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Biomedical subjects

D A Warrell

Publications and source records attributed to D A Warrell.

At least 127 records · Page 7Linked to original sources
PubMed1989

Reduced hepatic blood flow and intestinal malabsorption in severe falciparum malaria.

We have studied intestinal function and liver blood flow in Thai adults with complicated and uncomplicated falciparum malaria. The absorption of 3 orally administered test sugars, D-xylose, 3-O-methyl-D-glucose, and L-rhamnose, was greatly reduced in complicated malaria, while the lactulose/rhamnose absorption ratio was significantly increased. Hepatic blood flow was concomitantly reduced in severe malaria. These deviations reverted to normal in convalescence. Neither sugar absorption nor liver blood flow was reduced in uncomplicated falciparum malaria.

Adolescent↗
PubMed1989

Treatment of severe malaria.

In the treatment of severe Plasmodium falciparum infection antimalarial drugs should, ideally, be given by controlled rate intravenous infusion until the patient is able to swallow tablets. In cases where infection has been acquired in a chloroquine resistant area, and where it has broken through chloroquine prophylaxis or where the geographical origin or species are uncertain, quinine is the treatment of choice. When access to parenteral quinine is likely to be delayed, parenteral quinidine is an effective alternative. A loading dose of quinine is recommended in order to achieve therapeutic plasma concentrations as quickly as possible. In the case of chloroquine sensitive P. falciparum infection, chloroquine, which can be given safely by slow intravenous infusion, may be more rapidly effective and has fewer toxic effects than quinine. There is limited experience with parenteral administration of pyrimethamine sulphonamide combinations such as Fansidar, and resistance to these drugs has developed in South East Asia and elsewhere. Mefloquine and halofantrine cannot be given parenterally. Qinghaosu derivatives are not readily available and have not been adequately tested outside China. Supportive treatment includes the prevention or early detection and treatment of complications, strict attention to fluid balance, provision of adequate nursing for unconscious patients and avoidance of harmful ancillary treatments. Anaemia is inevitable and out of proportion to detectable parasitaemia. Hypotension and shock ('algid malaria') are often attributable to secondary gram-negative septicaemia requiring appropriate antimicrobial therapy and haemodynamic resuscitation. Many patients with severe falciparum malaria are hypovolaemic on admission to hospital and require cautious fluid replacement. Failure to rehydrate these patients may lead to circulatory collapse, lactic acidosis, renal failure and severe hyponatraemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Cerebral anaerobic glycolysis and reduced cerebral oxygen transport in human cerebral malaria.

In 12 patients comatose with cerebral malaria, cerebral blood flow was 52.2 (SE 4.0) ml/100 g per min, within the reported range for healthy controls, but cerebral vascular resistance was raised at 1.66 (0.19) mm Hg/ml per 100 g per min. Cerebral oxygen consumption (1.90 [0.23] ml/100 g per min), and cerebral arteriovenous oxygen content difference (3.5 [0.43] ml/dl) were subnormal, while cerebral venous pO2 (5.7 [0.2] kpA) was raised. After recovery of consciousness there were significant decreases in arterial lactate concentration (2.44 [0.45] to 1.19 [0.45] mumol/l) and cerebral lactate production (17.4 [7.9] to 5.6 [1.1] mmol/100 g per minute). These results provide evidence of cerebral anaerobic glycolysis associated with inadequate oxygen delivery to the brain consistent with either inhibition of cerebral oxidative metabolism or the microcirculatory obstruction envisaged in the "mechanical" hypothesis for cerebral malaria.

Adolescent↗
PubMed1988

Single dose phenobarbitone prevents convulsions in cerebral malaria.

48 patients over 6 years of age with strictly defined cerebral malaria were randomised to receive either a single intramuscular injection of phenobarbitone (3.5 mg/kg) or placebo in a double-blind, placebo-controlled study. Phenobarbitone significantly reduced the incidence of subsequent convulsions from 54% to 12.5%, without adverse effects. A single intramuscular injection of phenobarbitone is a simple, cheap, and effective method for prevention of convulsions in cerebral malaria.

Adolescent↗
PubMed1988

Factors contributing to fatal snake bite in the rural tropics: analysis of 46 cases in Thailand.

Records of 46 cases of fatal bites by identified snakes from 15 provincial hospitals throughout Thailand contained sufficient information for detailed analysis. Bungarus candidus and Calloselasma rhodostoma were each responsible for 13 deaths, Naja kaouthia for 12, Vipera russelli for 7 and B. fasciatus for one. Major causes of death among elapid victims were respiratory failure (26) and complications of prolonged mechanical ventilation (10), and among viper victims shock (12), intracranial haemorrhage (9), complications of local wound necrosis (7) including tetanus (2), and renal failure (2). Factors contributing to fatal outcome included inadequate dose of antivenom (15 cases), misidentification of the snake leading to use of the wrong antivenom (12), problems associated with mechanical ventilation (10), and delayed arrival in hospital after traditional (herbal) treatment (10). Similar problems have been identified in other tropical countries. Education of medical staff and the patient population at highest risk could reduce snake bite mortality.

Adolescent↗
PubMed1988

Quinine pharmacokinetics in cerebral malaria: predicted plasma concentrations after rapid intravenous loading using a two-compartment model.

To investigate the toxic potential of rapid intravenous quinine administration in severe malaria, the pharmacokinetic properties of low-dose quinine dihydrochloride injection (4 mg/kg body weight, equivalent to 3.3 mg base/kg) followed one hour later by infusion of 16 mg/kg over 3 h were studied in 7 patients with cerebral malaria. Plasma quinine concentrations closely followed a bi-exponential decline. Both the volumes of the central compartment (mean +/- SD: 0.17 +/- 0.10 litre/kg) and total volumes of distribution (0.74 +/- 0.30 litre/kg) were significantly smaller than those previously reported for healthy subjects. Based on the derived pharmacokinetic parameters, predicted plasma quinine concentrations following intravenous injection of the standard therapeutic dose (10 mg salt/kg) over 10-20 min are potentially toxic in severe malaria. Further reductions in administration time would produce disproportionately higher plasma quinine concentrations, especially as the distribution half-time (2.3 +/- 3.2 min) is approached. A theoretical regimen designed to achieve therapeutic, non-toxic plasma quinine concentrations promptly would be 7.0 mg quinine dihydrochloride/kg over 30 min. A subsequent maintenance infusion of 10 mg/kg over 4 h would allow for drug elimination and acute changes in pharmacokinetic parameters due to resuscitation and rehydration.

Adolescent↗
PubMed1988

The hyaluronidase activities of some Southeast Asian snake venoms.

The hyaluronidase activities of venoms of snakes indigenous to Southeast Asia were investigated. With the exception of the venom of the Malayan krait Bungarus candidus, the elapid venoms had either little or no hyaluronidase activities, whereas the viperid venoms possessed considerable activity. A component of Russell's viper venom with hyaluronidase activities had a mol. wt of approximately 14,000. Neither MP4, a monoclonal antibody raised against the purified Russell's viper venom hyaluronidase toxin, nor a monospecific polyclonal antivenom neutralized the hyaluronidase activities of this purified hyaluronidase component of crude Russell's viper venom. The Russell's viper venom hyaluronidase activities was labile on heating and storage. The significance of these observations to envenomation and antivenom production is discussed.

Animals↗
PubMed1988

Mepacrine accumulation during treatment of chloroquine-resistant falciparum malaria.

Oral mepacrine dihydrochloride, 200 mg (158 mg of the base) six-hourly for five doses followed by 100 mg (79 mg of the base) eight-hourly for six days (half dosage for those less than or equal to 50 kg) was given to 21 patients with high-grade chloroquine-resistant falciparum malaria in eastern Thailand. Fifteen patients (71%) had a clinical response [fever clearance time of 81 +/- 35 hours (mean +/- S.D.)] and 13 (62%) had complete clearance of parasitaemia (clearance time 92 +/- 42 hours). Two patients were cured, but 11 patients returned with recurrent parasitaemia between 11 and 40 days after starting treatment. Five patients had an R2 response and three had an R3 response. Mepacrine retains some activity against chloroquine-resistant falciparum malaria but it cannot be recommended for use in Thailand. The doses used, which are those also recommended for giardiasis, led to progressive and potentially toxic mepacrine accumulation. Further evaluation of regimens which produce safer plasma concentration profiles is needed.

Adolescent↗
PubMed1988

Pharmacokinetics of chloroquine in Thais: plasma and red-cell concentrations following an intravenous infusion to healthy subjects and patients with Plasmodium vivax malaria.

1. Chloroquine diphosphate (15 mg base kg-1) was given by constant rate intravenous infusion to two groups of Thai subjects. Eleven were patients with malaria (10 with Plasmodium vivax and one case with Plasmodium malariae) and 10 were healthy normal volunteers. 2. Plasma and packed red-cell concentrations of chloroquine, electrocardiographic intervals, arterial blood pressure and pulse were measured at frequent intervals. 3. Peak plasma concentrations at the end of the infusion ranged from 979 to 2,900 ng ml-1 in the malaria patients. In the group of healthy subjects the range was 550-2,200 ng ml-1. Values for terminal elimination rate constant, (lambda z) plasma clearance (CL), initial volume of distribution (V1) and volume of distribution at steady state (Vss) were calculated. For the healthy subjects, mean estimates of these parameters were lambda z = 0.062 +/- 0.030 day-1, CL = 597 +/- 238 ml min-1, V1 = 0.66 +/- 0.71 l kg-1 and Vss = 132 +/- 50 l.kg-1 For the group of malaria patients, the corresponding values were lambda z = 0.055 +/- 0.032 day-1, CL = 535 +/- 246 ml min-1, V1 = 0.74 +/- 0.75 l kg-1 and Vss = 136 +/- 64 l kg-1 There was no statistically significant difference in the estimates for any parameter between groups (P less than or equal to 0.05). 4. Chloroquine concentrations in packed red blood cells consistently exceeded those in plasma and showed no consistent change with time throughout the period of study in either group. The median value for the red cell to plasma ratio was between 3 and 4 in each group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Haemostatic disturbances in patients bitten by Russell's viper (Vipera russelli siamensis) in Burma.

Patients who are severely envenomed by Russell's viper develop DIC which is frequently associated with spontaneous bleeding and incoagulable blood. These haemostatic disturbances may be responsible for death or organ/tissue damage both through haemorrhage and microvascular occlusion by fibrin thrombi. The most striking laboratory features of the coagulopathy developing after Russell's viper bite in the 42 patients studied were depletion of fibrinogen (mean 0.09 g/l, range 0-0.6), factor V (6.5 u/dl, range 0-17), factor X (35 u/dl, range 1-85), factor XIIIa (57 u/dl, range 15-82), plasminogen (61 u/dl, range 10-92), antiplasmin (36 u/dl, range 14-62). Protein C (49 u/dl, range 15-100) and platelets (104 x 10(9)/l, range 25-197). Intense fibrinolytic activity was detected in all cases with marked elevation of FDPs (1614 micrograms/ml, range 350-3000), a large proportion of which were cross-linked (1058 micrograms/ml, range 38-3000). The monospecific Burmese antivenom appeared to be very effective in neutralizing the venom procoagulants and in restoring blood coagulability. Moreover, the unexpectedly normal level of AT III provides a theoretical basis for the use of heparin to enhance the inactivation of those serine proteases present before antivenom administration.

Adolescent↗
PubMed1988

Lymphocyte responsiveness to a candidate malaria sporozoite vaccine (R32tet32) of individuals with naturally acquired Plasmodium falciparum malaria.

Lymphocyte proliferative responses to the candidate malaria sporozoite vaccine antigen R32tet32 were evaluated in 29 patients with acute Plasmodium falciparum malaria, 20 convalescent patients, 11 nonimmune individuals, and 22 healthy residents of two endemic malarious areas in Thailand. The results indicate that 14 of 20 (70%) convalescent patients and 14 of 22 (64%) residents of endemic areas responded to the R32tet32 antigen. However, only 8 of 29 (28%) patients with acute P. falciparum malaria responded. When 4 of the convalescent patients who remained in a malaria-free area were restudied 5-10 months after the acute infection, they were either not responsive or their responses had greatly diminished. These findings show that sensitization to R32tet32 occurs following a natural P. falciparum infection, but the cellular immune response to sporozoite antigens may be short-lived and may be suppressed during acute P. falciparum malaria.

Acute Disease↗
PubMed1988

Rapid diagnosis of rabies and post-vaccinal encephalitides.

In an attempt to establish the diagnoses of rabies post-vaccinal encephalitis (PVE) and early rabies encephalitis, paired serum and CSF levels of rabies neutralizing antibody (Rab) and rabies specific-IgM (RIgM) were compared in 12 PVE, 10 rabies and five control patients with similar presenting clinical features. Rapid methods of rabies antigen detection were evaluated in 17 patients. All 12 PVE patients had Rab in their serum and in eight it was also present in the CSF. These same eight had RIgM in the serum, and in seven also in the CSF. The CSF antibodies may have originated in the plasma since six patients had a high albumin quotient indicating leakage across the blood-brain barrier. Among the rabies patients, only the two vaccinated ones had serum Rab; this was also detected in the CSF of one and RIgM was in the CSF of the other. A raised IgG Index, indicating intrathecal synthesis of IgG was seen in five of 12 PVE patients. This did not correlate with the presence of CSF rabies antibody, suggesting production of antibody to other vaccine antigens of neural origin. The diagnosis of rabies encephalitis in life was made by antigen detection in a skin biopsy. No false positive results occurred and the method was as efficient as immunofluorescence of a post-mortem brain biopsy.

Adolescent↗
PubMed1988

Paralysis, rhabdomyolysis and haemolysis caused by bites of Russell's viper (Vipera russelli pulchella) in Sri Lanka: failure of Indian (Haffkine) antivenom.

In Sri Lanka, Russell's viper, Vipera russelli pulchella, kills more people than any other species of snake. At Anuradhapura in the dry central zone of the island we studied 23 patients with systemic envenoming after proven bites. Seventy-three per cent had swelling at the bite site. Neurotoxicity was the commonest sign of systemic envenoming: 82 per cent had external ophthalmoplegia and 77 per cent had ptosis. Incoagulable blood was found in 59 per cent but only 36 per cent had spontaneous bleeding. Other signs included generalized muscle tenderness (32 per cent), black urine (27 per cent) and persistent oliguria (9 per cent). Laboratory studies showed evidence of a severe clotting disorder: fibrinogen was often depleted as were factors V and X. Fibrin degradation products, including cross-linked moieties, were grossly elevated, clear evidence for enhanced fibrinolysis. Intravascular haemolysis, unrelated to G6PD deficiency, was often present. Myoglobin was detected in the plasma of all 19 patients tested (range 100- greater than 8000 ng/ml) and in the urine in 14 of 18 patients (110- greater than 16,000 ng/ml). Venom antigen (16.5-702 ng/ml) was detected by specific ELISA in the serum of all patients. Its concentration fell with the administration of 50-200 ml of Haffkine polyspecific antivenom raised against Indian venoms. Complete permanent clearance of venom antigen from the circulation was seen in only one of 21 patients who were followed until discharge. Blood coagulability was restored between one and 25 h (mean 8.8) after the first dose of antivenom in the 12 surviving patients whose clotting defect could be followed; no dramatic reversal of neuromyotoxic signs was seen. Haffkine antivenom thus has limited efficacy against systemic poisoning by Russell's viper in Sri Lanka.

Adolescent↗
PubMed1988

Plasmodium falciparum: inhibition/reversal of cytoadherence of Thai isolates to melanoma cells by local immune sera.

The effect of sera on the cytoadherence in vitro of Plasmodium falciparum-infected erythrocytes to melanoma cells was examined. Sera from 19 healthy individuals living in endemic malarious areas in Thailand and 24 patients with P. falciparum malaria were tested against four local P. falciparum isolates. Out of 57 sera examined, 12 (21%) showed significant inhibition (greater than 50%) of cytoadherence for at least one isolate. Anti-malarial IgG antibody titres were determined for all 57 sera and although 11 of the 12 inhibitory sera had relatively high titres, 36 out of 47 sera with similarly high titres showed no significant inhibitory activity. Convalescent sera were no more effective than corresponding acute sera in inhibiting the cytoadherence of erythrocytes infected with any of the four heterologous isolates examined. Sera which significantly inhibited cytoadherence were also capable of reversing cytoadherence, and pooled plasma, from healthy individuals living in malarious areas, was effective in significantly reversing the in vitro cytoadherence of all the five parasite isolates examined. The results confirm the antibody mediated strain-specific nature of the inhibition of cytoadherence and stress the difficulty in selecting immune sera potentially useful for the immunotherapy of cerebral malaria patients in Thailand.

Animals↗
PubMed1987

Acute and chronic pituitary failure resembling Sheehan's syndrome following bites by Russell's viper in Burma.

Pituitary function was investigated in 9 patients in shock after Russell's viper bites and in 24 individuals who had been severely envenomed 2 weeks to 24 years previously. 3 out of 9 patients had hypoglycaemia and inappropriately low serum cortisol, plasma growth hormone, and plasma prolactin concentrations. 4 who died had pituitary haemorrhage and 1 had adrenal haemorrhage as well. Of the 24 who had apparently recovered from bites, 7 had clinical features of hypopituitarism and no response in plasma growth hormone or prolactin concentrations to symptom-producing insulin-induced hypoglycaemia. 4 of these 7 had a sluggish serum cortisol response to 'Synacthen Depot' and 5 had an abnormal cortisol response to hypoglycaemia. 4 men with symptoms who were tested had low serum testosterone concentrations; serum thyroxine was also low in these men but not in 2 women with menstrual disturbances and impaired insulin responses. Of the 17 individuals without clinical evidence of endocrine disease, 4 had pituitary hormonal abnormalities. Russell's viper envenoming may thus produce a disorder resembling Sheehan's syndrome.

Acute Disease↗
PubMed1987

Dynamic alteration in splenic function during acute falciparum malaria.

Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated 51Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes [mean +/- SD] vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.

Adult↗
PubMed1987

Detection of venom by enzyme linked immunosorbent assay (ELISA) in patients bitten by snakes in Thailand.

The ability of an enzyme linked immunosorbent assay (ELISA) to detect venom was evaluated in 251 patients bitten by four of the commonest poisonous snakes in Thailand. Serum was tested only from patients who brought the snakes that had bitten them. About one third of all bitten patients had detectable venom antigenaemia, though a smaller proportion were symptomatic. Serum venom concentrations on admission correlated with the severity of clinical manifestations. The test was sensitive and specific even for specimens that had been collected and stored under suboptimal conditions. The technique is suitable for forensic use in cases of suspected snakebite. The combination of snake identification and venom antigen detection should be a more reliable means of studying the epidemiology of snakebite than the measurement of venom antibodies in a population.

Adolescent↗