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Biomedical subjects

J C Thompson

Publications and source records attributed to J C Thompson.

At least 487 records · Page 27Linked to original sources

Cholecystokinin metabolism in man and dogs.

We have developed a sensitive, specific and reproducible radioimmunoassay for cholecystokinin (CCK) with which basal levels of CCK of between 400-800 pg/ml have been measured in normal man, in patients with diabetes and with duodenal ulcer disease, and in normal dogs. After a meal, circulating levels of CCK rose to 1000-1200 pg/ml in human subjects. Release of CCK was more rapid in diabetic and duodenal ulcer patients than in normal subjects, but elevated postprandial levels persisted much longer in normal subjects. Patients with the Zollinger-Ellison syndrome had elevated values of cholecystokinin which rose after a meal. Lack of correlation between elevated basal levels of gastrin and CCK in patients with the Zollinger-Ellison syndrome suggest that the hypercholecystokininemia may be absolute. The disappearance half-time of exogenous CCK was about 21/2 minutes in normal subjects as well as in diabetic and duodenal ulcer patients. Studies in dogs demonstrated no uptake of basal levels of cholecystokinin by the kidney; on infusion of exogenous CCK-33, the kidney extracted 43% of the total CCK presented and 56% of the integrated CCK. We conclude that: 1) circulating basal and postprandial levels of CCK may be measured in a reproducible fashion; 2) postprandial release of CCK is more rapid in diabetic and duodenal ulcer patients than in normal man; 3) the disappearance half-time of exogenous CCK in man and dogs is about 21/2 minutes; 4) the kidney is a major site for uptake of CCK.

Animals↗

Natural history and experience with diagnosis and treatment of the Zollinger-Ellison syndrome.

With better methods of diagnosis, patients will be identified earlier in the course of their disease and will often have atypical and borderline manifestations of the syndrome. Serum gastrin measurements with calcium and especially with secretin challenge will be the most important method of diagnosis. Any patient with acid hypersecretion who has a high serum gastrin level that does higher on secretin infusion should be considered to have the Zollinger-Ellison syndrome. A firm diagnosis of the Zollinger-Ellison syndrome should be made, if at all possible, prior to operation. At operation, a thorough search of the pancreas, duodenum, stomach, greater and lesser omentum and liver should be made for primary and secondary gastrinomas. If the preoperative data firmly establish the diagnosis of the Zollinger-Ellison syndrome, a total gastrectomy should be carried out even if no primary tumor is found. Similarly, a total gastrectomy should be done even if there are massive hepatic metastases. If total gastrectomy is not performed, the patient is apt to die of complications of acid hypersecretion. The only possible exceptions to the rule of always performing a total gastrectomy are in asymptomatic patients with easily excisable tumors or patients with tumors of the duodenum that are easily excisable, providing that in both instances after the excision of the tumor the output of gastric acid as measured at operation is immediately halted. All possible metastatic tumor tissue should be removed. The more tumor tissue removed, the longer the patient will survive. Metastases should be treated aggressively. They do not disappear after total gastrectomy in our experience, and they may kill patients. Patients should be followed after operation with serial measurements of serum gastrin concentrations and by hepatic scintillation scans and hepatic angiography. If hepatic metastases develop, intrahepatic artery infusions of 5-fluorouracil may slow tumor growth.

Adenocarcinoma↗

Interlaboratory reproducibility of gastrin measurements by radioimmunoassay.

A collaborative study was conducted to determine interlaboratory variations in the measurement of gastrin by radioimmunoassay (RIA). A kit containing reagents for a communal RIA method, as well as test samples containing different amounts of human synthetic gastrin (SHG I) and test samples of serum from a fasting normal patient admixed with varying volumes of serum from a patient with the Zollinger-Ellison syndrome, was sent to each collaborating investigator. Each investigator was requested to measure the gastrin concentrations in test samples by means of the communal RIA method, as well as the RIA method utilized in his or her laboratory. Use of the communal RIA method resulted in no significant interlaboratory variation in the determination of gastrin concentration in SHG I test samples and a maximum two- to threefold variation in determination of gastrin serum test samples. In contrast, when individual RIA methods were used to measure gastrin concentrations, the amount of SHG I in test samples reported by one laboratory was significantly different than that reported by the other three. In addition, use of different RIA methods resulted in a 2- to 19-fold interlaboratory variation in serum gastrin measurements and the maximum variation was found when the gastrin in normal fasting serum was measured. Increased variations in results, when different RIA methods were used, may be due to differences in preparation and purification of labeled antigen, to differences in separation of bound from free hormone, and to differences in the antibodies themselves.

Gastrins↗

Gastrin release by ethanol in man and in dogs.

In man, oral or intravenous administration of ethanol caused a small but definite increase in peripheral serum gastrin concentration (measured by radioimmunoassay). In dogs, perfusion of the antrum with 10% ethanol caused an immediate increase in gastrin levels in the antral venous outflow. Acidification of the perfusate did not totally block the gastrin release from the antrum. Intravenous infusion of ethanol in dogs caused release of gastrin from the antrum.

Administration, Oral↗

Extraction of circulating endogenous gastrin by the gastric fundus.

The effect of circulatory transit of the gastric fundus on serum levels of endogenous gastrin measured directly by radioimmunoassay has been studied in 14 dogs. Gastrin was measured in samples obtained simultaneously from the arterial inflow and venous outflow of the gastric fundus. During basal conditions, transit of the gastric fundus resulted in no change in gastrin concentration. During periods of stimulated gastrin release from the antrum, nine of the 14 dogs demonstrated a significant gastric acid secretory response. In these dogs there was a significant arteriovenous difference (approximately 30%) in circulating gastrin values. In the remaining five dogs, which did not demonstrate a significant gastric acid secretory response, there was no arteriovenous difference in circulating gastrin values. It is concluded that the gastric fundus is an important site for the inactivation of stimulated levels of circulating gastrin.

Acetylcholine↗