivenom, and that a higher initial dose will be required for most patients. Measurements of circulating venom and antivenom levels reflected the clinical events.

Adolescent↗
PubMed1997

Tetrodotoxic poisoning from ingestion of a porcupine fish (Diodon hystrix) in Papua New Guinea: nerve conduction studies.

Near Port Moresby in Papua New Guinea, three of four adult family members who ate a porcupine fish (Diodon hystrix) were severely poisoned. Within one hour of the meal, both the mother and her older daughter had developed paraesthesiae, ataxia, hypersalivation, sweating, and had collapsed and died. The younger daughter developed similar symptoms with progressive paralysis requiring mechanical ventilation for 24 hr, but she made a complete recovery 10 days after the poisoning. In this patient, nerve conduction studies showed reduced sensory and motor conduction velocities and evoked amplitudes with gradual improvement in parallel with the patient's clinical condition, consistent with the known action of tetrodotoxin on voltage-gated sodium channels.

Action Potentials↗
PubMed1997

Sensitivity to bee and wasp venoms: association with specific IgE responses to the bee and wasp venom and HLA DRB1 and DPB1.

BACKGROUND: Stings from bees and wasps can cause systemic reactions which can be fatal in some individuals. In these venom-sensitive patients, specific IgE to the venom is produced and is considered to participate in the adverse reactions. This immune response requires antigen presentation by human leucocyte antigens (HLA) class II molecules, which includes DR and DP, which are present on antigen presenting cells. OBJECTIVE: To test for associations between HLA class II DRB1 and DPB1 alleles and life-threatening sensitivity to both bee and wasp venoms. To establish further whether any associations are independent of the atopy phenotype. METHODS: A total of 33 bee- and 44 wasp-venom-sensitive patients was studied. DRB1 genotypes were determined by single stranded oligonucleotide (SSO) probing of PCR products, and DPB1 genotypes by amplified fragment length polymorphism (AFLP) analysis. Total and specific IgE were measured using the Pharmacia Immunocap, FEIA. Patients with specific IgE to the venom antigens only were termed monosensitive and those with additional specific IgE to HDM and/or GP were termed polysensitive. RESULTS: Allele frequencies were compared to an unrelated control population. The 33 bee-sensitive patients had a greater prevalence of DRB1*07 alleles than the control subjects, 26% vs 14%, with an odds ratio (OR) of 2.1 (95% CI, 1.2-3.7, P = 0.015, corrected for multiple comparisons, Pc = ns). This association was confined to the 15 monosensitive bee patients, who had a 43% DRB1*07 allele frequency when compared with 11% in the 18 polysensitive bee patients, OR 6.1 (95% CI, 1.73-22, P = 0.004, Pc = 0.05), and when compared with a control group of non-venom subjects, 43% vs 16%, OR 3.9 (95% CI, 1.72-9.0, P = 0.002, Pc = 0.02). The 44 wasp-sensitive patients had an increase in the DRB1*11 allele when compared with the control subjects, 13% vs 6%, with an OR 2.2 (95% CI, 1.0-4.6, P = 0.04, Pc = NS), and a decreased prevalence of DRB1*04 alleles, 10% vs 19%, with an OR 0.33 (95% CI, 0.24-0.99, P = 0.04, Pc = NS), but these were not significant when multiple comparisons were taken into account. The DPB1 alleles were not significantly different between the venom sensitive patients and the controls. CONCLUSION: Patients monosensitive to bee venom had a significantly greater prevalence of DRB1*07 alleles than the non-venom, control population suggesting that IgE responses in these patients may, in part be controlled by immune response HLA class II genes. These results are also suggestive of wasp-sensitive patients having a higher prevalence of DRB1*11 and a lower prevalence of DRB1*04 than the control population.

Adolescent↗
PubMed1997

The 1996 Runme Shaw Memorial Lecture: malaria--past, present and future.

Falciparum malaria may have infected Homo sapiens (and perhaps H erectus) in the Asia Pacific region for more than 100,000 years. This estimate is based on the gene frequency of alpha-thalassaemia, the protection it affords against falciparum malaria and assumptions of untreated mortality from the infection. Up until the end of the 19th century, there was a high mortality from malaria in the coastal parts of Malaya, but the malaria control campaign, begun in 1901 at Klang, was described by Sir Ronald Ross as the first successful antimalarial work in the (then) British Empire. This was extended to Singapore in 1911. When the Far Eastern Association of Tropical Medicine held its Fifth Biennial Congress in Singapore in 1923, malaria was still a major killing disease in parts of Malaya and Sarawak. The mechanism of life-threatening malaria involves cytoadherence of parasitised erythrocytes in microvascular beds, a process enhanced by the products of macrophage activation induced by malarial pyrogen. Improvements in the chemotherapy of life-threatening falciparum malaria with chloroquine and quinine have been countered by the emergence of resistant strains. Artemisinin derivatives may become the treatment of choice during the coming decade. Apart from traditional anti-mosquito methods, control of malaria now involves the use of insecticide-impregnated bed nets, new entomological strategies, including genetic manipulation of mosquitoes and selective chemoprophylaxis. Antigenic diversity and antigenic variation of the malaria parasite have so far defeated attempts to produce an effective vaccine.

History, 19th Century↗