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Biomedical subjects

D A Warrell

Publications and source records attributed to D A Warrell.

At least 199 records · Page 11Linked to original sources
PubMed1983

An economical regimen of human diploid cell strain anti-rabies vaccine for post-exposure prophylaxis.

Vaccine regimens using 0.1 ml human diploid cell strain vaccine (HDCSV) given intradermally (id) in single and multiple sites, or with aluminum hydroxide adjuvant given subcutaneously (sc), were compared with the regimens of HDCSV and Semple vaccine currently suggested by WHO. Some groups were also given human rabies-immune globulin (HRIG). Neutralising antibody titres were monitored for 3 months. Antibody was detected earliest in subjects given 0.1 ml HDCSV id at each of eight sites. The highest antibody titres from day 14 onwards were found after intramuscular (im) administration of HDCSV, but the multiple-site id regimen, which requires only one quarter of the volume of vaccine required for the im regimen, gave similar results, provided that a booster was given on day 91. This finding suggests that a treatment schedule based on this regimen would be suitable for post-exposure prophylaxis. Adjuvanted vaccine gave similar results to the same amount of antigen given id. Semple vaccine produced the lowest titres. HRIG, given at the high dose of 40 IU per kg, suppressed the antibody response to some of the regimens.

Adolescent↗
PubMed1983

Severe hypoglycemia and hyperinsulinemia in falciparum malaria.

We studied the occurrence, clinical manifestations, and mechanism of hypoglycemia in patients with falciparum malaria in eastern Thailand. Hypoglycemia, which was often severe and recurrent, occurred in 17 patients, including 12 in a series of 151 patients with cerebral malaria. Thirty episodes were investigated. Plasma concentrations of insulin and C peptide were inappropriately high, and lactate and alanine concentrations were significantly higher than in patients with falciparum malaria who were normoglycemic (P less than 0.05). Sixteen patients had received quinine; plasma quinine and insulin concentrations were correlated at the time of hypoglycemia (P = 0.007). In seven healthy fasting volunteers intravenous quinine increased the mean plasma insulin concentration (+/- S.D.) from 8.9 +/- 3.1 to 17.1 +/- 8.4 mU per liter (P = 0.02) and reduced the mean plasma glucose concentration from 88 +/- 20 to 68 +/- 23 mg per deciliter (P = 0.002). Our observations indicate that in falciparum malaria quinine-induced insulin secretion may precipitate hypoglycemia, but other factors, including the large glucose requirements of the malaria parasites may also contribute. This important complication, associated with pregnancy and severe disease, must be excluded in all patients with falciparum malaria who have impaired or deteriorating consciousness.

3-Hydroxybutyric Acid↗
PubMed1983

Meptazinol diminishes the Jarisch-Herxheimer reaction of relapsing fever.

Naloxone, an opioid antagonist, and meptazinol, an opioid antagonist with agonist properties, were tested in a double-blind placebo-controlled trial in 24 Ethiopian patients with louse-borne relapsing fever. The potentially fatal Jarisch-Herxheimer reaction (J-HR), which invariably follows tetracycline treatment of the disease, was unaffected by naloxone, 30-40 mg intravenously, but was diminished by meptazinol, 300-500 mg intravenously. Compared with naloxone and placebo, meptazinol reduced the clinical severity of the reaction, significantly delayed and shortened its chill phase, delayed the rise in temperature, and reduced peak temperature and changes in pulse and respiratory rates and leucocyte count. High-dose corticosteroids given before or at the time of tetracycline treatment failed to alter the reaction, which is thought to result from release of endotoxin-like substances. Meptazinol is the first effective treatment for the J-HR of louse-borne relapsing fever. This finding suggests a role for endogenous opioids in the pathogenesis of the J-HR.

Adolescent↗
PubMed1983

Do patients with cerebral malaria have cerebral oedema? A computed tomography study.

Computed tomography of the brain in 10 patients with severe cerebral malaria, 5 of whom died, showed evidence of cerebral oedema in only 2 fatal cases. Small areas of altered density were seen in 4 cases; these were not associated with focal neurological signs and were still visible in convalescent scans in 2 survivors. 4 patients, including 1 of the fatalities, had completely normal scans. Cerebral oedema may occur in severe cerebral malaria but is not a consistent feature of living patients and cannot, therefore, always be the cause of their coma.

Acute Disease↗
PubMed1983

Severe neurotoxic envenoming by the Malayan krait Bungarus candidus (Linnaeus): response to antivenom and anticholinesterase.

Five patients were bitten by the Malayan krait Bungarus candidus (Linnaeus) in eastern Thailand or north western Malaya. Two patients were not envenomed but the other three developed generalised paralysis which progressed to respiratory paralysis in two cases, one of which ended fatally. One patient showed parasympathetic abnormalities. Anticholinesterase produced a dramatic improvement in one patient. Another patient probably benefited from paraspecific antivenom. The efficacy of antivenoms and adjuvants such as anticholinesterases in patients with neurotoxic envenoming requires further study.

Adolescent↗
PubMed1983

Pathophysiology and immunology of the Jarisch-Herxheimer-like reaction in louse-borne relapsing fever: comparison of tetracycline and slow-release penicillin.

Twelve men with louse-borne relapsing fever were treated with single doses of procaine penicillin plus aluminum monostearate (PAM) intramuscularly or of tetracycline intravenously. All patients experienced a definite Jarisch-Herxheimer-like reaction. Fever and spirochetemia were significantly prolonged and peak temperature was lower and occurred later in the PAM-treated group. Peak pulmonary ventilation, metabolic rate, and arterial PO2 were significantly higher in the tetracycline-treated group. Circulatory changes were similar in the two groups but were prolonged in the PAM-treated patients. Thus, tetracycline is recommended for treatment because it is more rapidly effective in eliminating Borrelia spirochetes and produces a reaction no more stressful physiologically than the one after PAM. There was no evidence of complement activation, and there was no change in immunoglobulin levels throughout the reaction. Immune complexes were detected in serum of five patients before treatment, but in fewer patients at the peak of the reaction and subsequently.

Adult↗
PubMed1983

Quinine loading dose in cerebral malaria.

In cerebral malaria, the use of currently recommended doses of intravenous quinine may result in subtherapeutic plasma concentrations during the critical first 24 hours of treatment. A loading dose of quinine (20 mg/kg quinine dihydrochloride, equivalent to 16.7 mg/kg base, infused over 4 hours) proved a rapid and safe method of achieving plasma concentrations above the high minimum inhibitory concentrations for Plasmodium falciparum prevalent in Eastern Thailand.

Adolescent↗
PubMed1983

Retinal hemorrhage, a common sign of prognostic significance in cerebral malaria.

Retinal hemorrhages were seen in 21 patients among a group of 144 with strictly-defined cerebral malaria. Hemorrhages were multiple in 17 cases and bilateral in 14. There was subhyaloid extension in two. Soft exudates were seen in two, the retinae were considered edematous in four and in one there was bilateral papilledema. Retinal hemorrhages were significantly associated with several indices of severity of Plasmodium falciparum infection: high parasitemia with schizontemia, anemia, elevated serum creatinine and reduced plasma antithrombin III. Only two patients with hemorrhages were both severely anemic and thrombocytopenic. It is suggested that retinal hemorrhages, a frequent finding in cerebral malaria, may be visible evidence of vascular lesions involved in the pathogenesis of this condition.

Adolescent↗
PubMed1982

Dexamethasone proves deleterious in cerebral malaria. A double-blind trial in 100 comatose patients.

High-dose dexamethasone was compared with placebo in a double-blind trial involving 100 comatose patients with strictly defined cerebral malaria. The two treatment groups, whose members were six to 70 years old, proved comparable on admission. There were eight deaths in the dexamethasone group and nine in the placebo group (no significant difference; P = 0.8); at post-mortem examination the brain showed features diagnostic of cerebral malaria in all but one patient who died. Dexamethasone prolonged coma among the survivors: the interval between the start of treatment and the full recovery of consciousness was 63.2 +/- 5.9 hours (mean +/- S.E.M.) in the dexamethasone group, as compared with 47.4 +/- 3.2 hours in the placebo group (P = 0.02). Complications, including pneumonia and gastrointestinal bleeding, occurred in 26 patients given dexamethasone and 11 given placebo (P = 0.004). Only five patients had neurologic sequelae. Results were similar in a subgroup of 28 children six to 14 years old. Dexamethasone is deleterious in cerebral malaria and should no longer be used.

Adolescent↗
PubMed1982

Quinine pharmacokinetics and toxicity in cerebral and uncomplicated Falciparum malaria.

Acute pharmacokinetics of intravenously infused quinine were studied in 25 patients with cerebral malaria and 13 with uncomplicated falciparum malaria. In patients with cerebral malaria receiving the standard dose of 10 mg/kg every eight hours, plasma quinine concentrations consistently exceeded 10 mg/liter, reaching a peak 60 +/- 25 hours (mean +/- 1 S.D.) after treatment was begun and then declining. Quinine total clearances (Cl) and total apparent volumes of distribution (Vd) were significantly lower than in uncomplicated malaria (Cl, 0.92 +/- 0.42 compared with 1.35 +/- 0.6 ml/min/kg, p = 0.03; Vd, 1.18 +/- 0.37 compared with 1.67 +/- 0.34 liter/kg, p = 0.0013). There was no significant difference between the two groups in elimination half-times (t/2) or renal clearances (Cu) (t/2, 18.2 +/- 9.7 compared with 16 +/- 7.0 hours; Cu, 0.21 +/- 0.16 compared with 0.21 +/- 0.08 ml/min/kg). In nine patients studied following recovery, Cl (3.09 +/- 1.18 ml/min), Vd (2.74 +/- 0.47 liter/kg), and Cu (0.53 +/- 0.22 ml/min/kg) were significantly greater (p less than or equal to 0.0004), and t/2 was significantly shorter (11.1 +/- 4.1 hours, p = 0.006) than during the acute illness. Cu accounted for approximately 20 percent of Cl in all groups. Renal failure did not alter the disposition kinetics in cerebral malaria. There was no clinical or electrocardiographic evidence of cardiotoxicity and no permanent neurotoxicity. Quinine toxicity in cerebral malaria has probably been overemphasized. The benefits of high plasma concentrations in the acute phase of this life-threatening disease appear to outweigh the risks, particularly in view of the increasing resistance of Plasmodium falciparum to quinine in Southeast Asia.

Acute Disease↗
PubMed1981

Quinidine in falciparum malaria.

Fourteen patients with falciparum malaria were successfully treated with oral quinidine. Twelve of these patients were followed for 35 days without recrudescence. In six patients the infection had already recrudesced after antimalarial treatment, which in two cases had included a full course of quinine. Quinidine caused no cardiotoxicity, although the electrocardiogram QTc interval was prolonged by more than 25% in four patients. In-vitro cultures from nine of these patients and a further seven patients with falciparum malaria showed that the minimum inhibitory concentration was consistently lower for quinidine than for quinine. Quinidine is an effective antimalarial drug for Plasmodium falciparum infections and may be more potent than quinine.

Administration, Oral↗
PubMed1980

Comparison of Pasteur and Behringwerke antivenoms in envenoming by the carpet viper (Echis carinatus).

Bites and envenoming by the carpet viper Echis carinatus are common medical emergencies in parts of Nigeria, but the most effective use of the various commercially produced antivenoms in treatment has not been established. Pasteur Paris Echis monospecific and Behringwerke West and North Africa Bitis-Echis-Naja polyspecific antivenoms were compared in two groups of seven patients with incoagulable blood after E carinatus bites. In both groups spontaneous bleeding stopped within a few hours and local swelling subsided within two weeks after the initial antivenom injection. Pasteur antivenom (20-40 ml) restored blood coagulability within 12 hours in all cases, but 60--180 ml of Behringwerke antivenom was effective in only four cases. Persisting venom procoagulant activity was observed in the remaining three cases. Despite its potency in the mouse protection test, Behringwerke antivenom is unreliable and unpredictable in neutralising venom procoagulant in humans bitten by E carinatus.

Adult↗
PubMed1980

The structure of soluble fibrin complexes and fibrin degradation products after Echis carinatus bite.

Studies on the concentration and structure of fibrinogen, fibrinogen-fibrin soluble complexes, and fibrinogen-fibrin degradation products were made on 11 patients in Nigeria who suffered defibrination following Echis carinatus bite. Following admission, before treatment with antivenom, all patients had reduced or zero fibrinogen levels, and increased concentrations of soluble complexes and degradation products. The fibrin component of the soluble complexes, separated by fibrinogen-sepharose chromatography, consisted of both intact fibrin and fibrin degraded at the alpha-chain. After isolation by Biogel chromatography the soluble complexes were also found to contain gamma-dimer chains. The fibrinogen-fibrin degradation products consisted of several X species, Y, D and D-dimer, as well as fragment E. The major fragment in all patients was D, but a few samples contained significant quantities of D-dimer, indicating in vivo activation of factor XIII. There was evidence of degraded fibrinogen, as well as fibrin, in the soluble complexes and degradation products, suggesting that fibrinogenolysis, in addition to fibrinolysis, had occurred, probably as a result of secondary endogenous activation of the fibrinolytic system in response to defibrination.

Antivenins↗