Effects of insulin-like growth factor-1 on Short bowel syndrome without ileocecal valve in rats.

Insulin-like growth factor-1 (IGF-1) can promote enterocyte proliferation which may be beneficial to postoperative conditions after massive small bowel resection (SBR) including the ileocecal valve (ICV). Wistar rats were subjected to SBR including or preserving ICV and continuously received IGF-1 or saline alone. Nutritional status, enterocyte proliferation, liver damage and hepatic IGF-1 mRNA levels were analyzed. Body weights, serum levels of total protein and transferrin, and enterocyte proliferation were significantly lower after SBR including ICV than preserving it. IGF-1 mRNA levels in the liver were decreased after SBR, especially after SBR including ICV. However, IGF-1 therapy significantly attenuated those decreased levels after SBR including ICV. Furthermore, IGF-1 significantly decreased serum liver transaminase levels which were increased after SBR including ICV. Continuous administration of IGF-1 may be available as a supplemented therapy for short bowel syndrome without ICV.

[Tissue platinum distribution and the effect following intra-arterial injection of cisplatin to metastatic liver cancer--a case report].

A 63-year-old male with advanced esophageal cancer was admitted to our hospital. He received neoadjuvant chemotherapy with intravenous cisplatin and fluorouracil (5-FU), and underwent resection of the esophagus and placement of a gastric tube. Two months later, multiple metastases appeared in the right lobe of the liver. Intermittent arterial infusion chemotherapy with cisplatin and 5-FU were performed. To selectively infuse the drugs into the right hepatic artery, the left hepatic artery was embolized. Treatment had a marked effect in the right lobe, but new lesions were subsequently discovered in the left lobe. The patient died of pleuritis 27 days after the end of cisplatin infusion and 12 months after surgery. In total, 465 mg of cisplatin and 20 mg of nedaplatin were administered. At autopsy, tissue samples were collected to measure the platinum concentration. The result showed the highest value to be in the right lobe, 4.8 times as high as that in the left lobe. It is suggested that the concentration of platinum in tissue is correlated with the anticancer effect of cisplatin to the tissue, despite of the traditional view that the tissue concentration and the effect are not related.

[A case of AFP-producing gastric cancer responding to low-dose CPT-11 and low-dose cisplatin combination chemotherapy].

UNLABELLED: Gastric cancers that produce alpha feto protein (AFP) usually have a poor prognosis. We report an AFP-producing gastric cancer that showed a partial response to low-dose CPT-11 and low-dose cisplatin combination chemotherapy. AFP-producing gastric cancers successfully treated with chemotherapy have been reported, but to our knowledge this is the first report of successful treatment with low-dose CPT-11 and low-dose cisplatin combination chemotherapy. CASE: A 49 year-old woman who had gastric cardiac cancer with esophageal invasion was admitted to our institution. Since AFP-positive cells were demonstrated immunohistochemically in biopsy specimens and levels of AFP in serum were high, AFP-producing cancer was diagnosed. Because of metastasis to Virchow's node and the paraaortic lymph nodes, the tumor was considered unresectable. The patient's poor general condition necessitated chemotherapy with low toxicity and high efficacy. She was treated with low-dose CPT-11 and low-dose cisplatin combination chemotherapy. After two cycles of this treatment, the tumor volume and the serum levels of AFP had decreased markedly. The only side effect of the treatment was leukopenia.

[Diffusion-weighted imaging of brain death: study of apparent diffusion coefficient].

DWI(Diffusion-weighted images) of the brain has been revealed to be useful in diagnosis of several clinical conditions. However, little is known about DWI with regard to brain death. We had opportunities to study patients with brain death. Case 1. A 34-year-old woman experienced cardiopulmonary arrest due to severe ventricular fibrillation, and resuscitated after about 120 minutes. After brain death, DWI showed high signals in the cerebral cortex, putamen, thalamus, brain stem and cerebellum, and ADC(apparent diffusion coefficient) values were 30-40% lower than those of normal volunteers. Case 2. A 45-year-old woman experienced cardiopulmonary arrest due to pontine hemorrhage, and was resuscitated after about 20 minutes. Before brain death, DWI showed high signals in the cerebral cortex, putamen, thalamus, brain stem and cerebellum, and ADC values were the same as those of normal volunteers. After brain death, DWI showed more clearly defined in these areas, but ADC values were 30-40% lower than the first values. DWI and ADC mapping shows areas corresponding to edema of a cytotoxic nature and to ischemic tissue. The characteristic views of high signals in the whole area of the brain were present, and an objective evaluation was possible with DWI after the brain death diagnosis by measuring ADC values.

Specific mutation in exon 11 of c-kit proto-oncogene in a malignant gastrointestinal stromal tumor of the rectum.

Gastrointestinal stromal tumor (GIST) in the distal third of the rectum was detected in a 57-year-old man who underwent an abdominoperineal resection of the rectum. Because the tumor expressed CD34 and c-kit gene product, but did not express smooth muscle actin or S-100 protein, it was diagnosed as an uncommitted type of GIST. Moreover, a specific mutation in the sequence coding the juxtamembrane domain in exon 11 of the c-kit proto-oncogene was revealed by a polymerase chain reaction-single-strand conformation polymorphism method. One year after resection, the patient developed multiple liver metastases. It is suggested that a specific mutation in exon 11 of the c-kit proto-oncogene may have played an essential role in the development of the liver metastases.

Feasibility of a novel weekday-on/weekend-off oral UFT schedule as postoperative adjuvant chemotherapy for colorectal cancer. UFT Compliance Study Group, Kanagawa, Japan.

PURPOSE: When oral anticancer agents are used for adjuvant chemotherapy of colorectal cancer, compliance and feasibility become issues because of the long treatment time. Appropriate studies of these issues are lacking. We investigated compliance and feasibility during a weekday-on/weekend-off schedule of oral UFT (uracil-tegafur) over a period of 1 year administered as adjuvant chemotherapy to patients with colorectal cancer. PATIENTS AND METHODS: A UFT dose of 600 mg/day was prescribed according to a weekday-on/weekend-off schedule to 87 patients after potentially curative resection. Compliance was investigated in three ways: physician interview, patient self-report, and chemical analysis of urine. The results were compared with the dose prescribed. Feasibility was evaluated on the basis of two indices: relative performance (RP), which was the ratio of the actual total dose taken to the total dose planned, and individual dose intensity (IDI), which was the ratio of the actual dose taken to the dose planned during a given period. RESULTS: The compliance assessed by physician interview and by patient self-report conformed well with the prescribed dose, the rate of agreement among the three compliance measures being more than 94%. Chemical analysis of urine in 38 of the patients revealed that they were actually taking the drug. The RP was 0.72, and the IDI was 0.8. CONCLUSION: From these results, the feasibility of the weekday-on/weekend-off schedule was judged to be good. It is suggested that the feasibility would be even better if the dose of UFT was set according to body surface area.

Microwave coagulation therapy for hepatocellular carcinoma.

The efficacy and safety of microwave coagulation therapy (MCT) in patients with hepatocellular carcinoma (HCC) and impaired hepatic reserve were studied. Preoperative background factors, postoperative results, and prognostic factors were compared in 51 patients who underwent hepatic resection (HR group) and 38 patients who underwent microwave coagulation therapy (MCT group). Before surgery, measures of hepatic function, including level of albumin (P = 0.0072), prothrombin time (P<0.0001), hepaplastin test (P = 0.0088), and the radioactivity of technetium-99m galactosyl-human serum albumin 15 min in the liver after injection divided by that in both liver and heart (P <0.0001) were significantly lower in the MCT group than in the HR group. The indocyanine green dye retention rate at 15 min was significantly greater (P<0.0001) in the MCT group than in the HR group, and a significant difference was noted in Child-Pugh grade between the groups (P<0.0001). Operative time (P = 0.0014) and blood loss during surgery (P = 0.0005) were significantly lower in the MCT group than in the HR group. In contrast, no significant differences were recognized between the groups in the changes in postoperative liver function, or in the rates of morbidity, mortality, local recurrence, and survival. Moreover, the type of treatment (HR or MCT) was not a prognostic factor. The results indicate that MCT can be used safely as an alternative to hepatic resection in patients with poor liver function without reducing the efficacy of local control.

[Neuromonitoring of acute internal carotid artery occlusion].

We experienced a patient with acute thrombosis of the unilateral internal carotid artery. We monitored the brain tissue temperature and intracranial pressure not only in both hemispheres simultaneously but also continuously throughout the process of brain death. The patient was a 73-year-old male who presented to our emergency room with right hemiparesis and aphasia. On admission to our department, no specific pathological findings were identified by brain CT. However a following investigation with left carotid arteriogram demonstrated a complete occlusion of the left internal carotid artery. Probes to monitor intraparenchymal temperature (Tip) and intracranial pressure(ICP) were inserted surgically into the bilateral hemispheres, and these two parameters were monitored continuously until the patient's death. Initially, Tip in the infarcted hemisphere was lower than that in the intact hemisphere, and the left hemisphere's ICP was significantly higher than that of the right one. When the ICP in the left hemisphere exceeded 40 mmHg, bilateral ICPs became equal. Brain herniation was confirmed when the ICP became progressively elevated thereafter. Subsequently the bilateral Tips became equal and lower than the bladder temperature following the brain herniation. In this case, we successfully monitored two parameters while the patient was in the process of brain death; i.e., brain ischemia, complete loss of brain circulation and subsequent decrease in the brain tissue temperature.

Specific detection of epstein-barr virus in inflammatory pseudotumor of the spleen in a patient with a high serum level of soluble IL-2 receptor.

A case of inflammatory pseudotumor of the spleen is described in a 63-year-old woman who presented with an intrasplenic tumor and an elevated serum level of soluble interleukin 2 receptor (sIL-2R). Microscopic examination after removal of the spleen revealed that the tumor was composed of mixed cellular infiltrates, mainly lymphocytes and plasma cells, and spindle-cell proliferation. Epstein-Barr virus (EBV) was specifically detected in the tumor by in situ hybridization for EBV RNA. The serum level of sIL-2R level was normalized after splenectomy. EBV infection may play a role in the development of splenic inflammatory pseudotumor and the elevation of sIL-2R level.

Heparin reduces serum levels of endothelin-1 and hepatic ischemia reperfusion injury in rabbits.

Since the role of heparin in hepatic ischemia/reperfusion (I/R) injury is still not fully understood, we investigated the effects of heparin on hepatic I/R injury in rabbits. Heparin was injected into rabbits after inducing partial hepatic ischemia for 1 h. Thereafter, the serum levels of endothelin-1 (ET-1) and liver transaminase, and tissue levels of oxidized and deoxidized hemoglobin (oxHb, deoxHb) in the reperfused liver were analyzed. Microscopic examinations were also performed. The increased serum levels of ET-1 and liver transaminase after reperfusion were significantly reduced by heparin (P > 0.01). Hepatic ischemia reduced oxHb and increased deoxHb. Reperfusion with heparin immediately reduced deoxHb and increased oxHb, and thereafter the balance between the two kinds of Hb also recovered. However, reperfusion without heparin did not demonstrate any similar recovery, but instead gradually exacerbated the dissociation. Microscopically, heparin appeared to normalize I/R-induced activation of hepatic stellate cells which are the target cells for ET-1. These results suggest that heparin improves the hepatic I/R injury caused by sinusoidal microscirculatory disturbances partly via an inhibition of the ET-1 increase.

Susceptibility to lipopolysaccharide of cholestatic rat liver produced with bile duct ligation: assessments of the mitochondrial glutathione pool and the effects of N-acetylcysteine.

We investigated whether rats with obstructive jaundice produced with bile duct ligation for 2 weeks are more susceptible to the additional stress of lipopolysaccharide (LPS) administration than sham-operated rats and also examined the effects of N-acetylcysteine (NAC) on LPS stimulation in rats with bile duct ligation. The effects of LPS on the mitochondrial glutathione pool and on oxidative stress of polymorphonuclear leukocytes were investigated in cholestatic rats. Serum concentrations of alpha-glutathione S-transferase showed that lipopolysaccharide stimulation caused more severe hepatocellular injury in cholestatic rats than in sham-operated rats. In addition, concentrations of mitochondrial reduced and oxidized glutathione and hepatic adenosine triphosphate showed that LPS stimulation decreased mitochondrial function more in cholestatic rats than in sham-operated rats. Intraperitoneal administration of NAC for 2 weeks significantly improved mitochondrial function and decreased hepatocellular injury. However, the oxidative stress of polymorphonuclear leukocytes that had infiltrated hepatic tissue was increased by NAC. The present results indicate that the cholestatic liver is susceptible to the additional stress of LPS, that NAC suppresses the adverse effects of LPS in cholestatic livers, and that the oxidative stress of polymorphonuclear leukocytes is not significantly involved in mitochondrial dysfunction or hepatocellular injury in this model.

Intravenous detergent poisoning.

CASE REPORT: In the literature regarding surfactant poisoning, the route of exposure has almost always been oral. We report a case in which about 40 mL of bath detergent for home use was self-injected. The primary pathophysiologic effects were relative hypovolemia and cardiac dysfunction. The patient experienced frequent ventricular tachycardia, acute renal failure, rhabdomyolysis, hemolysis, and coagulation dysfunction. Intensive care included the administration of antiarrythmial agents and hemodialysis. The patient survived and was discharged from our hospital without sequelae.

Adenovirus-mediated insulin gene transfer improves nutritional and post-hepatectomized conditions in diabetic rats.

BACKGROUND: Impaired nutritional conditions in patients with diabetes are significant risk factors after major abdominal surgery. We constructed recombinant adenovirus vector carrying the human insulin gene (AxCAIns) for in vivo insulin gene transfer to improve metabolic impairments after a major operation in patients with diabetes. We tested the effects of AxCAIns on nutritional and post-hepatectomized conditions in rats with diabetes treated with streptozotocin (STZ). METHODS: AxCAIns was injected into the spleen in diabetic rats treated with STZ. Blood levels of glucose, total protein, albumin, and C-peptide of human proinsulin were measured and the expression of transferred human insulin gene was analyzed in various organs. Diabetic rats underwent 70% partial hepatectomy with or without AxCAIns injection, and post-hepatectomized conditions were analyzed. RESULTS: STZ-induced hyperglycemia was reduced by AxCAIns injection. Decreased serum levels of total protein and albumin in diabetic rats were significantly restored to normal levels by AxCAIns injection, and human C-peptide was detected in the sera of AxCAIns-treated rats. Human preproinsulin messenger RNA, which represented the expression of transferred insulin gene, was detected in the liver and the spleen, but not in other organs. Serum albumin levels, remnant liver weight, and ratios of postoperative body weight to preoperative body weight were significantly increased by AxCAIns in hepatectomized diabetic rats. CONCLUSIONS: AxCAIns injection to the spleen efficiently transferred the human insulin gene mainly into the hepatocytes and produced enough human proinsulin to improve nutritional impairments and post-hepatectomized conditions in diabetic rats. Insulin gene transfer with intrasplenic injection of AxCAIns may be available to improve metabolic impairment after major abdominal surgery in patients with diabetes.

Oxidative homocoupling of chiral 3-arylpropanoic acid derivatives. Application To asymmetric synthesis of lignans

The oxidative homocouplings of lithium enolates of (4S)-3-(3-arylpropanoyl)-4-isopropyl-2-oxazolidinones and (4R, 5S)-1-(3-arylpropanoyl)-3,4-dimethyl-5-phenyl-2-imidazolidinones gave the corresponding R,R-dimers stereoselectively with TiCl(4), PhI(OAc)(2), or CuCl(2) as an oxidant. The stereoselectivity can be explained by a radical coupling mechanism. Optically active dibenzylbutyrolactone lignans, such as (-)-hinokinin and (-)-dimethylmatairesinol, and dibenzylbutanediol lignans, such as (-)-dihydrocubebin and (-)-dimethylsecoisolariciresinol, were synthesized from the major R,R-dimers. The oxidative coupling of (4R, 5S)-1-(3-arylpropanoyl)-3,4-dimethyl-5-phenyl-2-imidazolidinones with LDA-I(2) gave R,S-dimers mainly, and this result can be explained by an S(N)2 mechanism.

Liver function assessed by increased rate of portal venous blood flow after oral intake of glucose.

OBJECTIVE: To find out whether an increased rate of portal venous blood flow after oral intake of glucose could be used to estimate liver function. DESIGN: Prospective study. SETTING: University hospital, Japan. SUBJECTS: Sixty patients, of whom 23 had hepatocellular carcinoma and liver cirrhosis, 21 had tumours metastatic to normal liver, and 16 had obstructive jaundice treated with percutaneous transhepatic biliary drainage (PTBD). INTERVENTION: Portal flow was measured after oral intake of glucose 75 g using pulsed-Doppler ultrasonography. RESULTS: The ratio of portal flow 30 minutes after glucose intake to that before intake (PVFR30) was significantly lower in cirrhotic patients than in those with metastases and a normal liver. A PVFR30 of less than 1.5 indicated impaired hepatic function assessed by the Child-Pugh scores, indocyanine green clearance test, prothrombin time, and hepaplastin test. It also indicated less reduction in total bilirubin concentrations in the first week after PTBD. CONCLUSIONS: Results suggest that PVFR30 can be used to estimate liver function and predict outcome after PTBD.

Improvement of portal flow and hepatic microcirculatory tissue flow with N-acetylcysteine in dogs with obstructive jaundice produced by bile duct ligation.

OBJECTIVE: To find out if N-acetylcysteine (NAC) would improve hepatic circulation in dogs with obstructive jaundice. DESIGN: Open laboratory study. SETTING: University hospitals, Japan and France. MATERIALS: 14 male beagle dogs and 10 male Wistar rats. INTERVENTIONS: Obstructive jaundice was produced by ligation of the common bile duct (CBD) for 7 days in both dogs and rats. Either 5% dextrose (control group, n = 7) or NAC (NAC group, n = 7) was given to dogs. Sinusoidal endothelial cells were obtained from rats after ligation by elutriation, and varying amounts of NAC were given. MAIN OUTCOME MEASURES: The volumes of portal blood flow and hepatic microcirculatory tissue flow were reduced after ligation of the CBD, but those increased after NAC had been given to dogs with obstructive jaundice. NAC increased the concentrations of plasma cyclic 3',5'-guanosine monophosphate (cGMP). It also increased concentrations of serum and hepatic-reduced glutathione, and hepatic adenosine triphosphate (ATP) in cholestatic dogs, and secretion of cGMP from sinusoidal endothelial cells from rats with obstructive jaundice. CONCLUSION: These results suggest that NAC given intravenously effectively improves hepatic circulation and hepatic function in dogs with obstructive jaundice.