Recurrent massive hemorrhage in patients with achlorhydria and atrophic gastritis.
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Biomedical subjects
Publications and source records attributed to N Zamcheck.
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The transport of human alpha 1-acid glycoprotein from the circulation to the bile has been studied in the rat. Biliary excretion was proportional to the i.v. injected dose, and the percentage excreted remained constant. The amount excreted in the bile (over 4 hr) was inversely related to the rate of hepatic (hepatocyte) uptake and the galactose receptor which is specific for asialo glycoproteins was not involved. Reinjection of the glycoprotein excreted in bile resulted in a similar proportion of the dose being reexcreted, suggesting that a subset of the glycoprotein is not selected for excretion in bile. Transit times from blood to bile for glucagon, insulin, alpha 1-acid glycoprotein, fetuin, albumin, and carcinoembryonic antigen were directly related to their molecular weights. Removal of sialic acid from the asialo glycoproteins did not affect these transit times. Possible mechanisms for the biliary excretion of alpha 1-acid glycoprotein are discussed.
The biliary output of carcinoembryonic antigen (CEA) in bile fistula rats following treatment with the microtubule poisons vinblastine and colchicine increased 3-fold over a 4-hr period. Cytochalasin B and the inactive colchicine derivative lumicolchicine had no effect. These treatments did not effect the rate of CEA clearance from the circulation. Biliary output of low molecular weight fragments from CEA degradation was decreased in the presence of colchicine and vinblastine. Mechanical obstruction of the bile duct for 3 days followed by relief of obstruction resulted in a 3-fold increased output of CEA into the bile. These results are consistent with a paracellular mechanism for CEA transport from blood to bile. Biliary duct obstruction and vinblastine and colchicine probably affect the permeability of junctional complexes between hepatocytes allowing CEA to penetrate more easily.
The median survival of all patients with hepatic metastases from colorectal cancer referred to the Sidney Farber Cancer Institute during a five-year period was 12.5 months. Two major factors influenced survival. The first was extent of disease at presentation. The second was the histologic grade of the cancer. The median survival of patients presenting with the least disease, characterized by less than four liver nodules visible on liver scan (n = 38), normal liver size on physical examination (n = 60), normal liver function test results (n = 30), and normal performance status (n = 91), was between 18 and 24 months, regardless of treatment. The median survival of those few patients (n = 13) who had objective responses to a variety of treatments, most of whom also had minimal disease at presentation, was also 24 months. Patients whose tumors were poorly differentiated or who had abnormal performance status or weight loss of greater than 10 per cent at presentation survived only six months (median). Those with four or more liver nodules, hepatomegaly (greater than 16-cm vertical span on physical examination), or abnormal liver function test results, survived ten, eight, and 12 months (median), respectively. It is concluded that a significant group of patients survived longer than would have been predicted by earlier literature surveys after the diagnosis of colorectal cancer metastatic to the liver. It is suggested that future therapeutic trials, using survival as a measure of response of patients with liver metastases from colorectal cancer, must be prospectively controlled before selection factors can be differentiated from significant therapy effect.
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The Gastrointestinal Tumor Study Group conducted a carcinoembryonic antigen standardization experiment to address the issue of reproducibility of assays performed at participating institutions and a central laboratory. Samples were drawn in quadruplicate from 37 patients, representing five participating institutions. Systematic biases were observed in four of the five institutions: two series were consistently higher and another two series were consistently lower than the corresponding central laboratory determinations. Significantly higher variations were found in three of the five series, comparing the sample variances associated with the matching assay series. Overall, the standard deviation associated with the central laboratory was one third that of the participating institutions. These results point toward the limitation of pooling multi-institutional carcinoembryonic antigen data. The use of multivariate models with parameters for institution comparison is proposed as a solution to this problem.
Carcinoembryonic antigen (CEA), the zinc glycinate marker (ZGM) and epithelial membrane antigen (EMA) have been described as epithelial or tumour markers of varying specificity. These antigens were studied by immunoperoxidase localization in selected cell blocks of 62 pleural or peritoneal effusions and compared to cytological findings and review of the clinical records. By cytological criteria, 25 of the cell blocks were positive for malignancy, 30 negative, and 7 inconclusive. CEA, ZGM, and EMA by immunoperoxidase staining were localized on the cell surface and often in the cytoplasm of malignant cells, in 11/25 (44 per cent), 17/25 (68 per cent) and 22/25 (88 per cent) of the positive cell blocks respectively. Ten (40 per cent) of these cases were positive for all three antigens, 7 (28 per cent) for two, and 6 (24 per cent) for one. Of the 7 cases which were inconclusive on routine cytological reporting, 5 were positive for at least one marker. In 3 of the 5 a diagnosis of malignancy was confirmed, and in the other two was strongly suspected as malignant on clinical grounds. Macrophages were sometimes positive for one or more markers (but showed cytoplasmic staining only) and mesothelial cells in some cases stained positively for EMA but were always negative for CEA and ZGM. Localization of the 3 antigens in cells of malignant effusions was compared with their localization in the primary tumours in 9 cases. Localization corresponded for CEA in 7 of 9 cases, for EMA in 8 of 8 an for ZGM in only 2 of 9. Effusion fluid levels for CEA were compared with the cytological and immunocytochemical findings in 30 cases. Mucin stains performed on the cell blocks were also compared with the immunoperoxidase findings.