Objective Quantification of Grade of Atypia in Epithelial Tumors of the Stomach by Image Processing

An image processing technique to extract tubular and nuclear areas from histological specimens stained with hematoxylin was established. Two indices representing tubular density and nucleus-to-cytoplasm ratio of glands were examined in intestinal-type tumor of the stomach. In specimens clearly stained with hematoxylin, significant differences of brightness among nuclei, cytoplasm and stroma can be obtained. Image processing by computer enabled us to identify nuclei, cytoplasm and stroma by utilizing the differences of brightness among them. Both indices tended to increase with severity of histological atypia and their values in the tubular adenoma group were significantly different from those in the tubular adenocarcinoma group (P< 0.05). Therefore, these two indices could be regarded as valid and objective measures of the grade of histological atypia. Eighty-four percent of tubular adenoma and tubular adenocarcinoma cases were classified correctly with the discriminant formula and critical value calculated from the two indices on the basis of measurement of the images magnified by 40 times. There is, however, still a non-negligible overlap of discriminant scores between the tubular adenoma group and tubular adenocarcinoma group. More indices representing histological atypia will be required to allow objective differential diagnosis between malignant and benign lesions.     

Inhibition of cell growth and macromolecule biosynthesis of human promyelocytic leukemic cells by acridone alkaloids

Acridone alkaloids of plants indigenous to the Orient were isolated and purified, and their chemical structures were determined. A total of 50 acridones and their synthetic derivatives were subjected to rapid screening for inhibition of macromolecular synthesis using radiolabeled precursors of DNA, RNA and protein. These compounds were then studied to examine cell growth inhibition of human promyelocytic leukemic cells (HL-60). Cytotoxicity was studied using the trypan blue exclusion method. Of 50 compounds evaluated for cell growth inhibition, 12 compounds showed IC₅₀<10 μM; 12 compounds, 10-20 μM; 8 compounds, 20-100 μM; and 18 compounds, >100 μM.     

Myoclonic Astatic Epilepsy Presenting Eyelid Myoclonic Seizures Induced by Closing of Eyes

Abstract: A male infant with myoclonic astatic epilepsy showed myoclonic seizures of the eyelids by closing of the eyes. There was no photosensitivity in EEG with flash-stimulation and he could induce seizures even in total darkness. The latency between a lid closure and onset of seizure discharges on EEG was relatively long (0.3-0.5 second). Epileptic seizures in this patient may be induced via a brainstem reticular formation, and elevated Bell's position seems to be the necessary stimulus to produce seizures.     

Breast masses with mixed cystic-solid sonographic appearance

Retrospective analysis was performed for 56 breast masses with mixed cystic and solid sonographic patterns encountered in the last 5 years at Keio University Hospital, with the objective of elucidating their significance. The lesions were classified into two major groups: tumor with cyst (TWC—solid mass with cystic component) and intracystic tumor (ICT—cystic mass with solid component). According to the pathological diagnosis, 57% were benign and 43% were malignant. Fifty eight percent of malignant lesions were shown to have a TWC pattern and 42% an ICT pattern. Among benign lesions, 66% were shown to be TWC and 34% ICT. In malignant tumors, 96% of the cases showed irregular shape and heterogeneous internal content. Even in benign lesions, a high incidence of irregular shape and rough border was found, although the predominant internal echo texture was homogeneous, and threedimensional (3-D) contour was not clear. In conclusion, we observed that in the TWC group, the lack of a defined 3-D contour is the most important criterion, and tumors with multiples cysts tend to be benign. © 1993 John Wiley & Sons, Inc.     

Altered pharmacokinetics and excessive hypotensive effect of candesartan in a patient with the CYP2C91/3 genotype

An 89-year-old man with severe hypertension (190/82 mm Hg) and chronic heart failure (New York Heart Association class II) despite treatment with benidipine, doxazosin mesylate (INN, doxazosin), and furosemide was given oral candesartan cilexetil (4 mg/d), an angiotensin II type 1 receptor blocker metabolized via cytochrome p450 (CYP) 2C9. Two days later, he started to have severe dizziness and returned to the hospital on the fourth day without taking any of his medications. The blood pressure 30 hours after the last dose of candesartan was 126/64 mm Hg. Polymorphism analysis revealed the heterozygous poor metabolizer genotype CYP2C9*1/*3. The area under the concentration-time curve and the mean residence time of candesartan were both increased 2.5-fold, and the oral clearance of candesartan was 48% lower than that of the average elderly Japanese patient with hypertension. These results suggest that the CYP2C9*1/*3 genotype could be associated with decreased clearance and increased plasma concentration of candesartan, potentially enhancing its hypotensive effect.     

Biliary endoprosthesis in bile duct obstruction secondary to hepatocellular carcinoma

The effect of biliary endoprosthesis was evaluated in 13 patients with major bile duct obstruction secondary to invasion by hepatocellular carcinoma. In 12 patients major portal vein branches were also invaded by the tumors. After several days' instillation of nasobiliary or percutaneous drainage tubes to flush the bile ducts, biliary endoprosthesis was performed either endoscopically (N=9) or percutaneously (N=4). Significant decrease (less than 50% of initial values) of alkaline phosphatase and bilirubin levels was observed in eight and two patients on day 20, respectively. Twelve patients died of hepatic failure at 27–132 days (mean 60 days). One patient without portal vein involvement is currently alive at 300 days. Biliary endoprosthesis has a limited role in the palliation of bile duct obstruction secondary to hepatocellular carcinoma, and the prognosis may be influenced mainly by the underlying hepatic function.     

Successful laparoscopic distal pancreatectomy for a large solid pseudopapillary neoplasm: A case report

A 30‐year‐old Japanese woman presented at our hospital with a pancreatic tumor. Contrast‐enhanced CT revealed a tumor with a 12‐cm diameter in the pancreatic body and tail. In the preoperative setting, endoscopic ultrasound‐guided fine‐needle aspiration permitted a histopathological diagnosis of solid pseudopapillary neoplasm. Twhe patient underwent laparoscopic distal pancreatectomy with splenectomy. Our procedure involved three steps. Firstly, the splenic artery was occluded to block inflow of blood to the tumor. Then, we transected the neck of the pancreas using radical antegrade modular pancreatosplenectomy. Finally, hand‐assisted laparoscopic surgery allowed us to secure the operating field and easily handle the large tumor. This enabled us to accomplish laparoscopic distal pancreatectomy, and en‐bloc resection was completed. The patient was discharged without major complications. Laparoscopic distal pancreatectomy for huge solid pancreatic tumors can be completed safely.     

Inhibition of the subgenomic hepatitis C virus replicon in huh-7 cells by 2'-deoxy-2'-fluorocytidine

2'-Deoxy-2'-fluorocytidine (FdC) is a potent inhibitor of the hepatitis C virus RNA replicon in culture, and FdC-5'-triphosphate is an effective inhibitor of the NS5B polymerase. Dynamic profiling of cell growth in an antiviral assay showed that FdC caused cytostasis due to an S-phase arrest. These observations demonstrate that FdC treatment is affecting both a viral target and a cellular target.     

Effects of intravenous ethanol on hepatic and pancreatic blood flow in dogs

Changes in hepatic and pancreatic blood flow in response to ethanol infusion were determined simultaneously and continuously in anesthetized dogs, using a transit-time ultrasonic flowmeter and a laser-Doppler flowmeter. In addition, the effect of intravenous ethanol on exocrine pancreatic secretion was investigated. With a background infusion of secretin, ethanol (1.3 g/kg body wt) was infused intravenously over a 40-min period. Ethanol infusion significantly increased blood flow in the common hepatic artery (by 49%, at the time of the cessation of ethanol infusion), and this increased flow was maintained for 60 min after the cessation of ethanol infusion. In contrast, blood flow in the portal vein was not altered significantly by ethanol. Pancreatic blood flow and secretion showed no significant difference from those seen in the controls. Our data suggest that intravenous ethanol induces a redistribution of the splanchnic blood flow. The increased hepatic arterial flow seen in response to ethanol may play an important role in preventing ethanol-induced hypoxic liver damage.