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Biomedical subjects

D Brewster

Publications and source records attributed to D Brewster.

At least 55 records · Page 3Linked to original sources

Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies.

Plasmodium falciparum isolates from 24 Gambian children with cerebral malaria and 57 children with mild forms of the disease were assessed for their ability to form erythrocyte rosettes. All isolates from the children with cerebral malaria were able to form rosettes, whereas those from children with mild forms of the disease did not form rosettes, or had a significantly lower rosetting rate. Plasma of children with cerebral malaria lacked anti-rosetting activity, whereas plasma of children with mild disease could often disrupt rosettes in vitro. A monoclonal antibody to P falciparum histidine rich protein (PfHRP1/KP/KAHRP) disrupted rosettes of many of the isolates in vitro indicating that the rosetting ligand is relatively conserved compared with ligands associated with endothelial cytoadherence. The findings strongly support the hypothesis that erythrocyte rosetting contributes to the pathogenesis of cerebral malaria and suggest that anti-rosetting antibodies protect against cerebral disease.

Acute Disease↗

AIDS following mother-to-child transmission of HIV-2.

Mother-to-child infection with HIV-2 is thought to be rare, and there have been few previous reports of transmission by this route. Reports of morbidity associated with HIV-2 infection in children are also rare. We describe eight children born to mothers who were infected with HIV-2; five developed AIDS, and three were still seropositive at 17-49 months of age. The only apparent route of HIV-2 transmission was from mother to child, except for one child who had been transfused. Three of the children with AIDS died, all having decreased CD4+ lymphocytes and mitogen responses. Further studies are needed to determine the prevalence and natural history of mother-to-child transmission of HIV-2.

Acquired Immunodeficiency Syndrome↗

Open comparison of intramuscular chloroquine and quinine in children with severe chloroquine-sensitive falciparum malaria.

An open paired randomised comparison of intramuscular chloroquine (3.5 mg base/kg every 6 h) and intramuscular quinine (20 mg salt/kg followed by 10 mg/kg every 12 h) was carried out in 50 Gambian children with severe falciparum malaria. 8 children died, 6 from the quinine-treated and 2 from the chloroquine-treated group. Chloroquine reduced parasitaemia significantly more rapidly than did quinine, but other measures of the therapeutic response were similar in the two groups. Quinine injections were painful. These findings do not support the proposition that quinine is intrinsically superior to chloroquine in the treatment of severe drug-sensitive falciparum malaria.

Administration, Oral↗

The systemic availability of buprenorphine administered by nasal spray.

The kinetics and systemic bioavailability of intranasally administered buprenorphine have been investigated in 9 healthy volunteers in an intranasal/intravenous cross-over study. Each subject received a nominal 0.3 mg dose of buprenorphine intranasally followed one week later by a matched dose intravenously. For the intranasal administration mean tmax and mean Cmax were 30.6 min and 1.77 ng mL-1, respectively. Mean intranasal bioavailability was 48.2 +/- 8.35% (mean +/- s.e.m.) of the intravenous value. Intranasal administration may represent a valuable new delivery route for buprenorphine.

Administration, Intranasal↗

Herbal poisoning: a case report of a fatal yellow oleander poisoning from the Solomon Islands.

A fatal yellow oleander herbal poisoning is reported in a 2 1/2-year-old Melanesian boy, who had persistent vomiting,bradycardia caused by complete heart block, hyperkalemia and cardiac glycosides detected in his serum. This is one of the few recognized clinical pictures of illness from herbal poisoning, yet herbal poisoning in infants in some Pacific and African countries is common and has a high mortality.

Blood Pressure↗

Interpretation of pulmonary artery wedge pressure and pullback blood gas determinations during positive end-expiratory pressure ventilation and after exclusion of the bronchial circulation in the dog.

Left atrial pressure (LAP) and pulmonary artery wedge pressure (PWP) were measured at different heights during graded increases in positive end-expiratory pressure (PEEP). Six healthy anesthetized dogs were placed in lateral decubitus positions with a balloon-tipped pulmonary artery catheter inserted in each lung. PWP in the gravitationally superior lung overestimated LAP at 15 and at 20 cm H2O PEEP (p less than 0.05). PWP in the dependent lung was virtually identical to LAP at all degrees of PEEP. Wedge blood could be aspirated through the distal lumen of the pulmonary artery catheters during balloon inflation at all degrees of PEEP except for 3 attempts. PCO2 in wedge blood in both the nondependent and dependent lungs at all degrees of PEEP was consistently lower than PCO2 in arterial blood (p less than 0.05). Wedge blood was arterialized, i.e., oxygen saturation greater than 95%, in all but 4 specimens. Surgical elimination of the bronchial artery supply to the lung in 3 dogs did not affect PWP or blood gas measurements. We conclude that in this animal model: (1) the tip of a pulmonary artery catheter must be below the level of the left atrium, Zone III location, to accurately reflect LAP at high degrees of PEEP; (2) arterialization of wedge blood samples does not guarantee that PWP reflects LAP; (3) bronchial artery blood supply does not affect PWP or wedge blood gas measurements, even at high degrees of PEEP.

Animals↗

Thyrotropin-releasing hormone (TRH) analogues show enhanced CNS selectivity because of increased biological stability.

TRH exerts both endocrinological and neuropharmacological actions. Two analogues of TRH, Pyr-His-Mep . NH2 (L-trans-3-methylprolineamide) and Pyr-His-Dmp . NH2 (L-3,3-dimethylprolineamide) have been examined for their neuropharmacological and endocrinological effects. Comparisons of their ability to provoke hyperthermia in rabbits demonstrated that both analogues were more potent than TRH, but like the parent peptide had only a limited ability to cross the blood brain barrier. This conclusion was confirmed by whole body autoradiographical studies. In contrast both analogues had a similar potency to TRH with respect to the ability to provoke TSH release. It is concluded that the increased potency in neuropharmacological tests results from enhanced bioavailability to CNS sites and that a similar rationale can be used to explain the CNS selectively claimed in the literature for other analogues of TRH.

Animals↗

The systemic bioavailability of buprenorphine by various routes of administration.

The systemic bioavailability of buprenorphine has been studied in female rats following single doses (200 microgram kg-1) administered by one of six different routes. Relative to the 100% bioavailability from the intraarterial route the mean bioavailabilities were intravenous, 98%; intrarectal, 54%; intrahepatoportal, 49%; sublingual, 13%; and intraduodenal, 9.7%. Area under the curve analysis of buprenorphine concentrations in blood showed the relative fractions of drug extracted (first pass) by gut, liver and lung to be 0.80, 0.50 and 0.02 respectively, In situ absorption studies showed that the poor availability of intraduodenally administered buprenorphine is not due to slow or incomplete absorption.

Animals↗

Biliary excretion, metabolism and enterohepatic circulation of buprenorphine.

1. After intramuscular administration of [3H]buprenorphine to rats, dogs, rhesus monkeys and one human volunteer, most of the dosed radioactivity was excreted in the faeces, indicating biliary excretion and a possible enterohepatic circulation of the drug in these species. 2. After intravenous administration of [3H]buprenorphine (100 microgram/kg) to bile-duct cannulated rats, over 90% of the administered radioactivity was excreted in bile within 48 h after dosing. 3. The major drug-related component in rat bile was buprenorphine glucuronide. N-Dealkylated buprenorphine (again conjugated) was also present and a sex difference in the extent of N-dealkylation was apparent. 4. Intraduodenal infusion of rats with bile from rats dosed with [3H]buprenorphine produced a slow, although extensive, excretion of drug-related material in the bile of the recipient animals.

Animals↗

Modification of the proline residue of TRH enhances biological activity and inhibits degradation.

An analogue of TRH with a modified proline residue (Pyr-His-MepNH2) has been synthesised and evaluated. In CNS, but not endocrine tests the analogue had improved activity compared to TRH and was more resistant to enzymatic degradation. A metabolite of TRH, His-Pro, was without biological activity. It is concluded that the biological actions attributed to TRH are due to the parent tripeptide rather than His-Pro and that these actions can be enhanced by improving the biological stability of TRH.

Animals↗