Biomedical subjects
Publications and source records attributed to Y Iso.
We describe an efficient method for introducing a sulfamoylamino group into the C-2' position of pyrrolidine using the Mitsunobu reaction. S-4661, its N-methyl analogues and stereoisomers were synthesized using this method and their structure-activity relationships were investigated.
A 61-yr-old man underwent Billroth I gastrectomy for an advanced cancer in the corpus of the stomach. On the first postoperative day, fresh bile discharged from the penrose drains, which had been placed in Winslow's foramen, and the volume of bile discharge subsequently increased. Leakage from the gastroduodenal anastomosis was excluded by gastroduodenography. Exploratory relaparotomy showed bile peritonitis with much more bile retention in the left subphrenic space. The origin of bile leakage could not be traced despite close examination of all the extrahepatic biliary tract and the liver surface. Intraoperative cholangiography through the cystic duct after cholecystectomy revealed that the bile leakage originated from an aberrant bile duct present in the free edge of the left triangular ligament (appendix fibrosa hepatis), which had been unintentionally cut at the primary operation. Knowledge of this anatomical structure is important and proper ligation is recommended when dissecting the appendix fibrosa hepatis to avoid postoperative bile peritonitis and the need for a relaparotomy.
A 62-year-old man having advanced gastric carcinoma with extended lymph node metastases was successfully treated by a palliative gastrectomy and 6 courses of sequential methotrexate/5-fluorouracil therapy. No side effects were observed, and all enlarged abdominal lymph nodes disappeared. The complete response has continued for 11 months after the initial treatment.
We report here the operative findings, the incidence of successful laparoscopic treatment, and the perioperative complications in patients with nonvisualized gallbladder on drip infusion cholangiography (DIC). Eighty-five patients with a nonvisualized gallbladder on DIC were entered into the study. None of the patients had a minimal adhesive gallbladder; 51 to 85 patients (60.0%) had moderate adhesive gallbladders, and 34 (40.0%) had severely adhesive ones. The rate of successful laparoscopic treatment, including laparoscopy-assisted abdominal surgery, was 97.6% (83 of 85 patients). Perioperative complications occurred in only three patients (3.5%), and there were no deaths related to the operation. Thus, when patients with a nonvisualized gallbladder on DIC undergo laparoscopic cholecystectomy, meticulous procedures must be carried out; however, as the rate of successful laparoscopic treatment is high, cholecystectomy under laparoscopy is feasible for experienced surgeons.
Devascularization of the lower esophagus and the upper stomach is one method of treating patients with clinically significant gastric varices. We describe a new method of laparoscopically-assisted devascularization which has been applied in seven patients with esophagogastric varices. Three of the seven patients had an episode of gastric variceal bleeding, and the remaining four had moderate to large gastric varices with red color signs. The operative procedure was carried out without pneumoperitoneum by using an ordinary forceps and laparoscopic instruments through a small skin incision (3-5 cm); the abdominal wall was elevated with a U-shaped retractor. The operative field was obtained by laparoscopic and direct vision illuminated by laparoscopic light. The procedure time ranged from 100 to 180 minutes with minimal blood loss (70-320 g). No complications were encountered. All patients could be discharged within one week; postoperative pain was minimal and all patients returned to work early. Follow-up (mean 11.4 months) showed no recurrence of gastric varices although, due to an incomplete procedure in two cases, two patients were treated additionally by endoscopic injection of histoacryl.
Laparoscopic distal partial gastrectomy is still technically difficult under conditions of a pneumoperitoneum because of the lack of appropriate techniques and laparoscopic instruments. We describe here a technique of laparoscopy-assisted Billroth I gastrectomy under an abdominal wall-elevating method.
The affinity cross-linking of the delta-opioid receptor in neuroblastoma x glioma NG108-15 cells was undertaken using (3-[125I]iodotyrosyl27)human-beta-endorphin ([125I]beta-endorphin) and disuccinimidyl suberate (DSS) or bis(sulfosuccinimidyl) suberate (BS3) in order to estimate molecular size. Following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, two radioactive bands were observed. Labeling of a major band of 29 kDa diminished in the presence of unlabeled selective delta-opioid agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE), in a concentration-dependent manner, while labeling of a minor band of 58 kDa was hardly affected. The labeling intensity of the 29 kDa band decreased by addition of guanosine 5'-(3-o-thio)triphosphate (GTP gamma S) or by pretreatment of cells with pertussis toxin. These results, taking the molecular weight of covalently bound beta-endorphin (3.6 kDa) into consideration, suggest that the delta-opioid receptor in NG108-15 cell membrane is a 25 kDa protein which is coupled to pertussis toxin-sensitive guanosine triphosphate-binding proteins (G-proteins).
Ninety-six patients with good liver function (Child class A or B) and esophageal varices were randomly assigned to one of three groups given different treatments: endoscopic injection sclerotherapy (n = 32), esophageal transection (n = 32) or distal splenorenal shunt (n = 32). Five patients (5.2%) had to be excluded from this study because severe chronic pancreatitis made separation of the distal splenic vein from the pancreatic bed difficult. Esophageal transection was performed for these patients. No deaths occurred during the 30 days of treatment. The 5-yr cumulative bleeding rates were 0%, 5.9% and 12.9% in the endoscopic injection sclerotherapy, esophageal transection and distal splenorenal shunt groups, respectively (no statistical significance). In no case in the three groups did death occur because of variceal bleeding. Sixteen patients died, mainly because of underlying liver disease; four were in the endoscopic injection sclerotherapy group, five were in the esophageal transection group and seven were in the distal splenorenal shunt group. No statistically significant difference in survival rate among the three groups was found. These results show that endoscopic injection sclerotherapy is a satisfactory alternative to esophageal transection or distal splenorenal shunt for the clinical management of patients with esophageal varices.
We report here the results of endoscopic injection sclerotherapy performed in 1,000 consecutively treated Japanese patients with esophageal varices. This prospective study covered the period from 1982 to 1990. Variceal bleeding was controlled in 215 (97.7%) of 220 patients. Esophageal varices were completely eradicated in 778 patients (77.8%); the mean number of sessions was 4.2. In only 3 of the 778 patients did esophageal varices of the same size recur. Small, dilated, venous vessels that required additional sclerotherapy in follow-up endoscopy at 3-mo intervals appeared in 171 (22.2%) of 778 patients. The cumulative nonbleeding rate at 5 yr was 94.5% in patients in whom the varices had been eradicated. Deaths caused by upper gastrointestinal bleeding accounted for 2.6% of cases, whereas the rates of liver failure and hepatoma were 4.6% and 47.3%, respectively. The 5-yr cumulative survival rate was 54.1% in patients without concomitant hepatoma; it was 12.0% in patients with hepatomas. Multivariate analysis showed that hepatoma, Child classification, indication (acute, elective or prophylactic) and eradication were independent factors that significantly influenced survival time. This study clearly shows that close follow-up with endoscopy and complete eradication lead to significant reduction in bleeding from esophageal varices and reduction of mortality related to this bleeding.
In Japan, non-shunting procedures and selective shunt such as esophageal transection (ET), and distal splenorenal shunt (DSRS) have been widely performed. A prospective randomized trial was done to assess the effects of EIS and DSRS for treating patients with esophageal varices. Ninety-six Japanese with good liver function (Child A or B) and large esophageal varices were randomly assigned to one of three groups given different treatments; (EIS, n = 32), (ET, n = 32) and (DSRS, n = 32). Five patients (15.6%) of the DSRS group has to be excluded from this study, because of severe chronic pancreatitis. No patient died within 30 days of the treatments. The 5-year cumulative bleeding rates were 0%, 4.3% and 12.1% in the EIS, ET and DSRS groups, respectively, with no statistical significances. In no case in the three groups did the death occur because of variceal bleeding. Nineteen patients died mainly due to the underlying liver disease; 5 in the EIS, 5 in the ET and 9 in the DSRS group. There was no statistically significant difference in the survival rates among the three groups. We conclude that EIS is a satisfactory alternative to ET or DSRS for the management of patients with large esophageal varices.
Several viologen-tagged oligodeoxynucleotides in the form of covalent linkage at the specific site of the phosphorous backbone were synthesized and characterized. Incorporation of viologen molecules was confirmed by the 31P-NMR, 20% PAGE analysis, enzymatic degradation, and uv, ESR spectra of the derived cation radical. The Tm values and CD spectra of the modified strands with their complementary strands indicate that the introduction of the viologen molecule via linker arm causes no significant perturbation in duplex structure.
Fifty cirrhotic Japanese patients with oesophageal varices underwent sclerotherapy in a prospective randomized trial carried out to examine the effects of human thrombin given concomitantly with the sclerosant 5 per cent ethanolamine oleate. The two groups (25 patients each) were comparable with regard to size of the oesophageal varices, and the aetiology and severity of the liver disease. Twenty-five patients, 13 and 12 in the thrombin + and - groups, respectively, had at least one episode of variceal bleeding. The remaining 25 were given prophylactic injections. There was a significantly lower rate of occurrence of bleeding from injection sites when the injection needle was removed at the initial session of sclerotherapy in the thrombin + group, where human thrombin was injected (0.2-0.3 ml, 100-150 units per injection) just before removal of the injection needle. Endoscopy at 1 week after the initial session showed a significantly (P less than 0.05) higher rate of disappearance of red colour signs on varices in the thrombin + group (96 per cent) than in the thrombin - group (72 per cent). Fibrin degradation product E-fraction (FDP-E) values increased 1 h, 1 day and 6 days after the initial session of sclerotherapy in the two groups. The rate of increase in FDP-E values 1 h after sclerotherapy was significantly larger (P less than 0.001) in the thrombin + than in the thrombin - group. There was no clinical sign of disseminated intravascular coagulation. Administration of human thrombin plus a sclerosant seems to be useful and efficacious, especially for patients with huge oesophageal varices.
Thirty patients with esophageal varices, portal venous obstruction and a histologically proven normal liver underwent either one of 2 different types of surgery. Shunt surgery was performed on 20 patients: 9 had a mesocaval shunt, 3, a splenorenal shunt, 4, a left gastric venacaval shunt, and 4, a distal splenorenal shunt. Conversely, direct interruption was performed on the other 10 patients; 6 underwent an esophageal transection, and 4 underwent a resection of the proximal stomach. Re-hemorrhage occurred in 7 of the former 20 patients but not in any of the 10 on whom the direct interruption method was used. In 6 of these 7 patients who experienced rebleeding, subsequent direct interruption surgery led to control of the bleeding. One patient died of a variceal hemorrhage one month postoperatively. The total 10 year cumulative survival rate was 86.3 per cent. In the light of these findings, we believe that methods of direct interruption, such as esophageal transection, may well be the approach of choice for patients with esophageal varices caused by extrahepatic portal venous obstruction.
We examined the pulmonary hemodynamics and morphology after injection of a sclerosing solution of 5% ethanolamine oleate (EO) into 24 normal dogs. EO of 0.5 ml/kg (n = 5), 1.0 ml/kg (n = 6), and 3.0 ml/kg (n = 7) was injected through the jugular vein into the right atrium for pathological examination and gravimetric study of the lung, while monitoring the pulmonary hemodynamics for 12 h. Normal saline of 3.0 ml/kg was injected into the remaining 6 control dogs, using the same method. Cardiac output significantly decreased immediately after injection of the sclerosant in all dogs given 0.5 ml/kg, 1.0 ml/kg and 3.0 ml/kg injections of EO; however, there was a tendency toward recovery from 6 h after injection in dogs given 0.5 ml/kg and from 9 h in dogs given 1.0 ml/kg. Pulmonary hypertension just after injection and hypoxia at 9-12 h occurred only when 3.0 ml/kg was injected. Irreversible pulmonary hemorrhage was present in the excised lungs in 4 of 7 dogs given 3.0 ml/kg, while there were no significant lesions in the other dogs. The lung water content in cases of 1.0 and 3.0 ml/kg injections was significantly higher than that in the controls, while there was no significant difference between those given 0.5 ml/kg and of the controls. The findings obtained in this study suggest that EO less than 0.5 ml/kg used for sclerosing esophageal varices seems to have little untoward influence on pulmonary hemodynamics and morphology.
Intra-operative and postoperative endoscopy were used in 16 patients with portal hypertension to investigate whether intra-operative elimination of oesophageal varices by oesophageal transection with devascularization leads to prevention of variceal recurrence and rebleeding. Intra-operative elimination of the varices was achieved in 12 patients. In ten patients the varices recurred and in two cases rebled, during the follow-up period of 6-43 months (average 25 months). Of the ten patients with recurrent varices, eight (including the two who bled acutely in the postoperative period) successfully underwent endoscopic injection sclerotherapy. Postoperative endoscopy was performed at 5-monthly intervals. It is concluded that intra-operative elimination of the varices will not prevent recurrence and that a closer follow-up using endoscopy more than three times a year is a significant aid in the management of these patients.
Forty-five cirrhotic patients with oesophageal varices underwent endoscopic injection sclerotherapy in a prospective randomized trial carried out to compare two sclerosing agents (5 per cent ethanolamine oleate and 2 per cent sodium tetradecyl sulphate (STD] with respect to safety, efficacy and complications. Twenty-three patients were allocated to the ethanolamine group and twenty-two to the STD group. The rate of control of acute bleeding was 100 per cent (6/6) in the ethanolamine group and 75 per cent (3/4) in the STD group. There was a significantly lower rate of postinjection bleeding after the over-tube was removed at the initial session of sclerotherapy when ethanolamine was injected 0/23 versus 7/22, 32 per cent; P less than 0.01) and at the second session there was a significantly (P less than 0.01) higher rate of jet-like bleeding from injection sites in the STD group (6/21, 29 per cent) than in the ethanolamine group (0/22). The disappearance rate of red colour signs 1 week after the initial session of sclerotherapy in the ethanolamine group was 100 per cent and 62 per cent in the STD group. Early oesophageal ulcers developed less frequently in the ethanolamine group (0 and 9 per cent) than in the STD group (24 per cent and 43 per cent both after the initial (P less than 0.05) and the second session of sclerotherapy (P less than 0.01]. Early bleeding from an oesophageal ulcer occurred only in the STD group (5/21, 24 per cent) before the third session of sclerotherapy (P less than 0.05). The rate of early mortality did not differ between the two groups. We conclude that ethanolamine seems to be safer and more efficacious than STD for sclerosing oesophageal varices.
Hypersplenism was not relieved by distal splenorenal shunting in 46 of 47 Japanese patients with nonalcoholic cirrhosis of the liver. However, the platelet count significantly increased by 40 percent of the preoperative value, whereas the increment in the white blood cell count was nil. Though the platelet count in 47 patients with a patent shunt did not significantly differ from that in another 7 patients with an occluded shunt, the rate of increase was significantly higher in those with patency than in those with early occlusion throughout the postoperative period and in those with late occlusion 6 months after operation. The increased rate of the platelet count can thus serve to screen patients for shunt patency.
The safety efficacy and complications of injections of large and small volumes of 5% ethanolamine oleate (EO) were examined prospectively in the sclerotherapy of esophageal varices in 39 consecutive cirrhotic patients. Twenty patients were randomly allocated to the large-volume group (LVG) injected with up to 30 ml per session, and 19 to the small-volume group (SVG) injected with up to 15 ml per session. The two groups were comparable with regard to age, etiology and severity of liver disease. Post-injection bleeding occurred in 15.8% (3/19) after 1-3 sessions in the SVG and in 0% in the LVG. The LVG showed a significantly higher rate of decrease in variceal size (95.0% vs 53.2%, p less than 0.05) and disappearance of red color signs (RCS) on the variceal surface (95.0% vs 52.6%, p less than 0.01) one week after the initial session. The treatment period and number of sessions of endoscopic injection sclerotherapy (EIS) for eradication of varices were significantly (p less than 0.01) smaller in LVG than in SVG (LVG: 2.7 +/- 0.6 sessions over 4.2 +/- 0.7 weeks vs SVG: 5.4 +/- 0.9 sessions over 6.0 +/- 1.6 weeks). There were no life-threatening complications, and the incidence of minor complications did not differ between the two groups. The persistence of RCS and the occurrence of post-injection bleeding may imply that esophageal varices are not always completely obliterated despite 1-3 sessions in the SVG. We conclude that the large volume of EO is superior to the small volume for repeated EIS to eradicate esophageal varices.