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Biomedical subjects

D Brewster

Publications and source records attributed to D Brewster.

69 records · Page 4Linked to original sources
PubMed1980

Valproate plasma protein binding in the uremic condition.

The protein binding of sodium [carboxy-14C] valproate has been studied in normal and uremic plasma using the method of equilibrium dialysis. Protein binding was dependent on concentration in both cases but there was a marked reduction in binding capacity in patients with renal dysfunction. Treatment of normal plasma with urea or creatinine to reproduce concentrations observed in uremia induced small decreases in binding. Diffusion dialysis of uremic plasma partially restored the degree of binding. Pretreatment of uremic plasma with activated charcoal at pH 3 raised binding capacity to that of normal plasma.

Blood Proteins↗
PubMed1979

Mass spectrometry in the elucidation of shikimate biotransformation products in the rat.

The biotransformation products of shikimate in the rat have been identified by electron impact mass spectrometry. Analysis of the metabolites produced after oral administration of shikimate resulted in the identification of hippurate, 3,4,5,6-tetrahydrohippurate, hexahydrohippurate, benzoyl and cyclohexylcarbonyl-beta-D-glucuronides and two isomeric 3,4-dihydroxycyclohexanecarboxylates. Results showed that shikimate itself is not metabolized by rat tissues and that all metabolites produced were dependent upon initial metabolic transformations by gastrointestinal microrganisms. The various hippurate derivatives and glucuronide conjugates appear to arise via a conversion of shikimate to cyclohexanecarboxylate, which is then further metabolized by the rat tissues.

Animals↗
PubMed1978

The metabolism of shikimate in the rat.

In the rat, shikimate was metabolized and excreted as hippurate, hexahydrohippurate, 3,4,5,6-tetrahydrohippurate, t-3,t-4-dihydroxycyclohexane-r-1-carboxylate and c-3,t-4-dihydroxycyclophexane-r-1-carboxylate, conjugates of catechol and CO2. The metabolism was entirely dependent on various initial microbial transformations in the gut, metabolite formation being suppressed in animals pretreated with antibiotics. Shikimate was not metabolized by mammalian tissues, and products of microbial metabolism were excreted either unchanged or after further biotransformation in the animal tissues.

Animals↗
PubMed1977

The metabolism of cyclohexanecarboxylate in the rat.

In the rat, cyclohexanecarboxylate was metabolized and excreted (mostly in the urine) as hippurate, hexahydrohippurate, 3,4,5,6-tetrahydrohippurate and benzoyl and cyclohexylcarbonyl beta-glucuronides. The pattern of metabolism is dose-dependent. With decreasing dose a progressive increase in the conversion into hippurate occurred. This was largely at the expense of glucuronide formation, although the proportions of hexahydro- and tetrahydro-hippurate were also decreased. The observed formation of hexahydrohippurate and 3,4,5,5-tetrahydrohippurate substantiates the proposed mechanism of aromatization of cyclohexanecarboxylate. It appears that these compounds arise via glycine conjugation of active intermediates in the aromatization process. Hexahydrohippurate and 3,4,5,6-tetrahydrohippurate may occur in the urine of rats as new mitabolities of shikimate, dependent for their formation on microbial metabolism.

Animals↗
PubMed1977

The metabolism of cyclohexanecarboxylic acid in the isolated perfused rat liver.

1. Cyclohexanecarboxylic acid in isolated perfused rat livers was eliminated from the perfusion system by a first-order process. 2. After 6 h, 16% was excreted in bile as cyclohexylcarbonyl beta-D-glucuronide. The remainder was present in the perfusate as unchanged cyclohexanecarboxylic acid (10%), hippuric acid (50%), hexahydrohippuric acid (2%), 3,4,5,6-tetrahydrohippuric acid (2%), cyclohexylcarbonyl-beta-D-glucuronide (2-4%) and benzoic acid (1-2%). Six per cent of the dose was associated with the red blood cell present in the perfusion medium. 3. Unlike the whole animal, the isolated rat liver produced no detectable benzoyl glucuronide. 4. The identity and kinetics of production of the metabolites are consistent with a metabolic pathway previously proposed for cyclohexanecarboxylic acid and shikimic acid.

Animals↗
PubMedDate not supplied

The pharmacokinetic properties of intramuscular quinine in Gambian children with severe falciparum malaria.

Plasma quinine concentrations were measured in 21 Gambian children with severe falciparum malaria after intramuscular administration of a 20 mg (salt) per kg loading dose of quinine dihydrochloride followed by 10 mg/kg at 12 h intervals. Quinine was well absorbed reaching mean peak concentrations of 15.6 (standard deviation [SD] 4.5) mg/litre in a median time of 3 h (range 1-6 h). A one compartment model was fitted to the plasma concentration-time profile. The mean estimated systemic clearance (Cl/F) was 0.89 (SD 0.81) ml/kg/min and the mean elimination half life was 18.8 (SD 8.0) h. Two patients, one of whom died, had low plasma quinine levels which remained below 10 mg/litre. Mean peak and trough plasma concentrations after subsequent intramuscular doses ranged between 11.1 and 15.1 mg/litre. In most cases this dose regimen provided a satisfactory profile of blood concentrations for the treatment of severe malaria in children.

Animals↗
PubMedDate not supplied

Intracranial pressure in childhood cerebral malaria.

Lumbar punctures were performed in 40 Gambian children with acute cerebral malaria aged between 18 months and 10 years. The mean opening pressure was elevated in 32 (80%) of the children, but was not significantly different in the 14 fatal cases compared with survivors: 110 (standard deviation 71) versus 131 (58) mm of cerebrospinal fluid respectively. Cerebral perfusion pressures were also similar in the 2 groups: 64 (20) mm Hg versus 64 (11) mm Hg respectively. There was no clear clinical evidence of raised intracranial pressure, and no evidence of deterioration immediately following lumbar puncture. Nevertheless brain swelling, and consequent brain-stem compression, may contribute to a fatal outcome in cerebral malaria--particularly in those children who die from sudden respiratory arrest. A prospective evaluation of osmotic agents in childhood cerebral malaria seems to be justified.

Child↗
PubMedDate not supplied

Lactic acidosis and hypoglycaemia in children with severe malaria: pathophysiological and prognostic significance.

Serial clinical and metabolic changes were monitored in 115 Gambian children (1.5-12 years old) with severe malaria. Fifty-three children (46%) had cerebral malaria (coma score < or = 2) and 21 (18%) died. Admission geometric mean venous blood lactate concentrations were almost twice as high in fatal cases as in survivors (7.1 mmol/L vs. 3.6 mmol/L; P < 0.001) and were correlated with levels of tumour necrosis factor (r = 0.42, n = 79; P < 0.0001) and interleukin 1-alpha (r = 0.6, n = 34; P < 0.0001). Admission blood venous glucose concentrations were lower in fatal cases than survivors (3.2 mmol/L, vs. 5.8 mmol/L; P < 0.0001). Treatment with quinine was associated with significantly more episodes of post-admission hypoglycaemia when compared with artemether or chloroquine. After treatment, lactate concentrations fell rapidly in survivors but fell only slightly, or rose, in fatal cases. Plasma cytokine levels fluctuated widely after admission. Sustained hyperlactataemia (raised lactate concentrations, 4 h after admission) proved to be the best overall prognostic indicator of outcome in this series. Lactic acidosis is an important cause of death in severe malaria.

Acidosis, Lactic↗
PubMedDate not supplied

Electrocardiographic monitoring in severe falciparum malaria.

Electrocardiographic monitoring over 24 h was performed with 53 patients with severe Plasmodium falciparum malaria (11 adults and 42 children) to assess the frequency of unrecognized cardiac arrhythmias. Nine patients (17%) died, 5 during the monitoring period and 4 afterwards. Pauses lasting 2-3 s were observed in 3 children, a single couplet in one, and a further child experienced frequent supraventricular ectopic beats which had not been detected clinically. In none of the patients who died could death be attributed to cardiac arrhythmia. Furthermore, no abnormality was detected which could have resulted from the often large doses of quinine, chloroquine or the artemisinin derivatives used for treatment. These results suggest that the heart is remarkably resilient even in the face of heavy parasite sequestration and other vital organ dysfunction, and that deaths from cardiac arrhythmias in severe malaria are rare. The need for routine cardiac monitoring of patients with severe and complicated P. falciparum malaria is questionable.

Adolescent↗
PubMedDate not supplied

Spontaneous perforation of common bile duct.

A 2-week-old Micronesian infant presented with spontaneous perforation of the common bile duct. Mild jaundice, acholic stools, and heavily bile-stained ascites were the main clinical features. The presentation of this rare disorder is characteristic enough to permit early diagnosis. Surgery is the treatment of choice.

Ascitic Fluid↗