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Biomedical subjects

J F Douglas

Publications and source records attributed to J F Douglas.

At least 73 records · Page 4Linked to original sources

Isotope renography and long term follow-up of renal transplant patients.

Isotope renography was carried out in 64 kidney transplant patients attending a follow-up clinic. Graft survival in these patients ranged from two months to ten years. Forty-one patients had normal renograms and 98% of these had satisfactory function (creatinine clearance greater than 50 ml/min). Eighteen patients showed a major renogram abnormality and 50% of these had impaired function. Five of these 18 have been explored and found to have graft complications (obstructive disease in four, chronic pyelonephritis in one). Exploration has not been undertaken in the remaining 13 but nine show evidence suggestive of graft pathology (proteinuria, impaired creatinine clearance, elevated urinary enzymes, calyceal distortion on IVP). A successful kidney transplant should result in a normal isotope renogram, and a major abnormality of the renogram suggests the presence of a graft complication, even when the creatinine clearance is unimpaired. We feel renography is useful for identification of renal transplant patients who require further investigation or closer follow-up.

Creatinine↗

Determination of anthranilic acid in plasma.

A simple, specific GLC method was developed for the determination of anthranilic acid in plasma. This method is based on extraction from a carefully controlled buffer followed by removal of solvent, silyation, and detection in the gas chromatograph. The procedure is quantitative in the 2-10 microgram/ml range.

Animals↗

Absorption, distribution and metabolic fate of 2,3-dihydro-9H-isoxazolo-[3,2-b]quinazolin-9-one (W2429).

After oral administration to rats, mice, beagle dogs and human volunteers, 2,3-dihydro-9H-isoxazolo [3,2-b]-quinazolin-9-one (W 2429) is readily absorbed. The initial half-lives for the elimination from the circulation of these four species are about 240, 20, 40 and 120 min, respectively. Studies in the rat, using 9-14C-W-2429 and 3a-14C-W-2429, showed that more than half of the radioactivity is excreted in the urine. The major urinary metabolite in the rat and dog is a conjugated form of W-2429. Metabolic cleavage of the pyrimidone ring of W-2429 yields 3-(o-carboxyphenylimino)isoxazolidine, which in turn is converted to anthranilic and malonic acids. Anthranilic acid is acetylated and hydroxylated, and these products are excreted partly in the form of their glycine and glucuronic acid conjugates. The isoxazole ring of W-2429 is also dehydrogenated during metabolism to yield 9H-isoxanzolo-[3,2-b]quinazolin-9-one.

Administration, Oral↗

Treatment of peptic ulcer in renal failure.

The occurrence and pathophysiology of peptic ulcer was studied in 117 uraemic patients. Ulcer disease was unusually frequent, and the highest incidence was found in patients on regular dialysis (48%). Factors implicated were hyperacidity, hypergastrinaemia, and the effect of dialysis itself. We found that the occurrence of gastrointestinal bleeding was lower post-transplant (7%), than pre-transplant (15%), and that bleeding in renal transplant patients was due more commonly to erosive gastritis than peptic ulcer. Cimetidene was given to 9 regular dialysis patients with peptic ulcer. Symptomatic relief and significant reduction of acid secretion was demonstrated, and no major side effects occured. There is a logical basis for conservative treatment of uncomplicated peptic ulcer in the dialysis patient, and further evaluation of cimetidene is indicated.

Cimetidine↗

Effect of concurrent administration of aspirin, indomethacin or hydrocortisone with gold sodium thiomalate against adjuvant-induced arthritis in the rat.

The activity of gold sodium thiomalate (GST) given i.m. to adjuvant-induced polyarthritic rats was studied alone or in combination with active doses of aspirin, indomethacin and hydrocortisone. In addition to paw volume and body weight changes, erythrocyte sedimentation rate, serum albumin/globulin and gold levels as well as plasma activities of beta-glucuronidase, acid phosphatase, lysozyme and lactic acid dehydrogenase were measured. In prophylactic studies the beneficial activity of GST was unaffected by aspirin, suggesting a positive drug interaction, but additive with indomethacin or hydrocortisone for the 1st but not 2nd lesion of the disease. These results were closely correlated with increased serum gold levels. Similar clinical findings were observed in therapeutic studies except that a positive drug interaction occurred between GST and hydrocortisone. Unlike in the prophylactic experiments, serum gold levels were unaffected by any of the agents tested in the therapeutic studies.

Animals↗

Absorption, distribution, and metabolic fate of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one in rats, dogs, and humans.

The absorption and metabolic fate of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one (I) was studied in rats, dogs, and humans. Orally administered I was readily absorbed by all species. In the rat, orally administered I was converted to its metabolite, 5-chlorosalicylic acid, by the intestinal wall. The half-lives of blood radioactivity, after the oral administration of I-9-14C, were about 18 and 12 hr in the rat and beagle hound, respectively. In human subjects, no intact I was detected in the bloodstream; however, the clearance of the metabolite, 5-chlorosalicylic acid, had a half-life of about 33 hr. Cleavage of the oxazine ring of I generated 5-chlorosalicylic acid, which was excreted both in the free form and conjugated with glycine and glucuronic acid. The isoxazole moiety was converted to beta-hydroxybutyric acid and its metabolites carbon dioxide and fumaric, citric, alpha-ketoglutaric, succinic, and malic acids. Binding of I to plasma proteins was extensive but was less than that of 5-chlorosalicylic acid.

Animals↗

Comparison of the lipopretein profiles and the effect of N-phenylpropyl-N-benzyloxy acetamide in primates (38473).

Analytical ultracentrifugation showed Cebus and Rhesus monkeys had two low density components while only one was present in Squirrel monkeys. In untreated or W1372 treated monkeys, neither chylomicrons nor very low density lipoproteins were detected on analytical ultracentrifugation. Chylomicrons were not observed on agarose gel electrophoresis. Ultracentrifugal analysis showed W1372 treatment decreased the amount of LDL in all animals and also the HDL in Cebus monkeys on an atherogenic diet. Both untreated and W1372 treated Cebus monkeys on an atherogenic diet had abnormal amounts of LDL and HDL, while the LDL in treated animals occurred as multiple peaks. This was also evident on agarose gel electrophoresis. Accumulation of lipds in the liver and decrease of serum lipids indicated W1372 prevented release of lipoproteins from the liver.

Acetamides↗