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Biomedical subjects

V L Go

Publications and source records attributed to V L Go.

At least 271 records · Page 15Linked to original sources

Tumor-associated antigen levels (carcinoembryonic antigen, human chorionic gonadotropin, and alpha-fetoprotein) antedating the diagnosis of cancer in the Framingham study.

Determinations of carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) were done by use of frozen serum samples antedating the diagnosis of cancer for 9 pancreatic and 8 gastric carcinoma patients from the Framingham Heart Study. The longest intervals for elevated antigens before cancer diagnosis were 10 months for CEA and 26 months for HCG. (The single elevated AFP was found in a sample 10 days before clinical diagnosis.) Samples from 31 controls matched with the cancer subjects by age, sex, vital capacity, and smoking status showed over 20% "false" positive CEA elevations (all smokers with low vital capacities) and over 20% borderline false positive HCG elevations in postmenopausal females. Although 10-26 months' lead time could infer some potential for use of these tumor-associated antigens to help detect malignant neoplasms at an earlier stage, a serious problem of frequent false positives prevents CEA and HCG levels from being useful as cancer-screening tests at this time.

Adult↗

Postprandial gastric, pancreatic, and biliary response to histamine H2-receptor antagonists active duodenal ulcer.

Histamine H2-receptor antagonists are potentially useful agents in duodenal ulcer and knowledge of their effect on postprandial digestive events will contribute to their clinical application. We studied the effect of 200- and 300-mg doses of cimetidine, an H2-receptor antagonist, taken with an ordinary meal, on gastric, pancreatic, and biliary function. Both doses significantly reduced acid output and its delivery into the duodenum. Gastric secretory volume and pepsin output were less affected. Acid inhibition was related to blood drug levels and was less than that previously found at night in nocturnal fasting studies. As the stomach emptied the food, the gastric pH rose. The fractional gastric emptying rate, pancreatic enzyme, and bile acid outputs were unaltered. Cimetidine taken orally with meals at these doses is a potent gastric antisecretory agent without affecting other postprandial gastric, pancreatic, or biliary functions.

Adult↗

Cytotoxicity of ricinoleic acid (castor oil) and other intestinal secretagogues on isolated intestinal epithelial cells.

Epithelial cells were isolated from hamster small intestine by a technique of vibration and used to measure cytotoxicity in vitro of certain substances known to stimulate intestinal fluid secretion. These secretagogues have laxative properties and produce mucosal damage in vivo. Compounds tested were ricinoleic acid (caster oil), dioctyl sodium sulfosuccinate, oleic acid, sodium deoxycholate and sodium cholate. Cytotoxicity was assessed by: 1) exclusion of trypan blue; 2) release of intracellular (prelabeled) 51Cr; and 3) inhibition of cellular uptake of 3-O-methylglucose. Ricinoleate produced a dose-dependent (0.1-2.0 mM) cytotoxicity as assessed by all three methods. Oleic acid, a nonhydroxylated analog of ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate, was less potent. The dihydroxy bile acid, deoxycholate, was equipotent with ricinoleate but its trihydroxy congener, cholate, was less potent. Dioctyl sodium sulfosuccinate had cytotoxicity similar in magnitude to that of ricinoleate and deoxycholate. Cytotoxicity of these agents to isolated cells may relate to their secretory potential in vivo, their abilities to produce structural change at the mucosal surface and their laxative properties.

Animals↗

Gastric secretion and emptying after ordinary meals in duodenal ulcer.

We have studied the gastric response to an ordinary solid-liquid meal in 12 patients with active duodenal ulcer and 8 healthy volunteers. Our method employs gastric and duodenal markers to quantify acid, pepsin, and volume outputs in response to the meal, without manipulating intragastric pH. Intragastric volume, rate of gastric emptying, delivery of acid into the duodenum, and serum gastrin response were also measured simultaneously. On a separate day, peak acid output in response to betazole (1.5 mg per kg subcutaneously) was determined. Our results indicate an inappropriately prolonged gastric secretory response to meals in duodenal ulcer disease, without a concomitant increase in peak postprandial secretory rates or an increase in serum immunoreactive gastrin levels. Further, the stomach in duodenal ulcer disease did not "retain" the additional acid secreted in the later postprandial period, and abnormally high rates of acid delivery into the duodenum occurred. Our data are consistent with a dual defect in the duodenal mechanisms regulating both acid secretion and acid delivery into the duodenum.

Adult↗

Meconium ileus equivalent complicating cystic fibrosis in postneonatal children and young adults. Report of 12 cases.

Twelve patients with meconium ileus equivalent complicating cystic fibrosis in the postneonatal period were seen at the Mayo Clinic in the years 1950 through 1975. In a child or young adult with known or suspected cystic fibrosis, the triad of recurrent colicky abdominal pain, a mass in the right lower quadrant, and mechanical intestinal obstruction provides a clue to diagnosis of meconium ileus equivalent. The clinical suspicion of meconium ileus equivalent may be confirmed by meglumine diatrizoate (Gastrografin) enema, which in most uncomplicated cases also serves as treatment.

Adolescent↗

Prednisone for chronic active liver disease: pharmacokinetics, including conversion to prednisolone.

To determine the effect of impaired liver function on conversion of prednisone to prednisolone, and to investigate the relationship of this to responses to treatment with prednisone, we measured serum prednisone and prednisolone by radioimmunoassay after 10 mg of prednisone was given by vein to 10 healthy volunteers, 6 untreated patients with severe chronic active liver disease (CALD), 10 patients with prednisone-induced remission of CALD, and 3 patients with CALD deteriorating despite treatment with prednisone. Prednisone disappearance was comparable in all groups and substantial values for serum prednisolone appeared in all groups within 0.3 hr. Minor differences between the groups included lower than normal serum prednisolone in severe CALD and treatment failure; a higher percentage of nonprotein bound prednisolone in such patients; and an association between earlier treatment with prednisone and an increased disappearance rate of prednisolone. We conclude that no major defect of prednisone metabolism occurs in CALD and that failure of this condition to respond to therapy with prednisone is caused by other factors.

Adult↗

Effect of proximal gastric vagotomy on gastric acid hypersecretion and hypergastrinemia after massive small bowel resection in dogs.

Fasting and postprandial gastric acid secretion and gastrin were determined in Heidenhain pouch dogs before (C) and after (R) massive enterectomy (five dogs) and after additional proximal gastric vagotomy (PGV) in three dogs. Basal acid output was unchanged (C = 7 +/- 2 microneq/hour; R = 11 +/- 4 microneq/hour), but postprandially the hourly (third through eighth hour) and cumulative acid outputs (C = 3.6 +/- 0.3 mEq/8 hour; R = 7.2 +/- 0.4 MEq/8 hour) were significantly increased by resection (P less than 0.001). Similarly, fasting gastrin was unaltered by resection (C = 41 +/- 2 pg/ml; R = 46 +/- 8 pg/ml), whereas hourly gastrin concentrations significantly (P less than 0.05) exceeded control values. Increased gastrin correlated linearly (P less than 0.02) with increased acid output. After PGV, basal acid levels remained unchanged (R = 4 +/- 2 micronEq/hour; PGV = 9 +/- 4 micronEq/hour), but postprandial acid output significantly exceeded prevagotomy values at all time periods (P less than 0.05). Cumulative acid output also was increased (R = 6.8 +/- 0.6 MEq/8 hour; PGV = 11.2 +/- 0.6 mEq/8 hour; P less than 0.001). Serum gastrin, however, remained unchanged. Hypersecretion of acid from Heidenhain pouches after massive enterectomy is increased further by PGV without a concomitant increase in serum gastrin.

Animals↗

Isolation and immunochemical and chemical characterization of carcinoembryonic antigen-like substances in colon lavages of healthy individuals.

Material with carcinoembryonic antigen (CEA)-like activity, isolated from colon lavages of healthy individuals, has been chemically characterized. The CEA-like activity in these lavages was purified by gel filtration on Sepharose 6B and Sephadex G-200 and by affinity chromatography on concanavalin A linked to Sepharose. The purified material migrated in polyacrylamide-sodium dodecyl sulfate electrophoresis as a single diffuse band with mobility identical with that of tumor CEA. The material with CEA activity from tumor tissue and from normal colon lavages gave lines of identity in double diffusion experiments and had similar inhibition curves with esssentially the same specific activities in a radioimmune assay for tumor CEA. The amino acid and carbohydrate compositions were similar to that observed for CEA tumor preparations. Lysine was the single amino terminus. Methylation analysis demonstrated that the monosaccharide linkages were similar to those in CEA isolated from tumor tissue.

Adult↗

Participation of the jejunum and ileum in postprandial gastric secretion in man.

The role of the small intestine in postprandial gastric secretory function was determined in 6 normal volunteers by diverting chyme at the ligament of Treitz and comparing the results with those obtained in the same individuals when chyme was exposed to the entire small intestine. Because diversion of chyme caused a lesser gastric secretory response, it is concluded that the small intestine contributes appreciably to the magnitude of gastric secretory responses to meals.

Adult↗

Prospective evaluation of the pancreatic secretion of immunoreactive carcinoembryonic antigen, enzyme, and bicarbonate in patients suspected of having pancreatic cancer.

We undertook to test the recent suggestion that measurement of immunoreactive carcinoembryonic antigen (CEA) in pancreatic secretion may be useful in diagnosis of pancreatic cancer. Using duodenal intubation and a perfusion method in 57 cases, we measured the rate of pancreatic CEA secretion into the duodenum under basal saline perfusion, alone and with continuous intravenous infusion of secretin (2 clinical units per kg per hr) and of cholecystokinin-pancreozymin (CCK, 15 Crick-Harper-Raper units per kg per hr); and we compared the CEA output with secretion of trypsin, lipase, and bicarbonate under the same conditions. Subsequent laparotomy revealed pancreatic carcinoma in 25 patients, pancreatitis in 7, other intraabdominal malignancies in 6, and benign nonpancreatic disorders in 19. CEA output rates did not differentiate all pancreatic-cancer patients from other patients in any test condition. However, pancreatic enzyme outputs were abnormal with almost 90% of cancers of the pancreatic head and with 75% of cancers of the pancreatic body and tail. For detection of pancreatic cancer, enzyme and bicarbonate outputs in response to CCK are more accurate than pancreatic CEA or bicarbonate outputs in response to secretin. Since CCK-stimulated enzyme outputs can be related accurately to malabsorption (not reported here), we prefer them to bicarbonate output for assessment of pancreatic function.

Adult↗

Relationships between fasting and postprandial pancreaticoduodenal pressures, pancreatic secretion, and duodenal volume flow in the dog.

We have developed a canine model which allows simultaneous quantification of pancreatic enzyme outputs, duodenal volume flow, and pancreatic and duodenal pressures under physiological circumstances. Twelve studies on 4 conscious healthy dogs demonstrated that mean fasting pancreatic pressure was 5 to 10 cm H2O higher than mean fasting duodenal pressure. Furthermore, 8 min after ingestion of a meal, both the pancreatic and the duodenal pressure increased. Surprisingly, the mean duodenal pressure was higher than the mean pancreatic pressure 20 min after feeding. This relationship lasted for 30 min. Lastly, elevation of postprandial pancreatic pressure occurred concomitantly with increased pancreatic enzyme output, and duodenal pressure increased with increased duodenal volume flow. The observed large postprandial duodenal volume flows associated with duodenal pressures greater than pancreatic duct pressures may favor reflux of duodenal contents into the pancreatic duct. These relationships may be important in the pathogenesis of postprandial pancreatitis and in the induction of pancreatic cancer.

Animals↗

Alimentary-tract ganglioneuromatosis. A major component of the syndrome of multiple endocrine neoplasia, type 2b.

Although the syndrome of multiple endocrine neoplasia, type 2b, is known to comprise mucosal ganglioneuromatosis, medullary thyroid carcinoma, pheochromocytoma and skeletal anomalies, we wish to document the importance of the alimentary-tract components. In nine patients with this syndrome, we found diffuse ganglioneurmatosis extending from the lips to the rectum. Alimentary symptoms, constipation or diarrhea or both were present in six of these patients. Similar symptoms were present in six of seven other affected patients from whom alimentary-tract tissue was not obtained. Five of the 16 patients had megacolon, which led to operation in four, and a sixth patient had colectomy for diverticulitis complicating diffuse diverticulosis. The alimentary manifestations warrant greater emphasis, not only because they were prominent in the patients whom we studied but also because in 14, these manifestations were present before the endocrine neoplasms were detected.

Adolescent↗

Cimetidine suppression of nocturnal gastric secretion in active duodenal ulcer.

Nocturnal pain and gastric hypersecretion are common in duodenal ulcer. Therefore, we investigated the antisecretory effects of a new H2-receptor antagonist, cimetidine, in 200-, 300- or 400-mg doses, taken orally at bedtime. The 200-mg dose did not cause a statistically significant change in nocturnal (midnight to 7 a.m.) acid output and had only a borderline effect on pH. However, the 300-mg and 400-mg doses significantly (P less than 0.001) lowered acid output and increased (P less than 0.01) intragastric pH. All doses caused substantial decreases in secretory volume output. After a 400-mg dose, half the patients remained anacidic for eight hours. Dose-related increases of drug blood levels were observed and correlated with the degree and duration of inhibition of acid output. Serum gastrin levels were unaffected. Cimetidine appears to be a potent inhibitor of nocturnal gastric secretion.

Administration, Oral↗

Carcinoembryonic antigen: clinical application.

Carcinoembryionic antigen (CEA) a glycoprotein extracted from colonic cancer tissue (beta-globulin electrophoretic mobility, sedimentation coefficient 7 to 8S, and mol wt approximately 200,000) can be detected and measured by radioimmunoassay. Clinical evaluations of CEA determination have given the following results: In health: (1) Serum CEA level is not influenced by sex, age, blood type, time of blood sampling, or family history of cancer; (2) serum CEA level is influenced by a history of smoking or inflammatory disease of the bowel, lung, pancreas, and other organs (occasionally, a CEA level as high as 10 ng/ml is noted); and (3) currently, CEA positivity is defined as greater than 2.5 ng/ml, however, 5 ng/ml may be more realistic. In cancer: (1) CEA level may be increased in primary cancer of the gastrointestinal (GI) tract as well as in non-GI neoplasia; (2) the CEA test is not recommended for screening to detect early cancer; (3) serum CEA level depends on the stage of the neoplasia and usually is not influenced by the grade of differentiation; and (4) markedly increased (greater than 25 ng/ml serum CEA values are highly suggestive of metastatic cancer, particularly hepatic metastasis. In biological fluid: The CEA or CEA-like activity can be measured in gastrointestinal secretions. Quantitative studies of CEA levels in such fluids may yield more information than is obtainable from studies of serum. However, this possibility needs more study at present. Therefore, the currently available CEA tests cannot replace any of the now standard diagnostic methods for cancer detection. This use for assessment of therapy in selected patients or for following those known to be a high risk for cancer appears promising in preliminary studies, but clinical value, if any, remains to be determined.

Body Fluids↗

Hemoccult detection of fecal occult blood quantitated by radioassay.

Results from the quaiac slide or Hemoccult (HO) test for fecal occult blood were compared with quantitative determinations of gastrointestinal loss after intravenous administration of 51Cr-labeled red cells. Subjects were 80 consecutive patients, without dietary restriction, who were referred because of clinical suspicion of gastrointestinal blood loss or complex anemia. A total of 555 stool specimens analyzed for 51Cr loss were graded negative, trace, or positive by the HO method. Of 338 specimens containing 0-2 ml/day by isotope assay, 7.4% were positive to the HO qualitative test. Loss of at least 10 ml/day in 51Cr equivalent was necessary to assure that the majority of HO reactions would be positive. Of specimens containing more than 30 ml/day, 93% were positive. The ratio of 51Cr-labeled red cell equivalents to stool volume and the percentage of positive HO reactions increased together. When this ratio exceeded 10%, two thirds of the HO responses were positive.

Adolescent↗