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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 56 (2000), S. 335-342 
    ISSN: 1432-1041
    Schlagwort(e): Key words Hypoglycemia ; ATP-sensitive K+ channel ; Cibenzoline
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Objective: A case-control study was carried out to compare the risks of hypoglycemia caused by disopyramide and cibenzoline. Methods: We selected 91 subjects with hypoglycemia from among 14,156 outpatients who consulted the National Cardiovascular Center (NCVC) and received drug therapy between September 1997 and February 1998. We used the fasting blood sugar (FBS) level of 75 mg/dl or less as the cut-off level to screen for hypoglycemia. For each case, five controls matched for gender and age were selected from the clinical division consulted by relevant subjects. Results: Ninety-one cases and 455 controls were enrolled in this study. Of 91 cases with hypoglycemia, 8 (8.8%) were treated with cibenzoline and 3 (3.3%) with disopyramide. The percentage of cases treated with cibenzoline was greater than that in the controls (1.5%), and the prescription frequency of cibenzoline during the study period was 2%. With adjustment for potential confounding factors using conditional logistic regression, hypoglycemia was significantly correlated with the use of cibenzoline [OR 8.0 (95% CI 1.7–36.8)], insulin [OR 48.4 (95% CI 8.8–267.2)], and thyroid agents [OR 13.0 (95% CI 1.1–160.4)]. An increased risk of hypoglycemia associated with the use of sulfonylureas was not detected. In additional logistic regression analysis, including the variables with individual sulfonylureas, glibenclamide but not gliclazide significantly increased the risk of hypoglycemia. The use of disopyramide did not affect the risk of hypoglycemia. In separate analyses for diabetic and non-diabetic patients, the risks of hypoglycemia associated with the use of drugs other than β-blocking agents in non-diabetic patients were estimated to be lower than those in diabetic patients. Conclusion: The use of cibenzoline was significantly correlated with an increased risk of hypoglycemia.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-1335
    Schlagwort(e): Stomach ; Signet ring cell carcinoma ; Cell turnover ; Tritiated thymidine autoradiography
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Signet ring cell carcinoma was induced in canine stomachs by N-ethyl-N′-nitro-N-nitrosoguanidine, and modes of cell proliferation and turnover in the carcinoma were studied by 3H-thymidine autoradiography in conjunction with morphometric analysis. From 2 to 15 months after the cessation of 8 months carcinogen treatment, carcinomas in an early stage were obtained. Most of the cancer tissues confined to the lamina propria showed a layered structure. This comprised three layers; the superficial and the deep layer were composed of signet ring cells, and the middle layer was composed of small round cells. The dogs were labeled with 3H-thymidine by s.c. injection and by local infusion of the celiac artery. Flash-labeled autoradiographs revealed that most 3H-thymidine incorporating cancer cells were located around the middle layer, with a small amount of mucin. Using a pulse labeling experiment, those labeled carcinoma cells were shown to migrate from the middle layer towards the surface. Morphometric analysis of the autoradiographs showed that the small cells in the middle layer migrated upwards and produced mucin to become full-blown signet ring cells by 5.5 days. In 15 days, most labeled cancer cells in the superficial layer had disappeared. This mode of cellular turnover appeared to mimic a cell renewal system of the normal gastric mucosa. If the cancer cells turn over in this way, the tumor must grow slowly, remaining as an intramucosal cancer for a relatively long period.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-1335
    Schlagwort(e): Stomach ; Signet-ring-cell carcinoma ; Cell kinetics ; Bromodeoxyuridine ; N-ethyl-N′-nitro-N-nitrosoguanidine
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Signet-ring-cell carcinomas were induced in the stomach of 12 beagle dogs by p.o. administration ofN-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), and the morphology and modes of cell proliferation in an incipient stage of cancer growth were studied with bromodeoxyuridine (BrdUrd) incorporation. From 5 to 27 months after the completion of 8 months' carcinogen treatment, minute carcinomas were found in the stomachs of 9 dogs. Before sacrifice, the dogs were given a single or repeated i.v. injections of BrdUrd for 1–3 days. Minute signet-ring-cell carcinomas were found to form a layered structure, in which the cancer cells proliferated in the lamina propria at the gland-neck level and differentiated to postmitotic signet-ring cells at the upper and lower levels of the mucosa. From repeated injections of BrdUrd, the time required for all the proliferative cells to be labelled with BrdUrd (reflecting the maximum cellcycle time) was estimated to be 1.7 days for the normal glands, and 2.7 days for minute signet-ring-cell carcinomas. From the labelling index with BrdUrd as well as from the morphology, earliest carcinomas were identified in the single gland. There remained atrophic normal epithelium commonly in the single-gland lesions. Proliferative atypical cells appeared to be shed into the stroma passively through the atrophy and subsequent collapse of the gland rather than through active invasion. This may be a reason why cancer cells in minute signet-ring cell carcinomas preserved the normal pattern of cell renewal movement to form the layered structure.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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