Hypoglycaemia is an important complication of falciparum malaria.
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Animals↗
Biomedical subjects
R E Phillips
Publications and source records attributed to R E Phillips.
Enzymatic amplification of exogenous and endogenous retroviral sequences from DNA of patients with tropical spastic paraparesis.
Using oligonucleotide primers that hybridize to conserved sequences in the reverse transcriptase (RT) gene, we have amplified by the polymerase chain reaction three sequence variants of HTLV-I from the genomic DNA of five patients with tropical spastic paraparesis (TSP), and a fourth sequence variant from a healthy carrier of HTLV-I. These results unequivocally identify the retrovirus associated with TSP as HTLV-I and suggest that no sequence variant is uniquely responsible for the condition. The same primers served to amplify two novel single-copy endogenous retroviral RT sequences related to the exogenous mammalian leukaemia viruses: and three KpnI (LINE1) family DNA repeats. This strategy, combining the sensitivity of PCR with cross-reactive primers, may be useful in the search for known or novel retroviruses in other diseases of possible retroviral aetiology.
Amino Acid Sequence↗
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↗
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↗
Involvement of serotonin in prolactin release induced by electrical stimulation of the hypothalamus of the turkey (Meleagris gallopavo).
In anesthetized female turkeys electrical stimulation of the ventromedial nucleus (VMN) for 30 min caused increases in plasma prolactin (Prl); with maximum increase above the prestimulation level being 33.6 +/- 5.7 ng/ml for laying hens and 768.1 +/- 187.6 ng/ml for incubating hens. The possibility that serotonin (5-HT) plays a role in electrical stimulation-induced Prl release was investigated after administration of methysergide, a 5-HT receptor blocker (20 mg/kg), and stimulation in either the VMN or the infundibular nuclear complex-median eminence (INF-ME) region. Electrical stimulation in both the VMN and INF-ME region caused increases (P less than 0.05) in plasma Prl. Pretreatment with methysergide prevented the increase in plasma Prl that follows electrical stimulation in the VMN but had no effect on electrical stimulation-induced Prl release in the INF-ME region. We conclude that Prl release in the female turkey requires the functional integrity of serotonergic neurons within the VMN.
Animals↗
Altered uptake of metronidazole in vitro by stocks of Giardia intestinalis with different drug sensitivities.
Growth of Giardia intestinalis in TYI-S-33 medium containing a sub-lethal concentration of metronidazole over a period of 66 weeks selected a line of organisms that was over 8 times less sensitive to the drug. This resistance was unstable and the organisms reverted to their original sensitivity within 22 weeks of growth in the absence of drug. A comparison of the uptake of [14C]metronidazole by the original and selected lines showed a highly significant reduction in drug uptake by the resistant line, indicating either a defective transport mechanism across the cell membrane or decreased reduction of metronidazole to the active metabolite within the cell. There was no significant difference in the uptake of metronidazole by 9 recent isolates of G. intestinalis maintained in axenic culture.
Animals↗
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↗
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↗
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↗
Ionic interactions of polyurethanes.
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Animals↗
Biomedical applications of polyurethanes: implications of failure mechanisms.
Three mechanisms have been described which explain various observed interactions between polyurethane chemistry and body chemistry. These include calcification, environmental stress cracking, and chain scission. Each may result in implant device failure, and each appears to involve metal ion complexation as a key parameter. Continued expansion of polyurethane into implantable product applications will require further clarification of the effect of each of these interactions on long-term product performance. It is believed that design considerations and polymer modifications will help control the effects of each of the interactions and will result in new and improved polyurethane implant products.
Biocompatible Materials↗
The creative moment: improvising in jazz and psychotherapy.
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Adolescent↗
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↗
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↗
Studies of poly(ether)urethane pacemaker lead insulation oxidation.
Published reports suggest that silver ions may catalyze the oxidation of poly(ether)urethane soft-segments resulting in the failure of urethane insulations of specific models of pacemaker leads. Attempted oxidation of soft-segment models, poly(tetra-methylene ether)glycols, by silver nitrate has shown that metal-ion catalyzed oxidative-reduction (MICOR) does not adequately explain observed failures unless antioxidants are removed in process. Such cracking can, however, be explained in terms of a metal ion enhanced environmental stress cracking.
Biocompatible Materials↗
Prolactin release following electrical stimulation of the brain in female turkeys (Meleagris gallopavo).
Different regions of the hypothalamus were electrically stimulated in anesthetized adult female turkeys. Plasma levels of prolactin (Prl) were measured before (-20, 0 min), during (5, 10, 20, 30 min), and after (5, 15, 30, 60, 90 min) a 30-min period of electrical stimulation. In turkeys with electrode placements in the regions of the preoptic-anterior hypothalamus, ventromedial hypothalamus, inferior hypothalamus, and the median eminence, the onset of stimulation increased plasma Prl within 5 min (P less than 0.05) and the maximum level was reached by the end of the 30-min stimulation period. The termination of hypothalamic stimulation was followed by decreased plasma Prl to prestimulation levels. In a subsequent study plasma Prl was measured in hens at different stages of the reproductive cycle, following electrical stimulation in the ventromedial hypothalamus. Ventromedial stimulation induced increases in plasma Prl in laying, photorefractory, and incubating turkeys; however, the relative change in the maximal Prl level was greater in incubating (21-fold) than in either laying (3.5-fold) or photorefractory (5-fold) turkeys. We conclude that Prl release in the female turkey can be affected by electrical stimulation of selected hypothalamic areas and that stimulation-induced Prl release in the ventromedial hypothalamus is enhanced in incubating turkeys.
Animals↗
Heterogeneity in the responses of clones of Giardia intestinalis to anti-giardial drugs.
Clones of two stocks of Giardia intestinalis have been tested by the [3H]thymidine uptake assay to determine their sensitivity to metronidazole, tinidazole, furazolidone and quinacrine. Each stock was not homogeneous with respect to drug sensitivity but was composed of different populations of organisms. Doubling times of lines derived from clones of a stock did not vary significantly. These findings may, in part, account for treatment failures in human giardiasis patients.
Animals↗
Antibody response to suckling mouse brain rabies vaccines for post exposure treatment.
A new suckling mouse brain vaccine (SMBV) against rabies, produced by the Thai Red Cross Society, was compared with the well established Institut Pasteur SMBV in patients with very low risk rabies contact. The 4 regimens used were the standard daily injections with booster doses of Thai Red Cross vaccine (TRCV) and Institut Pasteur Vaccine (IPV), and a reduced dose scheme of 6 injections as used for tissue culture vaccines. The effect of 20 IU/kg of human rabies immune globulin (HRIG) was tested on each regimen, making 8 groups, a total of 122 patients. Blood samples taken on days 0, 7, 14, 28 and 91 were tested for neutralizing antibody. Only the standard IPV regimen produced antibody in every patient; all had levels greater than 0.5 IU at some stage. Two people (13%) given the standard TRCV produced no detectable antibody (less than or equal to 0.1 IU) throughout the study. The reduced dose regimens gave very low antibody levels. 7% of the IPV and 76% of the TRCV groups failed to produce antibody on any occasion. The antibody response was significantly suppressed by the administration of HRIG. Compared to the original South American SMBV, the vaccines tested induced low levels of short lived antibody. No reduction in the dosage of SMBV should be considered unless the potency of the product is adequate.
Adult↗