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Biomedical subjects

Y Ku

Publications and source records attributed to Y Ku.

At least 109 records · Page 6Linked to original sources

Evidence that portal vein decompression improves survival of canine quarter orthotopic liver transplantation.

The minimum graft volume still remains unclear in reduced-size liver transplantation (RLT). This study reports the improved survival of canine RLT using a quarter graft with the aid of a portahepatic vein shunt (PHVS). In beagles, the donor liver was reduced to the right lateral and caudate lobes (quarter graft) with or without provision of PHVS, and transplanted orthotopically in the recipient. The PHVS was established by an end-to-end anastomosis of the portal vein branch and the hepatic vein in the resected left lateral lobe. Liver chemistries including arterial blood ketone body ratio (AKBR) were serially measured during and after surgery. All seven animals with PHVS survived more than 3 days (mean +/- SD; 5.3 +/- 1.7 days), whereas all six without PHVS died within 3 days (1.8 +/- 0.8 days, P < 0.01). Portal vein pressures immediately after recirculation in animals with and without PHVS were 8.5 +/- 1.2 mmHg and 16.9 +/- 3.1 mmHg, respectively (P < 0.01). Regardless of the presence or absence of PHVS, AKBR dropped to a level lower than 0.7 during the anhepatic period and returned promptly to above 1.0 as early as 30 min after recirculation. Thereafter, the AKBR values in animals with PHVS remained higher than 1.0, whereas those in animals without PHVS showed a progressive decrease, showing a statistically significant difference between the two groups after 12 hr (P < 0.05). Graft function, as assessed by AKBR, was well correlated with survival and other liver chemistries. These results indicate that, in an extreme RLT, portal hypertension is a risk factor predisposing to graft failure, most likely by increasing microvascular injury after recirculation.

Animals↗

Heart preservation using a cavitary two-layer (University of Wisconsin solution/perfluorochemical) cold storage method.

To reduce cold ischemic injury of the heart by supplying sufficient oxygen to the heart during preservation, we have developed a new cavitary, two-layer (University of Wisconsin solution/perfluorochemical) cold storage method. The oxygenation of the heart during preservation by this method allows ATP production within the graft and makes it possible to extend preservation time up to 48 hr in the heterotopic rat heart transplant model.

Adenosine↗

Spontaneous splenic rupture during the course of a rubella infection: report of a case.

We report herein the case of a 26-year-old man who suffered a spontaneous splenic rupture during the course of a rubella infection. Initially, he presented with a high fever accompanied by a skin rash extending from the body trunk to the extremities and was admitted to hospital 3 days after onset for sudden upper abdominal pain radiating to both shoulders. On admission, he was pale and sweating with hypotension. An abdominal ultrasonographic study revealed a collection of fluid in the perisplenic space and exploratory laparotomy confirmed an intraabdominal hemorrhage from a ruptured spleen. The patient was treated by splenectomy and recovered uneventfully. The excised spleen was found to be moderately enlarged with a denuded capsule. Because the patient had no history of any external trauma and a positive serological test for rubella, we concluded that rubella contributed to the spontaneous splenic rupture in this case.

Adult↗

Furan fatty acids determined as oxidation products of conjugated octadecadienoic acid.

The objective of this study was to identify oxidation products of conjugated linoleic acid (CLA), a series of octadecadienoic acids with conjugated double bonds, which have been reported to have antioxidant and anticarcinogenic properties. Reference materials of CLA were oxidized in different concentrations of water/methanol; for example, 0.5 g octadecadienoic acid was dissolved in 50 mL methanol, and 100 mL water was added; this suspension was heated at 50 degrees C and continuously aerated. Aliquots of 5 mL were taken over time, extracted with ether, treated with diazomethane and examined by gas chromatography/mass spectrometry and/or gas chromatography with flame-ionization detection. Products identified included the following furan fatty acids (FFAs): 8,11-epoxy-8,10-octadecadienoic; 9,12-epoxy-9,11-octadecadienoic; 10,13-epoxy-10,12-octadecadienoic; and 11,14-epoxy-11,13-octadecadienoic. Conjugated dienes should be considered as a possible source of FFAs, and CLA may have products common to furans in their overall oxidative scheme.

Anticarcinogenic Agents↗

Clinical pilot study on high-dose intraarterial chemotherapy with direct hemoperfusion under hepatic venous isolation in patients with advanced hepatocellular carcinoma.

BACKGROUND: We recently developed a novel system of direct hemoperfusion under hepatic venous isolation in an attempt to achieve high-dose intraarterial chemotherapy for patients with malignant liver tumors. We report here the results of treatment of these patients with advanced hepatocellular carcinoma. METHODS: Adriamycin (100 to 150 mg/m2) was administered into the hepatic artery of 15 patients, under conditions of extracorporeal drug elimination by direct hemoperfusion under hepatic venous isolation. Hepatic venous isolation was accomplished mainly by the double-balloon technique with an occlusion catheter and a balloon catheter. The isolated hepatic venous blood was filtered by direct hemoperfusion and pumped to the left axillary vein. RESULTS: During 5 minutes of adriamycin infusion, the mean drug extraction ratios of the direct hemoperfusion filters were 91% +/- 9% (mean +/- SD). The amount of drug removed by the system was 26.4% +/- 16.0% of the amount of drug administered. Two patients died, one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Other side effects included hemolysis related to the system of hemoperfusion (87%), chemical hepatitis (80%), leukopenia less than 3000/mm3 (67%), alopecia (33%), and nausea and vomiting (20%). Nine (64%) of 14 evaluable patients had objective tumor responses, with a median duration of response of 6.2 months. CONCLUSIONS: This approach offers an effective therapeutic option for patients with advanced hepatocellular carcinoma.

Adult↗

A new technique for pancreaticogastrointestinal anastomosis without suturing the pancreatic parenchyma.

BACKGROUND: In an attempt to lessen the incidence of pancreatic fistula and the disruption of pancreatic anastomosis after pancreatoduodenectomy, we have developed a new technique for pancreaticogastrointestinal anastomosis that consists of pancreatectomy using the ultrasonic dissector and implantation of the pancreatic duct into the gastrointestinal tract without suturing the pancreatic parenchyma. The purpose of this study is to evaluate the safety and reliability of this new technique in a canine model of pancreaticogastrostomy and pancreaticoduodenostomy using 10 beagle dogs. STUDY DESIGN: Canine pancreas was resected using the ultrasonic dissector. In the distal pancreas, a 1-cm long stump of the main pancreatic duct was freed and the other smaller pancreatic ducts were skeletonized and securely ligated. The main pancreatic duct was implanted into the stomach or the duodenum and fixed to the seromuscular layer with purse-string sutures without suturing the pancreatic parenchyma. RESULTS: There was no anastomotic leakage, signs of peritonitis, or abscess formation, and the pancreas was grossly normal in appearance seven days after operation. Histologic examination of the specimens harvested 30 days after operation revealed good connective tissue union between the pancreas and the gastric or duodenal wall, and good mucosal continuity between the pancreatic duct and the stomach or duodenum. CONCLUSIONS: This new technique is simple, safe, and reliable, and is recommended as an alternative method for restoring pancreaticogastrointestinal continuity after pancreatoduodenectomy.

Anastomosis, Surgical↗

[The effect of percutaneous hepatic venous isolation and charcoal hemoperfusion for high-dose chemotherapy for hepatoma].

We herein report the efficacy of percutaneous high-dose chemotherapy under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) in the treatment of hepatoma patients. This study included 23 patients with bilobar multiple intrahepatic metastases and 1 patient with high risk for recurrence after hepatectomy. All patients received adriamycin at doses ranging from 60-150 mg/m2 through the hepatic artery. Sixteen patients had HVI.CHP by the double-balloon technique, while a recent 8 patients had the single catheter technique using a 4L.2B catheter; 4 of these 8 patients had repeated treatment. Except for two early patients with hepatic arterial thrombosis and necrotizing pancreatitis, there was no lethal complication, and quality of life after treatment was remarkably improved in patients treated by the single catheter technique. Among 22 evaluable patients, 3 had CR and 11 had PR, yielding a response rate of 63%. Mean survival duration was prolonged to 13 months in responders, against only 5 months in nonresponders. In conclusion, HVI.CHP was highly effective for advanced hepatoma patients and the single catheter technique facilitated a repeated high-dose intraarterial chemotherapy, which may offer a possibility of complete remission even in highly advanced cases.

Carcinoma, Hepatocellular↗

[Pharmacokinetic comparison of intraarterial and intraportal infusion of adriamycin in regional chemotherapy of the liver].

We investigated the adriamycin (ADR) pharmacokinetics following intraarterial and intraportal infusion under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). HVI.CHP was used to measure the first-pass amount of adriamycin through the liver and to reduce hepatic re-entry of the drug. Beagles underwent a 10-min ADR infusion (1 mg/kg) either through the hepatic artery (group I, n = 5) or the portal vein (group II, n = 5) under a 20-min HVI.CHP. During HVI.CHP, the hepatic venous flow rate and plasma ADR levels in prefilter (hepatic venous level), postfilter and peripheral blood were serially measured. Based on these measurements, the hepatic extraction ratio (HER) of ADR was calculated. Areas under the time-concentration curves of prefilter levels in groups I and II were 6.1 +/- 1.6 and 16.9 +/- 5.0 micrograms.min/ml, respectively, showing a significant difference between two groups (p < 0.01). On the contrary, HER of group I (81.2%) was significantly higher than that of group II (47.2%, p < 0.01). These results indicate that intraarterial infusion of ADR is superior to intraportal infusion in terms of local drug delivery to the liver and systemic drug toxicities.

Animals↗

[Pharmacokinetic evaluation of complete infrarenal inferior vena caval isolation and charcoal hemoperfusion for intra-arterial chemotherapy of pelvic tumors].

Regional chemotherapy for malignant pelvic tumors is disappointing due to the poor tumor response and dose-limiting systemic toxicity. This study was designed to determine whether a novel venous isolation-charcoal hemoperfusion system could limit systemic exposure to chemotherapeutic agents after regional arterial infusion. Adriamycin (2 mg/kg) was continuously administered in the internal iliac arteries of beagles under complete isolation of the infrarenal inferior vena cava and extracorporeal charcoal hemoperfusion (IVCI.CHP). Control beagles received adriamycin at the same dosage without IVCI.CHP. Plasma adriamycin concentrations were measured in the left carotid artery (systemic level) at intervals of up to 40 minutes after the start of drug infusion. In animals with IVCI.CHP, the drug levels were also determined at the inlet and outlet of a CHP filter. The mean drug extraction ratios by the CHP filter averaged 88%. As a result, animals with IVCI.CHP showed a significant reduction in systemic drug levels at all measuring time points compared to controls. The peak systemic levels of adriamycin were 0.8 +/- 0.1 and 2.3 +/- 0.8 micrograms/ml, respectively, in IVCI.CHP and control animals (p < 0.01). IVCI.CHP accomplished a significant reduction in systemic exposure to adriamycin after iliac arterial infusion. This novel system will allow regional delivery of high-dose cytotoxic agents with little systemic toxicity for pelvic tumors.

Animals↗

[A case of malignant fibrous histiocytoma treated with intraarterial chemotherapy under complete venous isolation and charcoal hemoperfusion].

Herein reported is a case with malignant fibrous histiocytoma (MFH) at the left elbow treated successfully with intraarterial chemotherapy under complete brachial venous isolation and charcoal hemoperfusion (BVI-CHP). A 56-year-old man was admitted to our institution because of local recurrence at the left elbow 6 months after extended local resection combined with systemic chemotherapy. We treated the patient with a 15-min intraarterial infusion of adriamycin (100 mg/body) and cisplatin (30 mg/body) under a concomitant 30-min BVI-CHP. Two weeks after the first treatment, he received a repeated intraarterial infusion of adriamycin (80 mg/body) and cisplatin (50 mg/body) under BVI-CHP. The tumor became necrotic one week after the first treatment, resulting in 60% reduction in tumor diameter. In addition, angiography demonstrated a remarkable shrinkage of the tumor stain. Despite repeated intraarterial high-dose infusions of chemotherapeutic agents, systemic toxicities, such as leukopenia, nausea/vomiting and alopecia, were not observed. These results indicate that this approach offers a novel therapeutic option for malignant tumors in the extremities.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of multiple liver metastases of breast cancer treated successfully with high-dose intraarterial chemotherapy under hepatic venous isolation and charcoal hemoperfusion (HVI-CHP)].

The patient was a 53-year-old woman who underwent a standard radical mastectomy for right breast cancer five years ago and was recently referred to our hospital with a complaint of abdominal fullness. Systemic chemotherapy (CMFS) was performed based on the diagnosis of multiple liver metastases of the breast cancer, but its effect was unsatisfactory. In this case, we gave her high-dose intraarterial chemotherapy under HVI.CHP for metastatic liver tumors. Although slight elevation of serum GOT and GPT levels and leucopenia (1,800/mm3) were observed, alopecia did not occur throughout the posttreatment course. The levels of tumor markers including CEA, NCC-ST439 and CA15-3 showed remarkable reductions; CEA (ng/ml): 18.4-->3.0, NCC-ST439 (U/ml): 33.0-->2.4, CA15-3(U/ml): 137.9-->26.3. Abdominal CT scan after the treatment demonstrated remarkable regression of liver metastases, showing a partial response (volume reduction: 61%). In conclusion, HVI.CHP achieved a significant reduction in systemic drug exposure and allowed dose intensification of adriamycin during intraarterial chemotherapy. Therefore, we consider that high-dose intraarterial chemotherapy under HVI.CHP offers an effective therapeutic option for multiple liver metastases of the breast cancer.

Antibiotics, Antineoplastic↗

5-Fluorouracil attenuates an oncostatic effect of melatonin on estrogen-sensitive human breast cancer cells (MCF7).

The pineal hormone, melatonin, has been reported to have an inhibitory effect on the cell growth of human breast cancer. We have now assessed the interaction of melatonin with 5-fluorouracil (5-FU) on estrogen-sensitive MCF7 and estrogen-insensitive HBC4 cell lines. Melatonin inhibited MCF7 cell growth dose-dependently, reaching a maximum inhibition of growth of 39% that of control at a concentration of 0.3 nM (this is about equivalent to the physiological concentration of melatonin secreted at 0200 h in humans). 5-FU also demonstrated an inhibitory effect on MCF7 cell growth and a maximal inhibition of growth by 24% was acquired at a concentration of 500 ng/ml. By contrast, the inhibitory effect of melatonin was reduced by the co-administration of 5-FU, independently of 5-FU concentration. Melatonin and/or 5-FU exhibited no effect on HBC4 cells. This preliminary study indicates that 5-FU should be handled with care for treatment of estrogen sensitive-breast cancer.

Breast Neoplasms↗

Role of adenosine in preservation by the two-layer method of ischemically damaged canine pancreas.

The purpose of this study was to clarify the role of adenosine in preservation of ischemically damaged pancreas by the two-layer (Euro-Collins solution [EC]/perfluorochemical [PFC]) method using a canine model. Twenty-four-hour preservation of the pancreas graft subjected to 60-min warm ischemia was successful by the two-layer (EC with adenosine/PFC) method (4/5, 80%), but neither simple cold storage in EC (0/5, 0%), nor EC with adenosine (1/5, 20%), nor the two-layer (EC/PFC) method (0/3, 0%) was successful. Tissue ATP concentrations at the end of preservation by the two-layer (EC with adenosine/PFC) method were significantly higher compared with the two-layer (EC/PFC) method (7.23 +/- 2.17 vs. 1.56 +/- 0.40 mumol/g dry weight, P < 0.01). Studies with [2-3H]adenosine demonstrated that only part of adenosine was converted to inosine, hypoxanthine, and adenine, whereas the remainder was incorporated into adenine nucleotides in the pancreas graft. In addition, hypoxanthine, inosine, and adenine did not substitute for adenosine. We conclude that provision of adenosine to ischemically damaged pancreas during preservation by the two-layer (EC/PFC) method allows ATP synthesis within the graft via direct phosphorylation of adenosine. Metabolic processes vital to repair damaged cells and maintain cellular integrity can be maintained, which makes it possible to preserve ischemically damaged pancreas.

Adenosine↗