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Biomedical subjects

A R Moossa

Publications and source records attributed to A R Moossa.

At least 145 records · Page 8Linked to original sources

Choleresis and cholestasis produced by infusion of taurocholic acid or taurodehydrocholic acid combined with BSP in the rhesus monkey.

To study the determinants of BSP Tm in rhesus monkeys, animals with indwelling silastic catheters were infused with sufficient BSP to produce a rising plasma concentration and normal saline or taurocholic acid 3.5 mumol/min, 7.0 mumol/min, or 10.5 mumol/min. BSP Tm was 3.84 +/- 0.11 mg/kg/10 min during normal saline infusion, 5.52 +/- 0.53 mg/kg/10 min during taurocholic acid 3.5 mumol/min, despite greater bile flow with the latter compound. Higher infusion rates of taurocholic acid inhibited BSP Tm and the proportion of conjugated BSP secreted into bile, as well as bile flow and bile acid secretion. Taurodehydrocholic acid 7.0 mumol/min produced similar but less marked effects. These results indicate that bile flow does not explain the effects of bile acids on BSP Tm and suggests that bile acids exert varying effects on BSP transport or binding in micelles. The cholestasis observed with combined BSP and higher bile acid infusion rates is probably due to inhibition of liver cell intermediary metabolism or to liver cell toxicity.

Animals↗

Prospective evaluation of angiography in the diagnosis and management of patients suspected of having pancreatic cancer.

One hundred three patients suspected of having pancreatic cancer underwent celiac and superior mesenteric arteriography which was reported 'blind.' Final diagnosis, operative findings, and resectability of pancreatic cancers were correlated with angiography reports. Forty patients had pancreatic cancer. Thirty-seven of these underwent laparotomy, and 14 (37%) had resectable lesions. Sensitivity and specificity of arteriogrphy for pancreatic cancer were 72% (29/40) and 71% (45/63) respectively. Resectability was unrelated to the angiographic diagnosis. Nonresectability was related to an angiographic finding of definite tumor vessel (4/4), large-vessel encasement (14/7), and major venous pathology (8/11). Only the first of these was unique to pancreatic cancer. Hepatic metastases were detected in only six of 13 patients. Small-artery encasement, arterial occlusion, vessel displacement, and gallbladder distention were not indicators of diagnosis or extent of disease. Major anatomic anomaly of foregut vasulature was revealed in 25% of angiographic studies. Prior knowledge of such anomalies has important bearing on the operative approach to pancreatic resection. We conclude that angiography should be performed prior to laparotomy whenever a resectable pancreatic cancer is suspected from other investigations. When used prospectively, angiography is not a reliable diagnostic or prognostic tool for pancreatic cancer.

Adolescent↗

Sodium taurocholate modifies the bile acid-independent fraction of canalicular bile flow in the rhesus monkey.

Bile acid-independent secretion and the choleretic response to taurocholate were determined in rhesus monkeys fitted with indwelling silastic cannulas in the common bile ducts. Bile acids were infused intravenously in random order at 3.5, 7.0, or 10.5 mumol/min for 1.5 h each. When data were analyzed with a single regression line, bile flow increased in proportion to the level of bile acid secretion, although the y-intercepts (the conventional measurement of bile acid-independent secretion) varied widely (77.9+/-40.9 ml/24 h). The variation in y-intercepts was observed between animals and with repeated studies in the same animal and could not be explained by sex differences or the effects of the indwelling silastic cannulas, but seemed to be related to the order of bile acid infusion. With only two taurocholic acid infusion rates (7.0 and 3.5 mumol/min), [(14)C]erythritol clearance was greater per mole of secreted bile acid when the initial bile acid infusion was at the high level, but approached zero at low bile acid secretion rates, which suggests that so-called bile acid-independent canalicular flow is closely related to bile acid secretion or is small in size. The augmentation in [(14)C]erythritol clearance when the high infusion rate was given first was also associated with an increase in biliary clearance of [(3)H]inulin, which indicates that the premeability to inulin was also enhanced. Identical experiments which substituted equimolar infusions of a nonmicelle-forming bile acid (taurodehydrocholate) for taurocholate failed to demonstrate any difference in choleretic response or biliary clearance of [(3)H]inulin with the order of bile acid infusion. These experiments demonstrate that a micelleforming bile acid, taurocholate, can increase the permeability of the biliary system to large molecular weight solutes and simultaneously modify the y-intercept and the volume of bile secreted in response to the transported bile acid. Taurocholate may, therefore, modify its own choleretic response, perhaps by altering the structure or function of bile secretory membranes, and appears to be a major determinant of so-called bile acid-independent flow in rhesus monkeys.

Animals↗

Reduction in portal vein blood flow by somatostatin.

Intravenous somatostatin boluses produced striking diminution in portal vein blood flow in dogs (maximally 40--55%). This effect was of rapid onset, without observable changes in hepatic artery flow, systemic blood pressure, pulse or central venous pressure. The duration of action was short, but could be sustained by continuous intravenous infusion. These observations are consistent with an endocrine role of somatostatin in the regulation of nutrient balance.

Animals↗

Investigative approaches to the problem of pancreatic cancer.

A prospective study of 134 patients suspected of having pancreatic cancer is reported. Ultrasonography and duodenal drainage studies are the best initial investigations. Endoscopic retrograde cholangiopancreatography with cytological examination is the test most likely to provide a definitive diagnosis. Arteriography is essential before laparotomy to delineate anomalies in the foregut vasculature. Pancreatic oncofetal antigen is the only tumour marker that is useful in diagnosis and in monitoring therapy.

Adult↗

Non-operative differentiation between pancreatic cancer and chronic pancreatitis.

Eighty-five of 186 patients investigated for suspected pancreatic cancer had an unequivocal final diagnosis of either pancreatic cancer (58 patients) or chronic pancreatitis (27 patients). They had been studied prospectively using ultrasonography, computerized tomography, radionuclide scanning, endoscopic retrograde cholangiopancreatography (ERCP), selective celiac and superior mesenteric angiography, duodenal drainage studies, cytologic studies, serum carcinoembryonic antigen assay, and pancreatic oncofetal antigen assay, The results were compared to determine which test would most frequently and reliably differentiate between pancreatic cancer and pancreatitis in a patient believed to have one or other disease. Criteria for interpreting results, first for highest rate of correct diagnoses, and second for highest accuracy were derived. Applying these criteria, ultrasonography achieved the highest rate of correct diagnoses (97% of patients diagnosed with 84% accuracy). ERCP, duodenal drainage studies, and cytology were the most accurate tests ((86% accuracy each test) but, with this accuracy, ERCP most frequently gave a diagnosis (diagnosis rate: ERCP--70%, duodenal drainage--32%, cytology--35%). The results suggest that ultrasonography is the best noninvasive test, and that a combination of ERCP, pancreatic juice assay and cytology in a single procedure may prove to be the best discriminating investigation.

Adult↗

Surgical treatment of pancreatic cancer.

The problems encountered in the surgical treatment of pancreatic cancer are outlined on the basis of a review of the literature published in the last 15 years and the authors' experience with 157 patients over the period 1970 to 1977. The overwhelming evidence favors resection as opposed to any palliative procedure. Although the number of patients eligible for 5-year follow-up is small, the data suggest that total pancreatectomy with regional lymphadenectomy may be the most appropriate operation.

Biopsy, Needle↗

Studies on an oncofetal antigen, POA.

This paper describes the purification and partial characteristics of a putative oncofetal antigen, POA, which appears to be associated with the pancreas. POA is a glycoprotein of molecular weight between 800,000 and 900,000 daltons. It is found in fetal pancreas and pancreas cancer tissue, but not in normal adult pancreas. It is clearly different from carcinoembryonic antigen, other known tumor associated antigens, acute phase reactants and normal serum proteins. A quantitative rocket immunoelectrophoresis assay was developed for POA. Its specificity was monitored routinely by double immunodiffusion against known fetal and adult standards. The assay was performed on sera from over 700 patients. The results demonstrate that POA is found in the sera of most individuals. However, by far the highest absolute levels and the highest frequency of elevated levels was found in sera of patients with carcinoma of the pancreas. Elevated levels of POA were also found in the serum of a proportion of patients with carcinomas of the lung, stomach, colon, biliary tract, and breast and in a few other individuals with benign conditions. The spectrum of patients who have elevated levels of POA in their serum is quite different from that found with CEA or other known tumor markers.

Antigens, Neoplasm↗

A prospective study of glucose tolerance, insulin, C-peptide, and glucagon responses in patients with pancreatic carcinoma.

Ninety-nine patients suspected of having pancreatic carcinoma were studied prospectively for carbohydrate tolerance. Thirty-two patients were proven subsequently to have pancreatic carcinoma; the remainder served as a control group. There was an increased incidence of carbohydrate intolerance in patients with pancreatic carcinoma compared to the control group. Insulin and C-peptide measurements during glucose tolerance tests suggest abnormal beta cell function and possibly insulin resistance as causes for this abnormality. Although factors related to malignancy in general could partly account for the results, a specific factor occurring in patients with pancreatic carcinoma must also be considered as it could serve as a marker for the early detection of this disease.

Body Weight↗

Prospective evaluation of gray scale ultrasonography in the diagnosis of pancreas cancer.

One hundred thirty-four patients suspected of having pancreas cancer successfully underwent gray scale ultrasound examination of the pancreas. The prospective ultrasound findings were correlated with the final diagnoses, laparotomy findings, and pathology findings. Fifty-four patients had pancreas cancer, confirmed by resection or biopsy in all cases. On ultrasonography, the pancreas was correctly reported to have abnormalities in sixty-one of seventy-eight patients (78 per cent) and correctly reported to have no abnornalities in thirty-eight of fifty-six patients (68 per cent). A correct ultrasound diagnosis of pancreas cancer was made for forty-four of fifty-six patients (81 per cent), and there were thirteen false-positive reports. Ninety-four percent of cancers confined to the head of the pancreas and 70 per cent of cancers at other locations within the gland were detected by ultrasound examination. The correct ultrasound diagnosis was given for fifteen of seventeen patients with resectable pancreas cancer, the degree of associated pancreatitis ranging from minimal to severe. Analysis of the predictive values of positive and negative ultrasound examinations suggests that this test could be used to screen a population of patients with symptoms mildly suggestive of pancreas cancer. The importance of preselecting the level of confidence of a positive test result, a,ove which further investigation is indicated, is emphasized.

Diagnosis, Differential↗

Prospective evaluation of endoscopic retrograde cholangiopancreatography in the diagnosis of periampullary cancers.

In a prospective study of 112 patients suspected of periampullary cancer endoscopic retrograde cholangiopancreatography (ERCP) was successfully performed in 87 patients (78%). Technical failures were due to gastric outlet obstruction in four patients and inability to cannulate the ampulla of Vater in 21 patients. Successfully performed ERCP had both a high sensitivity (92%) and specificity (90%) for periampullary cancer. The few errors in pancreatogram interpretation were due to juxta-ductal cancers and difficulty in differentiating duct changes of cancer from those of chronic pancreatitis. Pancreatic cytology, performed in 21 patients, was reliable, diagnosed two pancreatic cancers when the pancreatogram failed and, if used routinely, assists interpretation of the pancreatogram. Retrograde cholangiography provided a correct diagnosis in six jaundiced patients with normal pancreatograms. Three complications of ERCP occurred in this series.

Ampulla of Vater↗

The prognosis of carcinoma of the colon and rectum complicating ulcerative colitis.

Thirty-three carcinomas of the colon and rectum occurring in patients with ulcerative colitis have been compared with matched controls from a population without colitis. There is no difference in length of survival between the patients in the two groups. More extensive tumor spread in the control group is due to the method of selection.

Adenocarcinoma↗

The prospective evaluation of tumour-associated antigens for the early diagnosis of pancreatic cancer.

An unselected series of 136 patients suspected of having a major intra-abdominal pathological condition had blood drawn and stored as serum. A definitive histological diagnosis was made in all cases, usually by laparotomy. The serum was analysed with coded samples for carcino-embryonic antigen, alpha-fetoprotein and pancreatic oncofetal antigen and all recorded levels above the upper limit of normal for that test were taken as a positive result. Results were analysed to give the predictive value of a positive test and a negative test for each antigen. A negative pancreatic oncofetal antigen test was found to be useful in excluding a diagnosis of pancreatic cancer.

Antigens, Neoplasm↗

The effect of small bowel resection and subsequent precise antrectomy on lower esophageal function in rhesus monkeys.

The lower esophageal high pressure zone (HPZ) was characterized manometrically and reflux status determined in eight male rhesus monkeys. The studies were repeated six weeks and six months after 50 per cent distal small bowel resection. At the same time fasting serum gastrin and gastric inhibitory polypeptide values were assayed. In seven animals precise antrectomy with gastroduodenal anastomosis was performed and the studies repeated. HPZ pressure increased from 6.7 +/-0.67 mm Hg (+/-1 SEM) to 10.3 +/- 0.76 mm Hg at six weeks (p less than 0.005). At six months the pressure was 9.3 +/- 1.02 mm Hg (p less than 0.02) and after antrectomy 15.2 +/- 3.1 (not significant from 6 month value, p less than 0.02 from control). Serum gastrin and GIP values showed significant elevations at six weeks, but six month and postantrectomy results were not statistically different from control. Reflux episodes for the group were reduced at six weeks and six months. After antrectomy increased reflux was noted.

Animals↗