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Biomedical subjects

D A Warrell

Publications and source records attributed to D A Warrell.

At least 181 records · Page 10Linked to original sources
PubMed1985

Bites by Russell's viper (Vipera russelli siamensis) in Burma: haemostatic, vascular, and renal disturbances and response to treatment.

Of 123 patients with proved Russell's viper bite, 28% showed no evidence of envenoming, 28% had local swelling alone, but 44% had systemic envenoming manifested by incoagulable blood (100% of those admitted before treatment), thrombocytopenia (26%), spontaneous systemic bleeding (20%), hypotension (35%), evidence of increased capillary permeability (24%), and oliguria (44%). Patients with systemic envenoming usually had more local swelling than those without, but 5 had no local signs. Snake length correlated with the amount of local swelling, but snakes causing systemic envenoming were no longer than those causing local or no envenoming. Burma Pharmaceutical Industry monospecific antivenom was rapidly effective in restoring blood coagulability but did not prevent the development of renal failure even when given within 4 h of the bite. Hypotension responded to volume expanders (11/19 cases) and dopamine (6/7 cases) but not to naloxone (0/3) or high-dose methylprednisolone (0/5). The 10 deaths (8%) were attributed to hypotension, pituitary haemorrhage, and renal failure.

Adolescent↗
PubMed1985

Intravenous amodiaquine and oral amodiaquine/erythromycin in the treatment of chloroquine-resistant falciparum malaria.

In eastern Thailand, 14 adults with moderately severe falciparum malaria were treated with intravenous amodiaquine dihydrochloride, loading dose 10 mg base/kg infused over 4 h followed by three further intravenous infusions of 5 mg base/kg at 24, 48, and 72 h. All patients were clinically cured--mean fever clearance time 37.8 h (range 24-60), mean parasite clearance time 64.9 h (18-164). There were no serious toxic effects. 33 patients aged over 5 years with uncomplicated falciparum malaria were given oral amodiaquine dihydrochloride (mean total dose 41 mg base/kg over 3 days) combined with erythromycin estolate (mean dose 48 mg base/kg daily for 5 days). 2 patients failed to respond. In the other 31 patients mean fever clearance time was 55.9 h (range 10-104) and mean parasite clearance time was 65.4 h (40-120). In both studies, more than half the patients followed-up had recurrent parasitaemia but reinfection could not be excluded. Parasites isolated from 18 patients were highly resistant to chloroquine in vitro.

Administration, Oral↗
PubMed1985

Quinine and severe falciparum malaria in late pregnancy.

Quinine dihydrochloride was given intravenously to 12 women with severe falciparum malaria in the third trimester of pregnancy. The initial dose consisted of 10 or 20 mg salt/kg over 4 h and was followed by 10 mg salt/kg every 8 h until patients were fit to swallow, when quinine sulphate tablets were given. Uterine activity showed little or no change despite rising quinine concentrations. Of 3 patients in labour, 2 proceeded normally while a third had a successful caesarean section for fetal distress. Late (type II) decelerations of the fetal heart rate were recorded in 6 patients before treatment but in most patients signs of fetal distress diminished as the maternal temperature fell. Hypoglycaemia and hyperinsulinaemia developed in 7 patients, in 2 before quinine was started. The important toxic effect of quinine in late pregnancy is not an oxytocic action but rather its capacity to release insulin.

Adolescent↗
PubMed1985

Intravenous quinidine for the treatment of severe falciparum malaria. Clinical and pharmacokinetic studies.

Quinidine has proved more effective than quinine against chloroquine-resistant Plasmodium falciparum both in vitro and in patients with uncomplicated disease. To examine the effectiveness and pharmacokinetics of quinidine for this use, we treated 14 patients who had severe falciparum malaria with intravenous quinidine gluconate; a loading dose of 15 mg of the base per kilogram of body weight was followed by 7.5 mg per kilogram every eight hours. Two of the five patients with cerebral malaria died, but parasitemia was eliminated in the 12 survivors. Two patients had recurrent parasitemia on Days 25 and 28. Times required for parasite clearance and elimination of fever (49.4 +/- 17.8 and 69.5 +/- 18.7 hours, respectively) were comparable to those in earlier studies with a loading dose of quinine. Quinidine appears to have a larger volume of distribution than quinine. The elimination half-life was 12.8 hours, the volume of distribution was 1.68 liters per kilogram, total clearance was 1.75 ml per kilogram per minute, and urinary clearance was 0.62 ml per kilogram per minute. Electrocardiographic changes were common but there were no dysrhythmias. In two patients, blood pressure fell during the initial infusion of quinidine. Quinidine gluconate is more widely available than quinine in many countries, and our findings show that it is effective in severe falciparum malaria.

Adolescent↗
PubMed1985

Economical multiple-site intradermal immunisation with human diploid-cell-strain vaccine is effective for post-exposure rabies prophylaxis.

An economical post-exposure regimen of Mérieux human diploid-cell-strain vaccine (HDCSV) was compared with Semple vaccine (SV), the most widely used vaccine in Asia. 155 patients bitten by animals proved to be rabid received either conventional courses of SV (34 severe and 43 mild cases) or HDCSV, 0.1 ml intradermally, at eight sites on day 0, at four sites on day 7, and at one site on days 28 and 91 (36 severe and 42 mild cases). All severely bitten patients were given equine anti-rabies serum (EARS), 80 IU/kg on day 0. There were no deaths from rabies in either group. Follow-up was 97.5% at 1 year and 93% at 2 years. 88% of patients given HDCSV alone had detectable neutralising antibody on day 7 in contrast to 2% given SV alone. Antibody persisted until 1 year in all sera tested from HDCSV patients in contrast to only 48% of SV sera. The high dose of EARS resulted in pronounced suppression of response to HDCSV. There were no serious systemic side-effects but local side-effects were significantly more common in the SV group. The multiple-site intradermal HDCSV regimen was at least as effective as SV. The amount of HDCSV used was 30% of the conventional dose.

Adolescent↗
PubMed1985

Pathophysiological and prognostic significance of cerebrospinal-fluid lactate in cerebral malaria.

Cerebrospinal-fluid (CSF) lactate concentrations were elevated in all but 1 of 45 patients with cerebral malaria. They were significantly higher in patients who died (9.0 +/- 5.3 mmol/l, mean +/- SD) than in survivors (3.4 +/- 1.1 mmol/l, p = 0.0002) and had returned to normal values in each of 9 patients studied after recovery of consciousness. There was a significant negative correlation between CSF lactate and CSF glucose. All 11 patients with CSF lactate concentrations above 6 mmol/l died. CSF lactate is thus an important prognostic indicator in cerebral malaria and these findings suggest that hypoxia contributes to the pathogenesis of this disorder.

Adolescent↗
PubMed1985

Glucose and insulin homeostasis during the Jarisch-Herxheimer reaction.

Plasma concentrations of glucose and insulin were measured in ten patients during the Jarisch-Herxheimer reaction of tetracycline-treated louse-borne relapsing fever. Plasma glucose fell significantly in eight of the ten patients associated with the peak of the reaction, but plasma insulin remained low. Glucoregulation by insulin was therefore normal. This evidence questions the role of macrophage mediator-induced pancreatic insulin release in causing hypoglycaemia in borreliosis or bacterial endotoxicosis.

Adolescent↗
PubMed1985

Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects.

We have investigated the pharmacokinetics of primaquine after acute and chronic administration of the drug to five healthy Thai volunteers. After acute dosage (15 mg p.o.) mean (+/- s.d.) peak plasma concentrations of 65.0 +/- 34.7 ng ml-1 were achieved within 2 +/- 1h. Thereafter plasma drug concentrations declined monoexponentially with a mean elimination half life of 4.4 +/- 1.4 h. The mean (+/- s.d.) oral clearance was 37.6 +/- 15.5 1 h-1. These values are in broad agreement with values obtained in healthy Caucasians after administration of an equivalent dose of primaquine. Repeated dosing with primaquine had no effect on the mean pharmacokinetic parameters calculated for this drug. In contrast, individual pharmacokinetic parameters for some subjects exhibited gross and unpredictable changes after chronic dosage. The carboxylic acid metabolite of primaquine accumulated in plasma after repeated dosing such that by day 14 of chronic dosing the mean AUC (0,24) for this metabolite was 74% greater than that obtained after acute administration of primaquine.

Humans↗
PubMed1985

Intragastric mefloquine is absorbed rapidly in patients with cerebral malaria.

Mefloquine has proved effective in chloroquine- and quinine-resistant falciparum malaria, but it cannot be given parenterally. We have measured the absorption of mefloquine hydrochloride suspension (mean 15.6, range 9.7-28.6 mg/kg) given by nasogastric tube to 19 cerebral malaria patients already receiving intravenous quinine. Absorption was rapid with both dose schedules used; mean absorption half-times were 1.5 and 1.8 hr, and plasma mefloquine concentrations exceeded 200 ng/g within 3 hr of completing administration in all but one exceptionally ill patient who died 40 hr later. Steady state plasma concentrations over 7 days ranged from 300 to 1,050 (mean 561) ng/g. Bioavailability of mefloquine suspension in cerebral malaria therefore appears to be adequate for treatment in all but the most severely ill patients. Although intragastric mefloquine cannot now be recommended as an alternative to intravenous quinine for the treatment of severe chloroquine-resistant falciparum malaria, this situation could change if quinine resistance increases further.

Absorption↗
PubMed1985

Binding of quinine to plasma proteins in falciparum malaria.

Plasma protein binding of quinine was measured in 12 patients with cerebral malaria on the first and seventh day of treatment, and in 7 patients with uncomplicated falciparum malaria on admission and also one month later. Binding was significantly higher and therefore the proportion of free drug was lower in cerebral malaria patients (free: total quinine concentration; 7.2 +/- 3.5%, mean +/- SD, on admission; 7.4 +/- 5.3% on day 7) compared with uncomplicated malaria patients on admission (10.2 +/- 5.8%) or following recovery (11.0 +/- 5.5%, n = 6) P = 0.011. Binding was significantly correlated with the red cell/total concentration ratio r = 0.56, P less than 0.0001. The ratio of cerebrospinal fluid to free (unbound) plasma quinine was 0.55 +/- 0.33 which suggests that quinine does not freely cross the blood brain barrier. These findings are relevant to the interpretation of total plasma or serum concentration, and may explain the rarity of serious quinine toxicity in severe falciparum malaria.

Blood Proteins↗
PubMed1985

Lack of interferon induction in man by two rabies tissue culture vaccines.

Both neutralising antibody and interferon play a part in protection of animals against death from rabies virus infection. Interferon induction was therefore sought in 53 volunteers within 24 hours of receiving human diploid cell strain vaccine or fetal bovine kidney cell vaccine given either intramuscularly or intradermally. Repeat observations were made in 18 subjects following a second dose of vaccine seven days later. No interferon was detected in any sample tested although no subject had any detectable rabies neutralising antibody on day 0. The sensitivity of the interferon assay, and comparison with other studies are discussed. An interferon inducer suitable for human use should be sought as an alternative to, or a replacement for, passive rabies immunization.

Adolescent↗
PubMed1985

Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration.

For investigation of the pathogenesis of cerebral malaria, immediate postmortem samples from brain and other tissues of patients dying with Plasmodium falciparum malaria, with (CM) or without (NCM) cerebral malaria, were processed for electron microscopy. Counts of parasitized erythrocytes (PRBCs) in cerebral and other vessels showed that the proportion of PRBCs was higher in CM than in NCM, and also that the proportion of PRBCs was higher in the brain than in other organs examined in both CM and NCM. Cerebral vessels from CM patients were more tightly packed with RBCs than those from NCM patients, but there was no significant difference in the amount or degree of endothelial damage or numbers of vessels with endothelial pseudopodia. Fibrillar (fibrin) deposits were present in a small proportion of vessels, but no thrombosis was present. There was neither acute nor chronic inflammation, and leukocytes were absent within or outside cerebral vessels. There was no immune complex deposition in cerebral vessels. Parasites in cerebral vessels were mainly trophozoites or schizonts. Occasional RBC remnants following parasite release were seen. Some parasites were degenerate, resembling crisis forms. PRBCs adhered to endothelium via surface knobs. It is concluded that there is no evidence for an inflammatory or immune pathogenesis for human cerebral malaria and that the clinical effects probably relate to anoxia and the metabolic activities of the parasites.

Adolescent↗
PubMed1985

Factors contributing to the development of cerebral malaria. II. Endotoxin.

Limulus amoebocyte lysate test (LALT) was used to detect endotoxin-like substances in the plasma of 15 patients with cerebral malaria, 28 patients with uncomplicated falciparum malaria and 30 healthy controls. On admission, 67% of cerebral malaria patients were positive, whereas only 21.4% of uncomplicated malaria patients and none of controls were positive. Among uncomplicated malaria cases, four of eight patients with parasitaemia over 90,000/mm3 were LALT positive whereas only two of 20 patients with parasitaemia of less than 90,000/mm3 were positive. A follow-up study in cerebral malaria patients showed some variation in LALT positivity rate from day to day (85.7% on day 1, 53.3% on day 3 and all negative on discharge from hospital). LALT positivity bore no relationship to gram negative bacteraemia. Leucocytosis and elevated serum enzymes were more frequently found in LALT-positive patients. Our results suggest that endotoxin (LALT positivity) of the plasma of malaria patients is derived from either the parasites themselves or from the gut. It relates to parasitaemia, leucocytosis and elevated serum enzymes, but not to the clinical syndrome of cerebral malaria.

Bilirubin↗
PubMed1984

Multi-site intradermal and multi-site subcutaneous rabies vaccination: improved economical regimens.

Neutralising antibody responses to six post-exposure regimens of human diploid cell strain rabies vaccine with or without human rabies immune globulin (HRIG) were studied in 98 patients. The total amount of vaccine used was 22-34% of that required by conventional regimens. Vaccine was given at multiple sites intradermally or subcutaneously with or without adjuvant. Antibody was detectable within 7 days of the first dose in all subjects only in the groups given 0.1 ml intradermally at 8 sites. From day 14 onwards all groups showed an excellent antibody response; there was little difference between the various regimens. Suppression of the response to 8-site intradermal vaccination by a large dose of HRIG could be prevented by giving the second dose of vaccine on day 7 rather than day 14.

Adjuvants, Immunologic↗
PubMed1984

Failure of chloroquine-erythromycin and chloroquine-tetracycline combinations in treatment of chloroquine-resistant falciparum malaria in eastern Thailand.

In Eastern Thailand the increasing resistance of Plasmodium falciparum to all available antimalarial drugs prompted a reassessment of chloroquine in combination with either erythromycin or tetracycline. Both combinations had produced encouraging results in vitro, in experimental animal models, or in preliminary clinical trials. In patients with uncomplicated falciparum malaria presenting with moderate parasitaemia the trial of chloroquine and tetracycline was abandoned after RIII resistance with clinical deterioration was encountered in 2 out of the first 5 patients studied. Of 16 patients treated with chloroquine+erythromycin, 11 showed resistance (RI-RIII). These regimens appear ineffective and potentially dangerous in Eastern Thailand.

Adolescent↗