Biomedical subjects

D A Warrell

Publications and source records attributed to D A Warrell.

At least 271 records · Page 15Linked to original sources

PubMedDate not supplied

Development of renal function abnormalities following bites by Russell's vipers (Daboia russelii siamensis) in Myanmar.

Renal function was monitored in 24 patients with systemic envenoming following proven Russell's viper bite. In all patients, blood clotted within 20 min on admission. In 15 cases severe defibrination (systemic envenoming) developed during the next 3-5 d. None of the patients received antivenom before admission but enzyme-refined monospecific antivenom was given to those who developed signs of systemic envenoming. Specific antigen was detected by enzyme immuno-assay in all 21 subjects tested. Nine patients whose renal function remained normal did not develop systemic envenoming, and recovered without any treatment even though venom antigen was detectable in their serum. Ten patients developed mild renal dysfunction and systemic envenoming, but recovered after treatment with antivenom alone. The remaining 5 patients, all of whom were oliguric from admission, developed acute renal failure despite treatment with antivenom, but some recovered after peritoneal dialysis. Serum venom antigen levels were high in the last 2 groups, but there was some overlap. Albuminuria, found only in patients who became systemically envenomed, was associated with high fractional sodium excretion in those who developed acute oliguric renal failure. Albuminuria may appear before a gross clotting defect is detectable. It is an indication for antivenom and spot measurements might prove a useful early predictor of outcome.

Acute Kidney Injury↗

PubMedDate not supplied

Bites by Russell's vipers (Daboia russelii siamensis) in Myanmar: effect of the snake's length and recent feeding on venom antigenaemia and severity of envenoming.

An improved enzyme immunoassay technique (EIA) was used in the diagnosis of 311 suspected Russell's viper bite cases in Myanmar [Burma], 181 of whom (58%) had systemic envenoming. Russell's viper venom was detected in the sera of 175 (56.3%), cobra or green pit viper venoms in 4 (1.3%), and no venom in the remaining 132 (42.4). Among 175 of these patients who failed to bring the dead snake, EIA achieved a specific diagnosis of Russell's viper envenoming in 101 (58%). The serum venom antigen concentration was higher in patients with systemic envenoming than in those with local or no envenoming and it increased with the development of coagulopathy. Stomach contents were examined in 101 Russell's vipers responsible for bites. The presence of prey, usually a rodent, in the snake's stomach, indicating that it had eaten recently, did not influence the severity of envenoming, the initial venom level, or the percentage circumference increase and the extent of local swelling in the bitten limb. One hundred and fifty-five Russell's vipers responsible for bites showed a bimodal distribution of total lengths. The smaller snakes had probably been born that year. Longer snakes were responsible for more severe envenoming, a shorter interval between the bite and the detection of incoagulable blood, and more extensive local swelling with a greater percentage circumference increase of the bitten limb; but their bites were not associated with higher initial venom antigenaemia or a greater risk of developing acute renal failure.

Adult↗

PubMedDate not supplied

Rediscovery and redefinition of Malcolm Smith's Trimeresurus kanburiensis in Thailand, with a report of envenoming.

Three specimens of an apparently rare pit viper, Trimeresurus kanburiensis, previously known only from the holotype collected in 1928, were found near Kanchanaburi in western Thailand. One of the snakes had bitten a young woman on the foot. She experienced severe local pain, swelling that involved the whole of the bitten limb and beyond, local bruising, recurrent shock, peripheral leucocytosis and a mild coagulopathy, but she recovered despite the lack of specific treatment. The severity of envenoming augurs ill for a young or debilitated patient bitten by this species. During the last 20 years, the name T. kanburiensis has been used incorrectly for the medically more important species, T. purpureomaculatus. Conversely, the name T. purpureomaculatus has been misapplied to specimens of a species of viper from southern Thailand which we consider very similar to T. kanburiensis, but for which a new specific name, 'T. venustus', has been suggested recently. The rediscovery and redefinition of T. kanburiensis should prevent further confusion.

Adult↗

PubMedDate not supplied

A national hospital-based survey of snakes responsible for bites in Thailand.

Snakes which had been killed and brought to hospital with the patients they had bitten were collected in 80 district and provincial hospitals throughout 67 provinces in Thailand in order to establish the geographical distribution and relative medical importance of the venomous species. Of the 1631 snakes collected, 1145 were venomous: Malayan pit vipers (Calloselasma rhodostoma), green pit vipers (Trimeresurus albolabris) and Russell's vipers (Daboia russelii) were the most numerous, while T. albolabris, C. rhodostoma and spitting cobras ('Naja atra') were the most widely distributed. In 22 cases, non-venomous species were mistaken for venomous ones and antivenom was used unnecessarily. The Malayan krait (Bungarus candidus) was confused with B. fasciatus in 5 cases and B. fasciatus antivenom was used inappropriately. The study extended the known ranges of most of the medically-important venomous species in Thailand. Correct identification of venomous snakes is especially important in Thailand because the locally-produced antivenoms are monospecific. The technique of hospital-based collection, labelling and preservation of dead snakes brought by bitten patients is recommended when rapid assessment of a country's medically important herpetofauna is required.

Animals↗

PubMedDate not supplied

Renal ischaemia, transient glomerular leak and acute renal tubular damage in patients envenomed by Russell's vipers (Daboia russelii siamensis) in Myanmar.

Fifty-two patients who had been bitten by Russell's vipers in Myanmar developed acute renal failure (serum creatinine exceeding 1.3 mg/dL). Thirty-four of them (65%) became oliguric, but the other 18 (35%) maintained a urine output of more than 400 mL/24 h. In oliguric patients, gastrointestinal haemorrhages, renal angle tenderness and conjunctival oedema occurred more commonly, and peak serum creatinine, blood urea nitrogen and the fractional excretion of sodium were significantly higher (P < 0.01) than in non-oliguric patients, indicating a greater degree of renal damage. Urinary concentrations of beta 2 microglobulin and retinol binding protein were raised in most of the patients indicating failure of proximal tubular reabsorption of these proteins, while high urinary N-acetyl glucosaminidase concentrations were consistent with renal tubular damage. Plasma concentrations of active renin were very high, suggesting that renal ischaemia, associated with activation of the renin-angiotensin system, was involved in the development of renal dysfunction.

Acute Kidney Injury↗

PubMedDate not supplied

Neurotoxic envenoming by the Sri Lankan krait (Bungarus ceylonicus) complicated by traditional treatment and a reaction to antivenom.

A 30 year old woman bitten by a large Sri Lankan krait (Bungarus ceylonicus) developed progressive paralytic symptoms within one hour of the bite. After seeking traditional treatment her condition deteriorated and when she arrived at hospital 6 h after the bite she was drowsy, with bilateral ptosis and signs of aspiration pneumonia (a complication of traditional treatment). She developed an anaphylactic reaction after antivenom treatment and, despite treatment, had a cardio-respiratory arrest. She was resuscitated and mechanically ventilated, but remained deeply unconscious until her death 90 h after the bite. B. ceylonicus is endemic in Sri Lanka, is common in some areas, and could be mistaken for the common krait (B. caeruleus). It is doubtful whether any existing antivenom is effective against its venom.

Adult↗

PubMedDate not supplied

Accidental envenoming by a Gaboon viper (Bitis gabonica): the haemostatic disturbances observed and investigation of in vitro haemostatic properties of whole venom.

We report the successful treatment of envenoming by the Gaboon viper (Bitis gabonica) and include results of in vitro investigations of the haemostatic properties of the whole venom. The patient was admitted to casualty soon after the bite with chest tightness, dizziness, nausea and swelling at the site of the bite and was treated immediately with polyspecific antivenom, hydrocortisone, chlorpheniramine and antibiotics. Results of haemostatic investigations were essentially normal on admission but on day 3 the thrombin time became prolonged and was associated with significant hypofibrinogenaemia and elevated D-dimers. Factors V and VIII, antithrombin III and protein C levels and platelet number were not significantly reduced. The haemostatic disturbances persisted for more than 24 h despite treatment with blood products (16 units of cryoprecipitate, 2 units of fresh frozen plasma and 6 units of platelet concentrate). Resolution of the abnormalities occurred only after administration of a further dose of antivenom. The period of hypofibrinogenaemia occurred at a time when venom antigen was undetectable in plasma by enzyme-linked immunosorbent assay. Studies in vitro with whole venom and a panel of amidolytic substrates commonly employed for measurement of haemostatic proteins revealed significant activity of venom with substrates sensitive to kallikrein and plasmin. The venom inhibited washed platelet aggregation induced by collagen, thrombin, arachidonic acid and the calcium ionophore A23187 in a dose-dependent manner.

Adult↗

PubMedDate not supplied

Brucellosis: imported and laboratory-acquired cases, and an overview of treatment trials.

Following the successful eradication of Brucella abortus infection in cattle, human brucellosis in England and Wales has become an uncommon imported disease. Culture of the organism presents a major laboratory hazard, and difficulties in identification may occur using a biochemical test-strip method. An overview of recent treatment trials of brucellosis indicates that regimens combining streptomycin and doxycycline are associated with a higher success rate (judged by the frequency of treatment failure and relapse following therapy) than combinations of rifampicin and doxycycline.

Adolescent↗

PubMedDate not supplied

Analysis of referral letters to assess the management of poisonous snake bite in rural Papua New Guinea.

A prospective series of patients envenomed after snake bite was seen at Port Moresby General Hospital (PMGH), Papua New Guinea, between January 1991 and December 1992. Referral letters were received with 60 of the patients who had been initially seen at a health centre. These letters were analysed in conjunction with our own clinical observations. The importance of non-clotting blood and local lymphadenopathy as early signs of systemic poisoning did not appear to be universally recognized by staff in health centres. In some cases, no attempt was made to transfer the patient to hospital until signs of neurotoxicity were established with potentially dangerous delay. Analysis of both hospital and health centre records suggests that the majority of deaths which occurred in Central Province, Papua New Guinea, during the period of the study were due to delay in transfer to hospital. We suggest that all patients with unequivocal signs of envenoming in Central Province, Papua New Guinea, should be transferred to PMGH as soon as possible. Antivenom should also be given as soon as possible, but this does not remove the need for immediate transfer.

Antivenins↗

PubMedDate not supplied

Haemostatic dysfunction and acute renal failure following envenoming by Merrem's hump-nosed viper (Hypnale hypnale) in Sri Lanka: first authenticated case.

A five years old boy was bitten by a Merrem's hump-nosed viper (Hypnale hypnale) in Central Province, Sri Lanka. He developed local swelling, incoagulable blood, thrombocytopenia, bleeding into the gastrointestinal tract, and acute renal failure. Treatment with Serum Institute of Indian polyspecific antivenom (specific for venoms of cobra, common krait, Russell's viper and saw-scaled viper) had no effect on the coagulopathy, which persisted for more than a week. The boy recovered after 27 d in hospital, during which he was treated with peritoneal dialysis for renal failure. Laboratory studies demonstrated that the venom of H. hypnale was procoagulant, fibrinolytic and aggregated platelets. This first authenticated case of life-threatening acute renal failure and haemostatic disturbances caused by H. hypnale, a species responsible for 27% of snake bites in Sri Lanka, demonstrates the need for a new antivenom with specific activity against the venom of this species.

Acute Kidney Injury↗

PubMedDate not supplied

Electrophysiological findings in patients envenomed following the bite of a Papuan taipan (Oxyuranus scutellatus canni).

Electrophysiological studies were done on patients with systemic neurotoxicity following the bite of a Papuan taipan (Oxyuranus scutellatus canni). Evoked compound muscle action potentials decreased and increased in tandem with clinical deterioration and recovery. Nerve conduction velocities did not change in envenomed patients and were consistent with control studies. Repetitive nerve stimulation studies showed decremental responses in envenomed patients with post-tetanic potentiation followed by post-tetanic exhaustion. The findings are consistent with studies in vitro which suggested that the major action of neurotoxins in Australian taipan venom is at the synapse. The observation that electrophysiological data correlate closely with the clinical condition of the patient has potential application in the assessment of interventions in the management of snake bite victims.

Action Potentials↗

PubMedDate not supplied

Failure of 3,4-diaminopyridine and edrophonium to produce significant clinical benefit in neurotoxicity following the bite of Papuan taipan (Oxyuranus scutellatus canni).

Progressive systemic neurotoxicity is a common feature in patients envenomed following the bite of a Papuan taipan (Oxyuranus scutellatus canni). Respiratory paralysis, which commonly results, accounts for considerable morbidity and mortality. Established neurotoxicity does not respond to antivenom. In this study, a combination of clinical and electrophysiological variables was used to assess the effect of edrophonium and 3,4-diaminopyridine in patients with significant neurotoxicity. Both drugs produced minor electrophysiological and clinical changes in envenomed patients. This effect was maximal when the 2 drugs were used in combination, but was insufficient to be of significant clinical benefit. Neither drug can be recommended for use in the management of Papuan taipan bite.

4-Aminopyridine↗

PubMedDate not supplied

The epidemiology of snake bite in Central Province and National Capital District, Papua New Guinea.

Snake bite is an important medical problem in some areas of Papua New Guinea and appears to be most common in the Central Province and National Capital District. The overall incidence for Central Province is 215.5 per 100,000 population, but Kairuku subprovince has an incidence of 526 per 100,000, which is amongst the highest in the world. The clinical pattern of envenoming also varies within the Province, suggesting that different species of snake may be responsible for bites in different areas. Most envenomed patients are bitten during daylight on the lower limb and are rarely able to describe the snake. The mortality rate in Central Province is 7.9 per 100,000; most patients die from ventilatory failure due to severe neurotoxicity. Mortality might be reduced by increased use of compression bandaging as a first aid measure, earlier treatment with antivenom and earlier referral to hospital.

Adolescent↗

PubMedDate not supplied

The efficacy of antivenom in the treatment of bites by the Papuan taipan (Oxyuranus scutellatus canni).

A prospective series of 156 patients systemically envenomed following the bite of a Papuan taipan (Oxyuranus scutellatus canni) were studied. All patients were treated with appropriate antivenom and clinical course and outcome were compared. The proportion of patients requiring intubation was significantly smaller, and the time to resolution of neurotoxicity and discharge from hospital significantly shorter, in patients receiving antivenom no more than 4 h after the bite. No significant difference in outcome was demonstrated between patients receiving antivenom at various times after 4 h. No difference was demonstrated in the times to restoration of coagulability between the 2 groups. The only significant difference between a small number of patients given 2 vials of antivenom and patients given a single vial at the same time after envenoming was a marginally shorter duration of intubation in those who required it. The study suggests that, to achieve significant clinical benefit in Papuan taipan bite, antivenom must be given as early as possible.

Animals↗

PubMedDate not supplied

An open, randomized comparative trial of two antivenoms for the treatment of envenoming by Sri Lankan Russell's viper (Daboia russelii russelii).

Russell's viper (Daboia russelii russelii) is an important cause of morbidity and mortality in Sri Lanka. In a study in 1985, Haffkine equine polyspecific antivenom in doses up to 20 g proved ineffective in clearing antigenaemia and caused a high incidence of anaphylactoid reactions. A new, monospecific ovine Fabantivenom (Polonga TAb) has been developed against the venom of Sri Lankan Russell's viper and, to assess its safety and efficacy, we carried out (in 1997) an open, randomized comparison of this with the Haffkine antivenom currently in use in the country. Patients with systemic envenoming following Russell's viper bite were randomized to receive an initial intravenous dose of either 1 g of Polonga TAb (n = 23) or 10 g of Haffkine antivenom (n = 20). One dose of Polonga TAb permanently restored blood coagulability in only 9 (41%) of 22 patients and 13 needed repeated doses, whereas the majority (14/20; 70%) had restored coagulability after 1 dose of Haffkine antivenom. There was a tendency towards more rapid resolution of local swelling and systemic manifestations in the Haffkine group. Venom antigenaemia was eliminated more quickly in the Haffkine group and ovine Fab was cleared from the circulation more rapidly than equine F(ab')2. To evaluate safety, patients were closely observed for adverse reactions. Following a severe reaction with Haffkine antivenom all subsequent patients in this group were treated prophylactically with hydrocortisone and chlorpheniramine. Despite this, the incidence of adverse reactions was significantly higher in the Haffkine group compared with the PolongaTAb group (81% compared with 48%) and 4 patients had a severe anaphylactic reaction in the former group. In conclusion, the new antivenom is safer than Haffkine antivenom but, to avoid repeated doses, an initial dose higher than 1 g is needed in the treatment of Sri Lankan Russell's viper envenoming. The safety of this larger dose is the subject of further studies.

Adolescent↗

PubMedDate not supplied

Envenoming by Bothrops jararaca in Brazil: association between venom antigenaemia and severity at admission to hospital.

The association between the clinical severity of Bothrops jararaca envenoming at admission and serum venom and plasma fibrinogen concentrations before antivenom administration is reported in 137 patients admitted to Hospital Vital Brazil, Instituto Butantan, São Paulo, Brazil, between 1989 and 1990. Other variables such as age, gender, site of the bite, use of tourniquet and the time interval between the bite and start of antivenom therapy, spontaneous systemic bleeding, and the 20 minute whole blood clotting test (20WBCT) at admission showed no association with either severity or serum venom antigen concentration (SVAC). Mean SVAC in patients with mild envenoming was significantly lower than in the group with moderate envenoming (P = 0.0007). Patients with plasma fibrinogen concentrations > 1.5 g/L had a lower mean SVAC than patients with plasma fibrinogen concentrations < or = 1.5 g/L (P = 0.02). Those admitted with a tourniquet in place had significantly higher plasma fibrinogen concentrations than those without a tourniquet (P = 0.002). A multiple logistic regression model showed independent risk factors for severity: bites at sites other than legs or forearms, SVACs > or = 400 ng/mL, and the use of a tourniquet. Rapid quantification of SVAC before antivenom therapy might improve initial evaluation of severity in B. jararaca bites.

Adolescent↗

PubMedDate not supplied

Exposure to Cryptococcus neoformans var. gattii--a seroepidemiological study.

An enzyme-linked immunosorbent assay was developed to study prevalence of immunoglobulin G (IgG) antibody to non-capsular Cryptococcus neoformans var. gattii antigen in a population of healthy Papua New Guinea (PNG) controls and patients. Patients with acute C. neoformans var. gattii meningitis had elevated levels of IgG which declined significantly following treatment (P = 0.034). Levels in the sera of convalescent patients were significantly higher than those in PNG controls (P < 0.001), which in turn were significantly higher than in a UK control group (P < 0.001). Clear differences were observed amongst the PNG controls. Adults had significantly higher levels than children (P = 0.002) and men had significantly higher levels than women (P = 0.047). No difference was observed between levels in patient-related and unrelated controls. IgG responses in PNG controls mirror the prevalence of disease in this population. It is postulated that exposure to C. neoformans var. gattii is less common in children and women due to some as yet unidentified behavioural difference and that exposure occurs away from the home environment.

Adolescent↗

PubMedDate not supplied

Meningitis caused by Cryptococcus neoformans var. gattii and var. neoformans in Papua New Guinea.

Eleven cases of cryptococcal meningitis were diagnosed and biotyped from September 1991 to August 1992 in Papua New Guinea (PNG). Seven isolates were Cryptococcus neoformans var. gattii from paediatric and adult patients, one with diabetes mellitus and 4 were C. neoformans var. neoformans from adults, of whom 2 had human immunodeficiency virus type 1 (HIV-1) infection, and one each had tuberculosis and Plasmodium vivax malaria. Significant clinical findings were headache, fever, meningism, vomiting, photophobia, papilloedema and cranial nerve lesions. Five patients (45.5%) died; 3 of these were adults with var. gattii and 2 were men with both var. neoformans and HIV-1 infections. This prospective tropical study documents the emergence of C. neoformans var. neoformans in patients with HIV-1 infection in a country where previously var. gattii had predominated in the immunocompetent. There has been no earlier report of cryptococcosis in an HIV-1 seropositive patient in PNG. Despite presumed exposure to both varieties of C. neoformans, var. gattii infections had been most frequent. As HIV-1 spreads, the proportion of hosts infected with var. neoformans may rise. The course of meningitis caused by the 2 varieties of C. neoformans may differ, with mortality in the tropics remaining particularly high. In PNG the environmental source of C. neoformans remains elusive.

Adolescent↗