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Y Ku

Publications and source records attributed to Y Ku.

At least 127 records · Page 7Linked to original sources

Protective effect of preservation of canine pancreas by the two-layer (University of Wisconsin solution/perfluorochemical) method against rewarming ischemic injury during implantation.

Rewarming ischemia during implantation severely compromises posttransplant pancreas graft survival because the graft has already been subjected to warm and cold ischemia before implantation. The purpose of this study was to examine whether preservation of the pancreas graft by the two-layer method ameliorates rewarming ischemic injury of the graft during implantation using a canine model. After flushing with cold University of Wisconsin solution (UW), the pancreas grafts were preserved by the two-layer (UW/perfluorochemical [PFC]) method (group 1) or simple cold storage in UW (group 2) for 24 hr and then autotransplanted. In control, the pancreas grafts were flushed out with cold UW and immediately autotransplanted without preservation (group 3). After completion of vascular anastomosis, vascular clamp was not released until 90, 120, or 150 min of rewarming ischemia, including anastomosis time, had elapsed. After 90 min of rewarming ischemia, graft survival rates were 5/5, 100%, 5/5, 100%, and 5/5, 100%, in groups 1, 2, and 3, respectively. After 120 min, all the grafts in groups 2 and 3 failed (0/5, 0%, and 0/5, 0%, respectively); however, all the grafts in group 1 survived (5/5, 100%). Even after 150 min, 1 of 3 grafts in group 1 survived (1/3, 33%). After 24 hr preservation, tissue ATP levels of the grafts in group 1 were about 2-fold the reference values before harvesting (8.23 +/- 0.72 vs. 4.44 +/- 0.49 mumol/g dry weight, P < 0.05) and significantly higher compared with group 2 (8.23 +/- 0.72 vs. 1.76 +/- 0.52 mumol/g dry weight, P < 0.01). After 120 min of rewarming ischemia, tissue ATP levels in group 1 were 84% of the reference values and significantly higher compared with group 2 (3.75 +/- 0.25 vs. 1.57 +/- 0.48 mumol/g dry weight, P < 0.05). Two hours after reperfusion, ATP levels in group 1 were 42% of reference values but significantly higher compared with group 2 (1.86 +/- 0.36 vs. 1.03 +/- 0.18 mumol/g dry weight, P < 0.05). We conclude that the two-layer (UW/PFC) method ameliorates rewarming ischemic injury of the pancreas graft during implantation by increasing tissue ATP contents during preservation and consequently maintaining tissue ATP levels during implantation.

Adenosine↗

Direct hemoperfusion under infrahepatic inferior vena caval isolation for the intraarterial chemotherapy of pelvic tumors.

A new simple technique consisting of direct hemoperfusion under infrahepatic inferior vena caval isolation for intraarterial chemotherapy of pelvic tumors is herein described. The inferior vena cava is occluded at the infrahepatic level by means of balloon inflation using a balloon-tipped catheter (16F), which is placed through the right greater saphenous vein. The isolated infrahepatic vena caval blood is withdrawn by a centrifugal pump through a catheter (16F) in the contralateral greater saphenous vein and is filtered by direct hemoperfusion during intraarterial infusion of anticancer drugs. Venous reentry is provided by the central lumen of the balloon-tipped catheter. This procedure was used sequentially on two different occasions to treat a patient with an extensive pelvic tumor. Good hemodynamic stability and a reduction of the systemic drug toxicities were confirmed in both trials. Therefore, we believe that this technique is technically feasible and highly effective in reducing systemic toxicities during high-dose intraarterial chemotherapy for pelvic tumors.

Aged↗

Effect of cold aerobic perfusion on nonparenchymal cell viability of rat livers.

We investigated the effect of oxygen supply on hepatic cellular viability during cold perfusion storage of rat livers. A perfluoro-N-methyldecahydroisoquinoline (FMIQ) emulsion is used as an oxygen carrier. The composition of the perfusate containing 20 w/v% FMIQ is essentially the same as the University of Wisconsin (UW) solution except for the exclusion of hydroxyethyl starch. Rat livers were perfused at 4 degrees C for up to 24 h with either UW solution (group I, oxygenated; group II, unoxygenated) or FMIQ solution (group III, oxygenated; group IV, unoxygenated). After perfusion storage, the livers were reperfused with warm (37 degrees C) oxygenated or cold (4 degrees C) unoxygenated Krebs-Henseleit bicarbonate buffer, and nuclear trypan blue uptake was measured as the index of cell death. With warm oxygenated reperfusion, there remained less than 2% noviable parenchymal cells up to 24 h, regardless of perfusate or oxygenation. In UW-perfused livers, the proportion of nonviable nonprenchymal cells (NPC) increased progressively regardless of oxygenation, the values in groups I and II in the periportal field at 24 h being 39.9 +/- 4.7% (mean +/- SD) and 36.5 +/- 4.2%, respectively. By contrast, in FMIQ-perfused livers, dye uptake by NPC was significantly reduced with oxygenation (16.9 +/- 5.7% and 39.4% +/- 9.1% at 24 h in groups III and IV; P < 0.001). With cold unoxygenated reperfusion, livers in groups I, II, and IV showed a significant decrease of nonviable NPC, while those in group III showed no significant changes. These data indicate that oxygen supply during perfusion storage of the liver may ameliorate lethal injury to NPC precipitated during reperfusion.

Adenosine↗

Metabolic intervention to affect canine pancreas recovery following ischemia during preservation by the two-layer method.

We have demonstrated that a high adenosine triphosphate (ATP) level in a canine pancreas during preservation by the two-layer method is an important determinant for the ultimate success of pancreatic transplantation. In this study, we investigated (a) the effect of factors that seemed to have an influence on energy metabolism in the canine pancreas at the tissue ATP level and (b) graft viability during preservation by the two-layer method. ATP tissue concentration was determined by high-performance liquid chromatography and graft viability was assessed on the basis of survival rate following autotransplantation. First, the pancreas was harvested from either 72-h-fasted (n = 5) or fed dogs (n = 5) and preserved by the two-layer Euro-Collins solution (EC)/perfluorochemical (PFC) method for 24 h. All the pancreatic grafts were viable in both fed and fasted groups. There was also no significant difference in ATP tissue concentration between the two groups (7.48 +/- 0.55 vs. 7.03 +/- 0.74 micromol/g dry weight, NS). Second, the pancreatic grafts subjected to 60 min of warm ischemia were preserved by either the two-layer (EC/PFC) or (EC + adenosine/PFC) method for 24 h. Without adenosine, ATP tissue concentration did not recover (1.62 +/- 0.26 after warm ischemia vs. 1.56 +/- 0.40 micromol/g dry weight after preservation, NS) and all the pancreatic grafts failed. However, provision of adenosine led to restoration of ATP tissue levels (1.90 +/- 0.53 vs. 7.23 +/- 2.17 micromol/g dry weight, P < 0.01) and four of five grafts functioned immediately and maintained normoglycemia after transplantation. These results clearly demonstrated that the nutritional state of the pancreatic graft before procurement had no influence on ATP tissue level as well as graft viability during 24-h preservation by the two-layer method. On the other hand, provision of adenosine during 24-h preservation enhanced ATP synthesis of the pancreatic tissue, thereby improving viability of the ischemically damaged pancreas.

Adenosine↗

Difference in energy metabolism between fresh and warm ischemic canine pancreases during preservation by the two-layer method.

We have demonstrated that adenosine triphosphate (ATP) is synthesized within a canine pancreas during preservation by the two-layer method and there is a direct correlation between a high ATP tissue level and good posttransplant outcome. The purpose of this study was to examine the difference in energy metabolism between fresh and warm ischemic pancreases during preservation by this method. First, fresh pancreases were preserved with simple cold storage in Euro-Collins solution (EC; group 1A), or by the two-layer method using EC (group 1B), EC with 2,4 dinitrophenol (DNP; group 1C), an uncoupler of oxidative phosphorylation, or modified EC (ECM; group 1d), which contained mannitol in place of glucose for 48 h. ATP tissue concentrations in group 1B were significantly higher than in group 1A (7.91 +/- 1.21 vs. 1.21 +/- 0.31 micromol/g dry weight, P < 0.01) but almost equal to group 1d (7.91 +/- 1.21 vs. 7.59 +/- 0.97 micromol/g dry weight, NS). DNP (group 1C) caused a significant decrease in tissue ATP levels in group 1A (0.61 +/- 0.07 vs. 7.91 +/- 1.21 micromol/g dry weight, P < 0.01). Second, pancreases subjected to 60 min of warm ischemia were preserved by simple cold storage with EC (group 2A) or the two-layer method using EC (group 2B) or EC with adenosine (group 2C) for 24 h. ATP tissue levels in groups 2A and 2B after preservation were 1.40 +/- 0.46 and 1.56 +/- 0.40 micromol/g dry weight and graft survival rates were 0/5 (0%) and 0/3 (0%), respectively. However, tissue ATP levels in group 2C after preservation were significantly higher compared with the value before preservation (7.23 +/- 2.17 vs. 1.90 +/- 0.53/g dry weight, P < 0.01) and graft survival rate was 4/5, 80%. Other nucleosides, hypoxanthine, inosine, and adenine did not substitute for adenosine. In addition, studies with [2-3 H] adenosine demonstrated that almost all of the adenosine was converted to adenine nucleotides. This study clearly demonstrated that fresh grafts synthesize ATP mainly via mitochondrial oxidative phosphorylation using endogenous substrates. However, after significant warm ischemia, pancreases produce ATP mainly via direct phosphorylation of exogenous adenosine during preservation by the two-layer method.

2,4-Dinitrophenol↗

[A new method of high-dose intraarterial chemotherapy of the pancreas using direct hemoperfusion (DHP) under portal venous isolation (PVI)].

Surgical resection for pancreatic cancer is severely limited by the extent of the disease at the time of diagnosis. Chemotherapy has been the treatment of choice for unresectable cases. We developed a new method of intraarterial chemotherapy for pancreatic body and tail cancers using direct hemoperfusion (DHP) under portal venous isolation (PVI). Adriamycin (ADR, 3 mg/kg) was infused into the splenic arteries of mongrel dogs for 5 min after clamping off blood flow to the stomach and the duodenum. In group A (n = 5), this was simply done, and in group B (n = 5) the portal venous blood was isolated by clamping at the porta hepatis and pumped through the DHP circuit to the jugular vein for 20 min from the start of drug infusion. The peak systemic level (microgram/ml) of group B (0.78 +/- 0.03) was significantly reduced by PVI.DHP as compared to that of group A (3.49 +/- 1.15, P < 0.01). The pancreatic tissue levels (microgram/g. tissue) 30 min after drug infusion of group A (61.2 +/- 13.4) were slightly lower than those in group B (88.9 +/- 27.8), although not statistically significant. However, tissue levels of group B in the liver (27.3 +/- 9.2) and heart (1.8 +/- 0.8) were significantly lower than those of group A (liver; 52.3 +/- 18.5, heart; 4.9 +/- 0.6, P < 0.05). In conclusion, PVI.DHP achieved a significant reduction in systemic drug exposure during intraarterial chemotherapy. Therefore, we consider that this system will allow dose escalation of ADR during intraarterial chemotherapy for pancreatic body and tail cancers.

Animals↗

[Comparison of transarterial and transportal heating bypass in canine regional liver hyperthermia].

We compared the efficacy of transarterial heating (group I; n = 5) with transportal heating (group II; n = 3) in regional liver hyperthermia. In beagles, the femoro-hepatic arterial (FA-HA) or the femoro-portal (FV-PV) heating bypass was made. Mean bypass flow rates in groups I and II were set at 120 ml/min and 260 ml/min, respectively, simulating either actual hepatic arterial flow or portal flow rates. Bypass heating was initiated by soaking a warmer coil into the water bath kept at 45 degrees C and maintained for 60 min. The temperature of the inflow line in groups I (44.4 +/- 0.1 degrees C) and II (44.5 +/- 0.1 degrees C) became similar 5 min after the start of heating. The liver parenchymal temperature of group I promptly reached 42.0 +/- 0.9 degrees C at 30 min and could be easily controlled at a range of 42.0-42.5 degrees C thereafter. However, despite a higher heated blood flow rate in group II, the liver parenchymal temperature remained 41.1 +/- 0.1 degrees C at 60 min (p < 0.01, vs. group I). The highest rectal temperature of group I was 38.9 +/- 0.8 degrees C, while that of group II was 40.5 +/- 0.2 degrees C (p < 0.05). In conclusion, the effect of transarterial heating was superior to that of transportal heating, indicating the different thermokinetics in regional liver hyperthermia in the two methods.

Animals↗

[An experimental study on liver hyperthermia using intraperitoneal hyperthermic perfusion (IPHP)].

We evaluated the efficacy of intraperitoneal hyperthermic perfusion (IPHP) in regional hyperthermia of the liver. In white rabbits, an infusion catheter and a drainage catheter were placed in the Douglas pouch and upper abdominal cavity, respectively. Warm saline (46-48 degrees C) was infused into the abdominal cavity at a flow rate of 30-60 ml/min. The temperature was continuously monitored at seven measuring points including water bath, peritoneal inflow line, abdominal cavity, liver parenchyma, portal vein, rectum and esophagus. Temperature of the inflow line was maintained at 46-48 degrees C throughout the course. Temperature of the abdominal cavity reached 42.0-42.6 degrees C 30 minutes after the start of IPHP. The temperature of the portal vein reached 40.9 degrees C and 41.8 degrees C at 30 and 60 minutes, respectively. Liver parenchymal temperature increased to 41.5 degrees C and 42.1 degrees C at 30 and 60 minutes, respectively, indicating effective heating of the liver. On the other hand, the temperatures of the rectum and esophagus remained less than 39.2 degrees C and 40.4 degrees C throughout the course. Therefore, we consider that IPHP will be a simple and effective method for the performance of liver hyperthermia.

Animals↗

[A case of hepatic atrophy by irradiation].

A 44-year-old woman was treated with 60Co irradiation (total dose, 6000 rads) focused on the right side porta hepatis under the diagnosis of cholangiocarcinoma in 1975. Seventeen years after the treatment, she was admitted to our institution because of dull pain at right hypochondriac region. Abdominal CT demonstrated an extreme hepatic atrophy and tumor mass in the right lobe of the liver. In November, 1991 right tri-segmentectomy was performed under the diagnosis of hepatocellular carcinoma. Laparotomy revealed the extreme atrophy of the right lobe and associated hypertrophy of the left lobe of the liver. In this case radiation hepatitis occurred after irradiation to the liver and it was followed by the extreme hepatic atrophy as a long term effect of high dose irradiation on the liver.

Adult↗

[The experimental studies on concomitant occlusion of the superior mesenteric artery during intraarterial chemotherapy of the liver].

We investigated the effect of temporary occlusion of the superior mesenteric artery (SMAO) on the hepatic tissue concentration of anticancer drugs in hepatic artery infusion. Adriamycin (ADR: 1 mg/kg weight) was continuously administered into the hepatic artery for five minutes in dogs. Depending on the use and method of vascular occlusion, animals were allocated into five groups and hepatic tissue ADR levels were determined: Group I, SMAO; Group II, no vascular occlusion; Group III, occlusion of the common hepatic artery (CHAO); Group IV, combined SMAO and CHAO; Group V, occlusion of the portal vein. The hepatic tissue ADR level at 10 minutes was significantly higher in Group I than those in Group II and III. The tissue ADR level in Group IV and V tended to be slightly higher than in Group I, although there is no statistically significant difference. These results indicate that SMAO may provide a useful means of increasing local drug level during regional chemotherapy of the liver.

Animals↗

[An experimental study on a new technique of regional liver hyperthermia using femoro-hepatic arterial thermal bypass].

This study was undertaken to evaluate the efficacy of a new method using the femoro-hepatic arterial (FA-HA) thermal bypass for regional liver hyperthermia. Using mongrel dogs (n = 8), a 12 Fr catheter was introduced into the abdominal aorta through the right femoral artery. A hepatic arterial catheter (8 Fr) was placed through the gastroduodenal artery. These catheters were connected to a system containing a centrifugal pump and a heat exchanger. The heat exchanger consists of warmer coils and a water bath kept at a temperature of 47 degrees C. The bypass was run at an average blood flow rate of 153 +/- 33 (mean +/- SD) ml/min. The temperature was continuously monitored at four measuring points, including the water bath, the inflow blood, the liver parenchyma and the rectal cavity. The temperature of the liver parenchyma promptly reached 40.0 +/- 1.7 degrees C as early as 5 minutes and reached its highest value of 42.8 +/- 0.8 degrees C 30 minutes after the start of hyperthermia. The rectal temperature was 39.3 +/- 1.2 degrees C at 30 minutes. The temperature of the liver parenchyma (38.1 +/- 1.4 degrees C) became similar to that of the rectum (38.1 +/- 1.3 degrees C) 30 minutes after the end of hyperthermia. These results indicate that the FA-HA thermal bypass is a simple and highly effective method for the performance of regional liver hyperthermia.

Animals↗

[Serum beta-N-acetyl hexosaminidase as a new marker of graft viability in canine orthotopic liver transplantation].

We investigated the correlation between graft viability and serum beta-N-acetyl hexosaminidase (beta-NAH), a well characterized circulatory lysosomal enzyme degraded specifically by the Kupffer cell. Orthotopic liver transplantation (OLT) was performed in 17 dogs; Group I, 1 hr preservation and survival beyond 3 days; Group II, 1 hr preservation and survival less than 2 days; Group III, 20 hr preservation. Serum beta-NAH was compared with AST and TBA. Serum beta-NAH (nmol/ml/hr) reached the peak values of 611 +/- 125, 1227 +/- 310 and 3952 +/- 685 until 6 hr after reperfusion in groups I, II and III, respectively. AST (IU/L) reached the peak levels of 929 +/- 350, 1581 +/- 396 and 1945 +/- 394 at 24 hr in groups I, II and III, respectively. TBA (mumol/l) reached the peak levels at a time point immediately before reperfusion in group I (37.9 +/- 7.8) and II (42.5 +/- 8.4), whereas prolonged elevation was still continued even after reperfusion in group III. AST gave significant separation only after 24 hr (p < 0.01) between groups I and II and at 15 min (p < 0.01) between groups I and III. In contrast, beta-NAH and TBA showed significant separation between groups I and II at 4 hr (p < 0.01) and between groups I and III at 15 min (p < 0.01). These results suggest that serum beta-NAH is an early, sensitive marker of graft function reflecting both hepatic cellular damage and functional recovery of the reticuloendothelial system.

Animals↗

[Nocturnal infusion of 5-fluorouracil in advanced digestive tract cancer--two case reports].

Two patients, with terminal stage digestive tract carcinoma, are presented who received continuous nocturnal administration of intravenous 5-FU (300 mg/m2/day), between 9:00 pm and 8:00 am for more than 45 consecutive days. They showed improvement in general physical and functional status, and no side effects were observed. The first case is that of a patient with not only an early gastric cancer, but also a nonresectable esophageal cancer. After therapy, complete disappearance of the gastric cancer was noted by endoscopy. The second patient had advanced gastric cancer with carcinomatosis. He received intraperitoneal cisplatinum for intractable ascites without improvement. But after continuous nocturnal 5-FU therapy, a significant reduction in ascites was noted. Two cases did not experience leukopenia and no significant side effects were noted, even in the second patient who received nocturnal 5-FU for 122 days. The therapeutic effects of continuous nocturnal 5-FU administration generally appeared after 20 days, so a prolonged period of time seems to be important.

Adenocarcinoma↗