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G Forrest

Publications and source records attributed to G Forrest.

46 records · Page 3Linked to original sources

Hepatic enzyme induction and leucocyte delta-aminolaevulinic acid synthase activity: studies with carbamazepine.

Antipyrine metabolism, daily urinary 6-beta-hydroxycortisol excretion, carbamazepine (CBZ) half-lives and leucocyte delta-aminolaevulinic acid synthase (ALA.S) activities were measured following 2 weeks' treatment with CBZ 400 mg and 600 mg once daily in eight healthy male volunteers. Dose-dependent induction of antipyrine metabolism was demonstrated but cortisol hydroxylation appeared maximally induced by the 400 mg dose. CBZ half-lives fell significantly in both studies (P less than 0.01 in each case) but a greater fall was seen with the higher dose (P less than 0.01). Plasma CBZ concentrations were higher following the eighth doses (P less than 0.01) in both studies. Leucocyte ALA.S activity increased by a mean of 657% following 1 week's treatment with 400 mg CBZ and 1145% on the 600 mg dose. In both studies ALA.S activities fell towards baseline during the second week of treatment. CBZ possesses potent dose-dependent hetero- and auto-inducing properties. Leucocyte ALA.S activity may represent a novel in vivo index of extrahepatic enzyme induction in man.

5-Aminolevulinate Synthetase↗

Prolonged outbreak of nosocomial urinary tract infection with a single strain of Pseudomonas aeruginosa.

Sixty-six hospitalized patients became infected with a single strain of multiply resistant Pseudomonas aeruginosa over a 22-month period. The catheterized urinary tract was the site of the infection in 59 patients (89%). The outbreak was confined to a urology ward until an infected patient from this ward spent 2 weeks in the surgical intensive care unit (SICU). Subsequently patients who acquired the infection in the SICU were discharged to surgical wards throughout the hospital. Urine measuring containers and urometers used in the SICU were the reservoir of the P. aeruginosa; daily sterilization of this equipment terminated the outbreak. Urometers appeared to be the reservoir of the epidemic strain in subsequent outbreaks. Five patients were still infected when they were readmitted 3 to 12 months after the first admission, and therefore represented an additional reservoir of infection.

Cross Infection↗

Cholera-like diarrhea in Canada. Report of a case associated with enterotoxigenic Escherichia coli and a toxin-producing Aeromonas hydrophila.

A 67-year-old Indian patient was admitted with an acute cholera-like illness. Toxigenic Escherichia coli producing both heat-stable and heat-labile enterotoxins grew from cultures of feces. In addition, an Aeromonas hydrophila producing a cytotoxic toxin was also isolated from this patient's feces. The unusual severity of this patient's illness may have resulted from coinfection with these two toxigenic organisms, although any role of the toxin produced by a hydrophila is speculative.

Aeromonas↗

Isolation and characterization of HL-A variants in cultured human lymphoid cells.

We have developed a procedure for immune selection in an established human lymphoid cell line based on HL-A, the major human histocompatibility locus. After a single brief exposure to selective conditions, HL-A2 variant clones were isolated from an HL-A2/HL-A3 heterozygous line. The variant clones occurred at a frequency of about 1 x 10(-6). The variant phenotype was stable during prolonged growth in the absence of antiserum after isolation. The variant sublines bound [unk] 1/1000 the HL-A2 antibody per cell as the parent line. Variation was specific in that expression of antigens not selected against was unimpaired. Loss of the chromosome bearing HL-A2 was excluded as the cause of variation because the variants, like the parent line, were heterozygous for phosphoglucomutase (EC 2.7.5.1) determined by structural locus PGM(3), which is linked to HL-A.

Animals↗

Dihydropyridine calcium antagonists in mice: blood and brain pharmacokinetics and efficacy against pentylenetetrazol seizures.

Dihydropyridine calcium antagonists are candidate anticonvulsants, but little is known of their penetration into brain. Nifedipine (NFD) and nimodipine (NMD) pharmacokinetics were compared in mouse blood and brain, and their activity against pentylenetetrazol (PTZ) was assessed. After intraperitoneal (i.p.) injection, both dihydropyridines achieved peak blood and brain concentrations in 5 min. Estimated blood and brain elimination half-lives (t1/2) of NMD (16.7 and 22.4 min) were slightly longer than those of NFD (11.2 and 14.7 min). Brain and blood concentrations correlated with both NFD (r = 0.701, p less than 0.001) and NMD (r = 0.572, p less than 0.001). Injection of the dihydropyridines as a suspension (Tween 80) did not alter brain penetration, although systemic absorption was more erratic. NFD (p less than 0.001), NMD (p less than 0.02), and carbamazepine (CBZ, p less than 0.001) i.p. inhibited PTZ-induced seizures. Brain concentrations of PTZ were not altered by NFD pretreatment. Combining NFD and CBZ was less effective than giving NFD alone (p less than 0.005). NFD (p less than 0.002) and NMD (p less than 0.001) inhibited PTZ seizures after 2-week oral dosing, but low dosing was more effective than high dosing (p less than 0.002). NFD and NMD cross the blood-brain barrier (BBB) in mice and inhibit PTZ seizures. A possible therapeutic window was identified, and NFD and CBZ were less effective in combination than singly. A pharmacodynamic interaction may exist, inhibiting effective use of dihydropyridines as adjunctive therapy in epileptic patients.

Animals↗

The reality game.

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Adult↗