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Biomedical subjects

M J Warrell

Publications and source records attributed to M J Warrell.

At least 55 records · Page 3Linked 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

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

Impaired cell-mediated immunity in Plasmodium falciparum-infected patients with high-parasitemia and cerebral malaria.

Several cell-mediated functions were studied in vivo and in vitro in 63 Thai patients with acute falciparum malaria, including 21 cases with cerebral manifestations and 10 cases with initial parasitemia over 10%. Initial delayed cutaneous reactions to phytohemagglutinin and soluble protein antigens were negative in most cerebral malaria cases. In other patients, skin reactions were impaired or abolished as a direct function of parasitemia. No major alteration in the numbers of blood T and B lymphocytes was found. In lymphocyte cultures, proliferative responses to lectins were generally found within normal ranges; in contrast, proliferative responses to candidin were suppressed in parallel with delayed cutaneous responses to the same antigen. From these data, it can be concluded that the alteration of specific cell-mediated responses are predominantly detectable in acute cases with major parasite invasion, i.e., high parasitemia and/or cerebral manifestations. A direct role of Plasmodium falciparum was further suggested by the rapid restoration of cell-mediated functions observed in several cases under successful antimalarial therapy. These results do not support any evidence in favor of a preexisting cellular immune deficiency in relation with the occurrence of cerebral or high-parasitemia acute malaria in these patients.

Acute Disease↗
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↗
PubMed1983

Serum alpha-1 antichymotrypsin is a possible growth inhibitor of Plasmodium falciparum.

Serum protease inhibitors were determined in paired sera from 7 patients with cerebral malaria and 2 patients with acute malaria showing high and low growth inhibition activity in the initial and follow-up sera respectively. Alpha-1 antichymotrypsin and alpha-1 antitrypsin but not alpha-2 macroglobulin showed direct correlation with the growth inhibition activity. When alpha-1 antitrypsin was deliberately added to the malarial culture no growth inhibition occurred indicating that the alpha-1 antichymotrypsin was the most likely factor responsible for inhibition of growth of malarial parasites in vitro.

Chymotrypsin↗
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

Examination for influenza IgA and IgM antibodies in pregnancies associated with fetal neural-tube defects.

Early antenatal serum specimens were collected from 25 women who subsequently gave birth to infants with anencephaly or spina bifida. Fluorescent-antibody test for influenza-specific IgA and IgM antibodies, although shown to be reliable for the detection of recent influenzal infection, failed to demonstrate such infection in any of these women. Early infection was detected in one of 50 control women who gave birth to a healthy infant. The results indicate that influenzal infection in pregnancy was not a major cause of neural-tubal defects in Oxford during 1972--76, if a cause at all.

Antibodies, Viral↗
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↗
PubMed1980

The effects of viral infections on renal transplants and their recipients.

A prospective study of viral infections occurring after 188 renal transplants in 167 patients showed active cytomegalovirus (CMV) infection after 52 per cent of transplantations. All 37 CMV seronegative cases who received grafts from seronegative donors remained free of infection, while 24 (70.6 per cent) of 34 seronegative recipients whose donors were seropositive developed primary CMV infection (p less than 0.001). The diagnosis of 92 per cent of these primary infections was made between one and two months after grafting. Secondary CMV infection was found in 71 (62 per cent) of 114 seropositive cases, and the frequency of infection was not affected by the CMV status of the renal donor. Neither acute rejection episodes nor total graft rejections were associated with primary or secondary infections. CMV was isolated from a colonic abscess and the relationship of the virus to the intestinal disease is discussed. Herpes simplex virus was isolated from 47 per cent of cases and 32 per cent had an increase in antibody titre. Zoster was seen in nine patients, representing an incidence of 3.4 per cent per year. Other viral or mycoplasmal infections diagnosed included 71 due to respiratory tract pathogens, and a single case of hepatitis B. None of these infections was particularly severe or frequent and no association with graft rejection was detected.

Antibodies, Viral↗
PubMed1979

Mycoplasma pneumoniae and the aetiology of lobar pneumonia in northern Nigeria.

Over a six-month period we studied 74 adult Nigerians who presented consecutively to Ahmadu Bello University Teaching Hospital, Zaria, with lobar or segmental pneumonia. Pneumococcal infection was diagnosed in 50% by the detection of pneumococcal polysaccharide antigen in serum or purulent sputum: 24% had pneumococcal antigenaemia. Twelve patients had evidence of Mycoplasma pneumoniae infection and half of these also had pneumococcal infection. The suggestion that M pneumoniae respiratory infection may predispose to serious bacterial pneumonia is discussed. The initial clinical and radiological features were similar in the pneumococcal and M pneumoniae groups. Raised cold agglutinin titres were not a reliable indication of M pneumoniae infection, perhaps due to altered autoantibody production in Nigerians. Pneumonia was commoner in the dry season, probably related to depressed nasopharyngeal defences caused by drying. Less common causes of lobar pneumonia that were found are also discussed and no cases of legionnaires' disease were identified.

Adult↗
PubMedDate not supplied

Human rabies and its prevention: an overview.

Human rabies is underreported, but it clearly is still a frequent medical problem that is virtually confined to tropical countries. Rabies encephalitis remains essentially incurable, and most patients die at home, their terrible symptoms unpalliated by sedatives or analgesics. Recent attempts to cure rabies in well-equipped intensive care units have failed, a situation reemphasizing the importance of preventive measures. The great advances that have been made in understanding the rabies virus and the associated improvements in rabies vaccines have had little or no impact in the tropical endemic zone. Most patients who have been exposed to rabies are still given nervous tissue vaccines for postexposure prophylaxis. An urgent priority is the development of a regimen using tissue culture vaccine that is sufficiently economical to replace nervous tissue vaccine. This has been achieved in China with primary hamster kidney cell vaccine.

Encephalitis↗