Deficiency of endogenous prostanoids in gastric and duodenal ulcer diseases

The levels of prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (PGF₁α) and thromboxane B₂ (TXB₂) in endoscopic biopsy specimens from the gastric and duodenal mucosa of healthy volunteers and ulcer patients were measured by radio-immunoassay. The PGE₂ and PGF₁α levels in the mucosa of the corpus of the stomach were lower and the TXB₂ level was higher in 10 patients with gastric ulcer in the corpus than in the 16 healthy subjects. The PGE₂ level in the antral mucosa of 14 patients with gastric ulcer in the antrum was lower than in the controls. In 18 patients with duodenal ulcer, PGE₂ deficiency was more widespread in the entire gastric and duodenal mucosa while the reduced PGF₁α level was limited in the gastric corpus. Lower levels of PGE₂ in patients with antral or duodenal ulcer and of PGE₂ and PGF₁α in patients with corpus ulcer in the anatomical mucosal area including the ulcer site may predispose the mucosa to ulceration.     

Class IC Antiarrhythmic Drugs, Flecainide and Pilsicainide, Produce ST Segment Elevation Simulating Inferior Myocardial Ischemia

ST Elevation with Flecainide and Pilsicainide . Flecainide and pilsicainide, Class IC antiarrhythmic drugs with slow kinetics, were administered to a 64-year-old man experiencing ventricular tachycardia. Both drugs suppressed the arrhythmia, but caused ST segment elevation in leads II, III, and aVF. No evidence of ischemic heart disease was detected. Withdrawal of the drugs eliminated the ST change. Because these drugs frequently are used to treat tachyarrhythmias in patients who may present with chest pain, this rare ECG manifestation of Class IC drugs should he recognized to avoid misdiagnosis of acute interior myocardial infarction.     

Reliability and validity of the Japanese version of the Yale-Brown Obsessive-Compulsive Scale

Abstract The reliability and validity of the Japanese version of the Yale-Brown Obsessive-Compulsive Scale (JY-BOCS) were determined by 20 raters for 12 Japanese patients with obsessive compulsive disorder at four institutions. Interrater reliability for the total JY-BOCS score was excellent, and the intraclass correlation coefficient was high (ICC = 0.960). Internal consistency was also excellent (Cronbach's α= 0.889). Concurrent and discriminant validity of the JY-BOCS was examined by comparing the scores on the JY-BOCS with those on the Maudsley Obsessional Compulsive Inventory (MOCI) and scales for depression and anxiety. A slight correlation was found between scores on the JY-BOCS and MOCI, but no significant correlations were found between scores on the JY-BOCS and those on scales for depression or anxiety.     

The Acute and Chronic Toxicities of Nivalenol in Mice

The Acute and Chronic Toxicities of Nivalenol in Mice. Ryu,J.-C, Ohtsubo, K., Izumiy-ama, N., Nakamura, JL, Tanaka, T.,Yamamura, H., and Ueno, Y. (1988). Fundam. Appl Toxicol. 11,38–47. In an attempt to ascertain precisely the toxiceffects of nivalenol (N1V), we conducted the determination ofLD50 values, and interim kills during the carcinogenic studyin mice. LD50 values (mg/kg) of NIV in 6-week-old male ddY micewere determined as 38.9 (po), 7.4 (ip), 7.2 (sc), and 7.3 (iv).Seven-week-old female C57BL/6CrSlc SPF mice were fed diets containing0, 6, 12, and 30 ppm (mg/kg) NIV over 1 year, and were assessedfor effects on body weight gain, feed efficiency, terminai organweights, hematology, and histopathology. The rates of body weightgain and feed efficiency showed a good dose-dependent correlationin all experimental periods. Gross and histopathological evaluationof the liver, thymus, spleen, kidneys, stomach, adrenal glands,pituitary gland, ovaries, sternum, bone marrow, lymph node,brain, and small intestines with or without Peyer's patch portionfrom control and all NIV-exposed mice revealed that these tissueswere normal in appearance and in histopathological structure.Also, no changes were observed in the ultrastructural studieson the bone marrow. Dietary NIV did, however, cause dose-dependentdecreases of absolute organ weights (mg) and increases of relativeorgan weights (mg/g body weight) in the terminal organ weightsrecorded. A significant leukopenia was observed in the 30 ppmgroup at 6 months and in all NIV-treated groups at 1 year. Nomarked changes were observed in the other hematological parameters.These results indicated that 6 ppm or more of dietary NIV for1 year showed a characteristic toxic effect of trichothecenemycotoxins in mice.     

A Case of Biliary Cystadenocarcinoma Followed up for Five Years

We report on a case of an 80-year-old male with autopsy-confirmed biliary cystadenocarcinoma. The tumor's growth was followed up for five years. CT findings on first admission revealed that the cyst walls of the tumor were smooth. However, a CT taken four years later showed large cysts with irregular walls which were growing invasively and expanding beyond the liver. The patient died of liver dysfunction caused by obstructive jaundice due to the liver tumor, and an autopsy was performed. Histologic examination of the autopsy material revealed a multilocular tumor that was identified as being a biliary cystadenocarcinoma and microscopic lung metastases were seen. The character of the multilocular cyst with septations covered by papillary proliferation of atypical columnar epithelium and many remaining portions with low grade dysplasia led us to suspect the tumor was derived from a cystadenoma.     

Inhibition of Nifedipine Metabolism in Dogs by Erythromycin: Difference between the Gut Wall and the Liver

The purpose of this study was to evaluate possible interaction of nifedipine with erythromycin or rokitamycin in the intestinal mucosa. Male beagle dogs were orally administered nifedipine (10 mg), with or without oral pre-medication with erythromycin (300 mg), and 300 mg erythromycin or rokitamycin twice a day for 3 days. The experiments were of randomized cross-over design with a two-week wash-out period between dosing regimens. Erythromycin pre-medication for 3 days resulted in a significant increase in the area under the serum nifedipine concentration-time curve (AUC), whereas the curve for one nifedipine metabolite (M-2) decreased significantly. When the effects of erythromycin on the metabolism of nifedipine were studied using dog liver microsomes it was found that erythromycin significantly inhibited formation of M-2 but not of the metabolite M-1. These results indicate that formation of M-2 from M-1 in the liver might be reduced by erythromycin premedication. To avoid possible metabolism in the gut, the dogs were then administered 8 mg nifedipine into the peritoneal cavity, with or without multiple dose pre-treatment with erythromycin for 3 days. After intraperitoneal administration of nifedipine, the maximum concentration (C_max) of nifedipine increased significantly. After pre-administration of erythromycin the relative bioavailability of nifedipine after oral administration was increased compared with injection into the peritoneal cavity. In-vitro study using rat intestinal microsomes and the in-vivo rat intestinal loop technique also showed that pre-administration of erythromycin inhibits nifedipine metabolism in the small intestine.     

FK506 promotes liver regeneration by suppressing natural killer cell activity

We examined the mechanism of promotion of liver regeneration by tacrolimus hydrate (FK506), a potent immunosuppressant, after partial hepatectomy. The administration of FK506 significantly increased the bromodeoxyuridine (BrdU) labelling index at 36 and 48 h after 70% hepatectomy compared with the placebo group. Using the same model, we examined the effect of FK506 on the expression of hepatocyte growth factor (HGF) and transforming growth factor-β1 (TGF-β1) and found no changes in HGF and TGF-β1 mRNA expression in the liver or in the HGF protein concentration in plasma. We found that pretreatment with FK506 markedly reduced the activity and number of liver-resident natural killer (NK) cells at the time of partial hepatectomy. Our observations suggest that the promotion of liver regeneration by FK506 may be attributable to a reduction in the number of liver-resident NK cells and to inhibition of their activity.     

Evaluation of Endoscopic Resection of Gastric Tumors Following Local Injections of HSE (Hypertonic Saline-Epinephrine Solution)

Abstract: The Endoscopic resection of gastric tumors following local injections of hypertonic saline-epinephrine solution (ERHSE) was performed on 72 lesions (69 patients) of gastric tumors at Yoyogi Hospital etc. from March, 1983, to December, 1989. These included 40 cases of adenoma, 31 cases of carcinoma, and one carcinoid tumor. The average length of the major axis of the endoscopically resected tumors was 12 ± 9 mm. The curative rate at the first attempt was 94% (64 of 68 lesions). The curative rate of the final procedure was 99% (67 of 68 lesions). This excluded 4 lesions in 3 patients in whom a follow-up examination was not possible. There was no relationship found between the final cure rate and the form and location of the lesions. Fifty four lesions were resected with one session of snare cautery; the average length of their major axis was 9 ± 6mm. The resection of 18 lesions was done piecemeal, and the average length of their major axis was 20 ± 10mm. A statistical significance was noted between the size of the lesions which could be resected with one session of snare cautery and those treated by the piecemeal method, but no difference was noted in the location of lesions for the two groups. The indication for ERHSE was assessed in accordance with the cases that resulted in piecemeal resection, those in which the first ERHSE left residual tumor tissues, and those with perforation. ERHSE could be performed with difficulty on lesions which were (1) on the sharply bending gasric wall, (2) observed only tangentially, (3) inadequately observed. These lesions were situated on the gastric fornix, cardia, and their vicinities, the gastric angulus, posterior wall and greater curvature of the gastric body, and anterior wall and lesser curvature of the middle to the upper gastric body.