[Effect of cancer chemotherapy for unresectable cancer of the pancreas].
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Biomedical subjects
Publications and source records attributed to I Miyazaki.
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The isolated islets of Langerhans are the most available donors for transplantation. As the preservation of the isolated islets is difficult, we attempted to keep these tissues viable by use of an organ culture. Islets of Langerhans from adult Wistar rats were isolated by a collagenase technique and cultured in air-CO2 (95-5%) incubator at 37 degrees C. Insulin contents of the culture media which was changed every 3 days ranged from 1097 to 1434 microunits/ml during the 80 days' culture period. Transplantation of these islets into the portal vein of streptozotocin-induced diabetic rats resulted in a good recovery from the diabetic state. These studies indicate that cultured islets do preserve their original biological abilities.
To determine the benefits of surgical treatment for patients with carcinoma of the extrahepatic bile duct, data on 100 patients with this disease who had been surgically treated in our clinic during the past 18 years were evaluated. These patients were grouped into three, i.e., upper, middle and lower bile duct groups. Patients with periampullary tumor were excluded from this study. Surgical procedures consisted of resection of the tumor, including hepatic resection and dissection of the regional lymph nodes, and a bypass operation of the extra- or intrahepatic bile duct. Resectability rates of the tumor were 21.6% in upper, 82.4% in middle, and 50% in lower bile duct groups. Average survival times of patients who had a resection of the tumor were 30.3 months in the upper bile duct group, 35.9 months in middle (the longest, 13 years and 3 months) and 22.5 months in lower bile duct group. Survival rates of overall patients with resection of tumors were 64.5% at one year, 29.0% at 3 years, and 12.9% at 5 years after surgery, respectively. The middle bile duct group showed the most favorable operative results of all the groups, an extended resection of the tumor should be carried out to obtain for a longer survival.
Investigations of the lymphatic routes using dye during operations and histological studies on the resected specimen of the pancreas and autopsied cases with pancreatic carcinoma have led to the conclusion that the surgery should be performed more extensively to improve the results and should consist of a complete lymphatic excision surrounding the celiac axis and the trunk of the superior mesenteric artery including dissection of the nerve plexus and wide retroperitoneal dissection surrounding the pancreas, upwards to the level of adrenal glands, and downwards to the level of iliac bifurcation. A translateral retroperitoneal approach was found to be the most useful and safe method for such extended resection in patients with pancreatic carcinoma. Our radical procedure for pancreatic carcinoma is described herein.
Recently many investigators have attempted transplantation of isolated islets of Langerhans in an expectation of therapeutic effects in patients with diabetes. In the course of time, preservation of the islets was found to be a prerequisite for successful transplantation. In the present studies, we used our newly designed method of preserving islets, i.e., cryopreservation combined with the cultural process before and after freezing, and we examined the insulin-releasing activity of the islets and attempted transplantation of the islets so-obtained. As to the insulin-releasing activity, the islets cryopreserved after short-term culture increased insulin output as compared with those cryopreserved without culture. Damage to Langerhans' islets resulting from isolation and cryopreservation was overcome during the culture. Transplantation of Langerhans' islets cultured for 3-4 days before and after the cryopreserving process produced favorable results.
Vasodilator and hypotensive effects of (+) and (-) nicardipine were investigated in anesthetized dogs. When administered intravenously, (+) nicardipine was 3 times as potent as the (-) isomer in increasing vertebral blood flow and in lowering mean blood pressure. When injected into the vertebral artery, (+) nicardipine was also 3 times as potent as the (-) isomer in increasing vertebral blood flow. Upon both routes of administration, the duration of the action after (+) nicardipine was longer than that after the (-) isomer. However, there were no differences of plasma nicardipine levels after intravenous injection of both isomers to conscious beagle dogs. The LD50 values of (+) nicardipine in mice and rats upon intravenous injection were only 1.5-2 times smaller than those of the (-) isomer. These results indicate that there exists a stereoselectivity of vasodilator and hypotensive actions among the nicardipine isomers.
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Studies on the structure-activity relationship using 9 new 3-sulfamoylphenylethylamines revealed that YM-09538, YM-09649 and YM-09686 were competitive antagonists at both beta- and post-synaptic alpha-receptors. The following order of adrenoceptor blocking activities was obtained : propranolol greater than labetalol greater than YM-09538 greater than YM-09649 greater than YM-09686 for beta-receptors and prazosin greater than YM-09686 greater than YM-09649 greater than YM-09538 greater than phentolamine greater than labetalol for postsynaptic alpha-receptors. In contrast to phentolamine, three YM-compounds showed low affinities for presynaptic alpha-receptors similar to prazosin and labetalol. These antagonists except propranolol effectively lowered blood pressure in conscious SHR and their relative effectiveness parallels the postsynaptic alpha-blocking activity. At hypotensive doses, phentolamine markedly and prazosin, YM-09686 and YM-09649 moderately increased heart rate, whereas YM-09538 and labetalol failed to increase the rate. These results indicate that the postsynaptic alpha-blocking activity of YM-compounds contributes to their hypotensive activities and that both beta-blocking and low presynaptic alpha-blocking activities contribute to attenuation of the tachycardia.
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A 62 year-old man was admitted with the chief complaint of a epigastric pain and difficulty of swallowing. Examination of the upper gastrointestinal tract revealed a calcified mass causing a smooth filling defect at the lesser curvature of the cardia. At laparotomy, a localized tumor was detected beneath the serosa of the stomach. The excised tumor was 4 x 4 x 1.6 cm and the pathological diagnosis was calcified leiomyoma probably due to cytoplasmic degeneration. In this paper, details of the case are described and the related literature is reviewed.
A 33 year-old woman was admitted with chief complaint of abdominal pain and high fever. A barium-enema showed serration and a tumor was seen in the proximal ascending colon. At laparotomy, a localized tumor about 5 cm in diameter was located in the proximal portion of the ascending colon. The operation was made according to the ileoceal resection. On the macroscopic examination of the resected specimen, a small hole penetrating into the subserosa of the ascending colon was noticed and a tumor measuring approximately 3 x 1.2 x 1 cm was located under the hole. A female worm, Trichuris trichiura, was found to be harbored in the adjacent site of the lesion. Histopathologic examination revealed granulomatous tissue reaction due to penetrating of Trichuris trichiura. The patient is in good health now 20 months after operation.
pancreatic transplantation is the most effective therapy of advanced diabetes mellitus. However, the problem is whether the cadaver pancreas can be used as a donor, because the living pancreas cannot be used as a donor from an anatomical standpoint. In case of the cadaver pancreas another problem is coming up that the pancreas proceeds to rapid autolysis. So, brain death is recommended as the most available condition for this transplantation. In this study we investigated the viability of the cadaver pancreas from decapitated rats preserved by the cold perfusion method. The results obtained were as follows: 1) The perfusing time affected the ratio of degenerative islets/normal islets. A large number of degenerative islets appeared with long perfusion time. 2) The cold (4 degrees C) perfusion method could preserve cadaver pancreas for 5 hours. 3) Insulin-secretion of cadaver pancreatic islets preserved for 5 hours under cold perfusion was 60% or more of that of normal pancreatic islets. 4) Three hundred islets from cadaver pancreas preserved for 5 hours under cold perfusion were transplanted into the portal vein of streptozotocin-induced diabetic rats. Four of these 11 rats recovered from diabetic state and maintained the non-diabetic state for 20 weeks after transplantation.
Pancreatic islet cells of rats obtained by the collagenase digestion method were preserved from 7 to 10 days at -80 degrees C in a deep freezer or at -196 degrees C in liquid nitrogen with Dulbecco modified Eagle's medium, supplemented with 10% or 20% DMSO (dimethyl sulfoxide); thawing was performed in a 37 degree C water bath. Cryopreserved islets were morphologically almost intact, and possessed approximately 50% of the insulin secretion activity of the control groups. About 300 pancreatic islets preserved at -196 degrees C with 20% DMSO were transplanted into the portal veins of streptozotocin-induced diabetic rats. Rats recovered from the diabetic state, and the normalized condition was maintained up to 20 weeks, although 4 weeks were needed before blood and urine glucose reached normal levels after transplantation. Intact B cells were found in the transplanted islet cell masses in the liver of the recipients, but B cells of the recipient's pancreases (streptozotocin-treated rats) showed a marked decrease, as well as degenerative changes.
UNLABELLED: Islets of Langerhans were isolated from the adult wistar rat by means of the collagenase method and cultivated in an incubator at a temperature of 37 degree Celsius and with a mixture of 95% air and 5% CO2. With that each two of the islets were put into every drill hole of multi-dish trays. 1 ml Eagle medium modified by Dulbecco with admixtures of 20% foetal calf serum, 100 microgram/ml Streptomycin and 100 u/ml Penicillin G was the nutrient medium. This medium was exchanged every third day and the released insulin quantity was measured by a radio immunologic test (Phadebas insulin test). RESULTS: 1. The insulin quantity in the nutrient medium runs to 1097 to 1434 microu/ml two islets if a change took place every third day during an 80 days duration of the culture. 2. The cultivated islets had a demonstrable reactivity of the insulin secretion to glucose and glucagon. 3. Diabetic rats with transplants of nearly 400 cultivated islets recover from diabetic state within one week after transplantation and keep healthy for 8 weeks.