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Biomedical subjects

J R Brooks

Publications and source records attributed to J R Brooks.

10 recordsLinked to original sources
PubMed1991

Topical anti-androgenicity of a new 4-azasteroid in the hamster.

The topical anti-androgenic activity of L-651,580 (methyl 3-oxo-4-methyl-4-aza-5 alpha-androst-1-ene-17 beta-carboxylate) was established in a series of for experiments using castrated male hamsters. During each 21-day experiment, the animals received a daily subcutaneous injection of 40 micrograms testosterone propionate or 20 micrograms dihydrotestosterone propionate. Test compound in 25 microliters of gel was applied daily to the left flank organ. Compounds assayed included L-651,580, WIN 17,665 (17 alpha-propyltestosterone), and SH-434 (17 beta-hydroxy-1 alpha-methyl-17 alpha-propyl-5 alpha-androstan-3-one). Endpoints were flank organ area, sebaceous gland area, and prostate weight. Very similar results were obtained with L-651,580 and WIN 17,665. Daily doses of 0.25 mg or more of either compound usually produced a significant reduction in the areas of treated flank organs and sebaceous glands underlying treated flank organs. Neither compound caused significant changes in the area of the contralateral flank organs and sebaceous glands, which indicated they possess little or no systemic activity at topically effective treatment levels. In direct comparisons, SH-434 was less anti-androgenic than L-651,580 or WIN 17,665, although in one experiment, 0.5 mg/d of SH-434 significantly reduced the area of treated flank organs and sebaceous glands. Neither WIN 17,665 nor SH-434 caused a change in prostate weight; however, in one of four tests, a significant decrease was induced by the 0.5 mg/d level of L-651,580. The results of these experiments show that the topical anti-androgenicity of L-651,580 compares very favorably with that of WIN 17,665 and SH-434. They also indicate that the topical administration of effective dosage levels of L-651,580 causes few, if any, systemic effects.

Administration, Topical↗
PubMed1979

Lethal pancreatitis: a diagnostic dilemma.

Clinical and pathological information from forty patients who died with pathologically severe acute pancreatitis was correlated. Patients were classified into four etiologic groups: those with biliary pancreatitis (11 patients), alcoholic pancreatitis (13 patients), idiopathic pancreatitis (10 patients), and renal failure (6 patients). Antemortem diagnosis was made in only 57 per cent of the patients studied. The diagnosis was determined before death in 91 per cent of the biliary patients but in none of the renal patients. Thirty-seven patients died from their first clinical attack of pancreatitis. Operation in patients with biliary pancreatitis failed when biliary decompression was not provided. Peripancreatic sepsis was a frequent lethal mechanism in patients with biliary pancreatitis, but renal and respiratory failure were more common in patients with alcoholic pancreatitis.

Acute Disease↗
PubMed1979

Histopathology in the evaluation of total pancreatectomy for ductal carcinoma.

Whipple resections for pancreatic head carcinoma are often inadequate because tumor is left behind in the body and tail. Thirty-six patients have undergone total pancreatectomy for various conditions, of which 25 have undergone total pancreatectomy, for ductal carcinoma. Thirty-seven per cent of these 25 patients have shown histologic evidence that a Whipple resection would not have adequately removed tumor-bearing pancreatic tissue. Three patients had carcinoma spreading up and along the common bile duct from a primary ductal carcinoma in the head of the pancreas. Four patients had tumor infiltrating in continuity into the pancreatic body and tail at a distance from the palpable tumore in the head well to the left of a Whipple transection site. Five patients had widespread multifocal autonomous tumor involving other areas in the gland but with tumor palpable only in the head of the pancreas. Three patients (12%) died postoperatively. The two year survival rate is 32%, and the five year survival, 19%. Histological factors affecting the survival prognosis include 1) positive nodes, 2) tumor extension up the common duct, and 3) intrapancreatic extension and multicentricity of tumor mandating total pancreatectomy for hope of cure in at least 38% of cases.

Humans↗
PubMed1979

Operative approach to pancreatic carcinoma.

It is apparent that we are dealing with a very lethal disease. It is also apparent that this disease is increasing in frequency. In terms of treatment, it is clear that the survival figures between carcinoma of the pancreas and carcinoma of the common duct, papilla of Vater, or duodenum present great differences. The pancreatic tumors do very poorly by comparison. A comparison of the survival figures following a Whipple resection and following a bypass procedure reveal similar results, except when dealing with a very small pancreatic head lesion or when dealing with a malignancy of the papilla of Vater, lower end of common duct, or duodenum. The latter tumor types do better with a Whipple resection than a bypass. A comparison between total pancreatectomy and a Whipple resection for ductal carcinoma of the pancreatic head reveals better results in terms of length of survival following total pancreatectomy as long as one considers only Stage I or Stage II disease and excludes Stage III disease. A Whipple procedure is advocated for carcinoma of the papilla of Vater, common duct, or duodenum, because survival figures are quite good and many patients escape the need for insulin and pancreatic extract replacement. It is too early to evaluate the survival figures that follow regional pancreatectomy.

Ampulla of Vater↗
PubMed1978

pH-tested reflux without hiatus hernia.

Gastroesophageal reflux was tested for with a pH telemetry capsule. In 29 individuals in whom no hiatus hernia was demonstrated on barium esophagram, the transverse diameter of the intrahiatal esophagus was compared to that of the intrathoracic. When the width of the intrahiatal esophagus was two-thirds or less that of the intrathoracic, pH-proven reflux was an infrequent event. When wider, reflux occurred with high frequency.

Gastric Acidity Determination↗
PubMed1977

Biological spectrum of two spirolactone derivatives with some observations on anti-fertility activity.

Bioassays were conducted to determine various endocrinological properties of two spirolactone derivatives, 4',5'-dihydrospiro-[estr-4-ene-17,2'(3'H)-furan]-3-one (Compound I) and dispiro[cyclopropane-1,6'-estr-4'-ene-17',2"(3"h)-furan]-3'-one (Compound II). They proved to be very potent estrogen antagonists in immature mice and castrate ewes and neither exhibited inherent estrogenicity. They were moderately active as progestins and gonadotropin inhibitors. Compound II possessed slight androgenic activity and was more active orally than I. Compound I underwent a limited amount of testing in normally cycling rhesus monkeys. It was found to increase viscosity of the cervical mucus and, in oral doses of 0.5 or 2.0 mg/day, prevented pregnancy. One animal given 0.5 mg/day did become pregnant in her first treatment cycle, probably before a drug effect had been established. The results obtained indicate both compounds have potential utility as low-dose oral contraceptives.

Androgens↗
PubMed1976

Cancer of the pancreas. Palliative operation, Whipple procedure, or total pancreatectomy?

The choice of operation for ductal carcinoma of the pancreas is as yet not clear. Failure to make an early diagnosis still stands out as the major problem in the treatment of this disease and as a result the resectability rate is exceedingly low. Between 1964 and 1973, nineteen total pancreatectomies were performed at Peter Bent Brigham Hospital for all tumors of the pancreas. Sixteen of these were for ductal carcinoma. The mortality was 12.5 per cent. When total pancreatectomy is compared with the Whipple procedure and a simple bypass procedure and when the tumor disease encountered is corrected for stage of disease, it is apparent that total pancreatectomy carries a statistically significant longer survival for patients with Stages I and II disease (no lymph node involvement) than the other two procedures. For Stages III and IV, there is no difference in survival between the three different operations. We therefore conclude that total pancreatectomy carries a better survival prognosis than other procedures performed for Stage I and II ductal carcinoma of the pancreas.

Adult↗
PubMed1975

Truncal vagotomy and pyloroplasty for duodenal ulcer.

Two hundred sixty-five patients who underwent vagotomy and pyloroplasty for duodenal ulcer disease were observed postoperatively, 220 for two to ten years, with an average follow-up of five years. Vagotomy and pyloroplasty carried a higher overall recurrence rate (3.6%) than did subtotal gastrectomy and vagotomy (1%), largely because of the high ulcer recurrence rate more than two years after operation for massive bleeding (9.2%) rather than that following elective operation (1.8%). Thirty-five percent of these patients with recurrent ulcers did well with medical management and did not require a second operation. The mortality of vagotomy and pyloroplasty for a massively bleeding ulcer (11%) was less than that following subtotal gastrectomy (21%). The mortality of elective vagotomy and pyloroplasty was 1%.

Adult↗