Clinical efficacy of sucralfate in the treatment of gastric ulcer.

We performed a randomized, single-blind study in Japan to investigate the efficacy and safety of two dosage regimens of sucralfate granules, 2 g, twice daily (b.i.d. group, n = 30) and 1 g, 4 times daily (q.i.d. group, n = 27), on ulcer healing in 57 patients with endoscopically proven gastric ulcer. Endoscopy was performed after 4 weeks and, if complete healing was not achieved, again after an additional 4 weeks. Of 57 patients, 11 were excluded from the statistical analysis because of protocol violation (six in b.i.d. group, five in q.i.d. group). Of 46 patients eligible for the analysis of healing rates, four patients in the b.i.d. group (all at 8 weeks) and five patients in the q.i.d. group (two at 4 weeks and three at 8 weeks) were withdrawn due to patients' inconvenience. As the possibility that the withdrawals were due to the treatment failures could not be denied, we used the Kaplan-Meier method and generalized Wilcoxon test/logrank test for the calculation and evaluation of healing rates in this study, respectively. Healing rates at 4 and 8 weeks were 50% and 94% in the b.i.d. group and 35% and 68% in the q.i.d. group. There was no significant difference in healing rates between the groups. No serious adverse effect was observed in either group. These results suggest that the 2 g b.i.d. dose of sucralfate in granule form is at least as effective as the conventional dose of 1 g q.i.d. in the treatment of active gastric ulcers and could lead to better patient compliance.

Two types of aggregate in the cerebral cortex of a seizure-sensitive strain of the Mongolian gerbil.

A 70-kDa protein, P70, found mostly in the pyramidal cells of the cerebral cortex of cobalt-induced epileptogenic rats, has been implicated in epileptogenesis. The presence of a P70-like substance was searched for immunohistochemically in the cerebral cortex of MGS/ldr, a seizure-sensitive strain of the Mongolian gerbil (Meriones unguiculatus) that we previously established. Immunoreactive aggregates were observed in the pyramidal neurons of the motor cortex and the primary somatosensory cortex. Analysis using confocal laser scanning microscopy revealed that the aggregates were often colocalized with a second type of aggregate with red autofluorescence at the marginal zone of the cell somata. Both aggregates appeared and increased before the appearance of generalized tonic-clonic convulsion. These may be involved in some change of physiological function of the cerebral cortex but their presence itself is not enough to determine the occurrence of epileptic seizure because the gerbils that showed no such seizure had both aggregates.

Alcohol consumption and insomnia in a sample of Japanese alcoholics.

The amount of ethanol consumed by chronic alcoholics in a Japanese slum area with persistent insomnia (n = 40) and those without it (n = 40) was compared using a questionnaire. For both groups, the present habitual consumption (PHC) of ethanol per day was most frequently between 60 g and 150 g and no difference was observed between the two groups. In contrast, the maximum habitual consumption (MHC) of ethanol per day throughout the alcoholic history was found to be greater for the insomnia patients than the non-insomniacs (p < 0.001). No difference between the groups was found in the kind of alcoholic drink consumed, with sake (Japanese rice wine) being the most popular in both groups. The results suggest that persistent insomnia in alcoholics is related to excessive alcohol intake and persists even when drinking levels have fallen.

Developmental and seizure-related regional differences in immediate early gene expression and GABAergic abnormalities in the brain of EL mice.

To examine the hypothesized role of the immediate early gene (IEG) response in synaptic plasticity and in epileptogenesis, we studied the spatial specificity of the expression of IEG in EL mice, a well known mutant model of epilepsy. Also to examine the 'GABA hypothesis' in epilepsy, GABA concentration and GAD activity was determined in micro brain regions (10-300 ng) of EL mice related to the focus in the parietal cortex and the hippocampus. We found that the IEG expression after seizures is not related to the seizure pattern, but to the seizure history, seizure threshold and development of EL[s]. Even in the interictal period, EL mice with long seizure histories and very low seizure thresholds demonstrate IEG expression continuously. This is probably strengthened by repeated seizures. The IEG expression site is however located in the hippocampal CA1, which is the final terminal of various inputs from other areas of the limbic system. It is proposed that the continuous expression of IEGs might play a different role from that of transiently expressed IEGs. Developmentally, the site of IEG expression shifted from one site to another in a very similar manner as in the IEG expression with propagation of paroxysmal discharges in each seizure, and the three-dimensional expression area was gradually expanded, suggesting a change in the regional active site during epileptogenesis. These lines of evidence suggest that during development as well as repetitive seizures, frequent expressions of IEGs and syntheses of Fos and Zif proteins might facilitate synaptic conductivity involved in epileptogenesis. The sites of abnormal GABA concentrations and GAD activities were almost the same in the parietal cortex, around Sidman atlas coronal section No. 300 and in the hippocampal CA1 pyramidal cells as the spatio-temporal specific IEG expression sites. These findings strongly suggest that IEG expression and abnormal GABAergic functions are involved in epileptogenesis in EL mice.

Antiepileptic effects of allopurinol on EL mice are associated with changes in SOD isoenzyme activities.

We have investigated the potential antiepileptic action of superoxide dismutase (SOD) activities in the brain of the epileptic mutant EL mouse. EL mice which experienced frequent seizures (EL[s]) had abnormally low levels of SOD isoenzyme activity in the hippocampal area. Once epileptogenicity was established in these animals, activity of cyanide-sensitive Cu,Zn-SOD was maintained at significantly lower levels than in control mice. However, cyanide-insensitive Mn-SOD activity was not different from non-epileptic controls. In EL mice which had not experienced seizure provoking stimulations and exhibited no seizures (EL[ns]) there was moderately lower levels of SOD isoenzyme activities compared to controls. In spite of the low level of Cu,Zn-SOD activity in EL[s] mice, the Cu,Zn-SOD protein content was high in the hippocampus of these animals, suggesting that inactive Cu,Zn-SOD might be induced during development. After allopurinol (ALP) was given orally to EL[s] mice, Cu,Zn-SOD activities increased dramatically in the hippocampus and seizure activity was decreased. Even after 48 h, when antiepileptic action of ALP was lost, the SOD activity was maintained at the high level associated with initial ALP administration. EL[s] mice also showed DNA fragmentation in the hippocampal CA1 region and the parietal cortex, detected with in situ terminal transferase-mediated dUTP nick labeling with the aid of alkaliphosphatase or peroxidase. The degree of DNA fragmentation was less severe in EL[ns] mice. We propose that abnormalities in region specific Cu,Zn-SOD isoenzyme activity might produce free radicals, leading to DNA fragmentations and cell loss. This might contribute to hippocampal epileptogenesis in EL mice.

Eyelid metastasis originated from gastric-cancer.

The incidence of cutaneous metastasis from neoplasms of internal organs is uncommon, and in particular eyelid metastasis from gastric cancer is extremely rare. We report on such a case together with a review of a total of 6 cases. Of the 6 cases, 5 were males and 4 were pathologically low-grade differentiated adenocarcinoma. The presentation of eyelid mass was 3 nodular, 2 diffuse and one ulcerative without characteristics of its location. All the cases involved systemic disease and the effective treatment was not performed. We consider that the number of cases with eyelid metastasis from gastric cancer is actually much higher and that gastroenterologists should pay more attention to such cases in order to adequately grasp the pathogenesis.

Age-related appearance of dystrophic axon terminals in cerebellar and vestibular nuclei of Mongolian gerbils.

In the brains of 360-day-old Mongolian gerbils, numerous swellings immunoreactive to anti-neurofilament antibody were observed in cerebellar and vestibular nuclei. The number of these swellings was the same in two gerbil strains with different susceptibility to spontaneous motor seizures by various stimuli, but much more numerous in gerbils as compared with the 360-day-old Slc:Wistar rats. Such swellings were only occasionally found before 60 days of age in gerbils, but they increased in number about fivefold from 60 to 180 days of age and about quadruple from 180 to 360 days of age. Electron microscopic observation showed that these swellings were dystrophic axon terminals (DATs) whose cytoplasms were occupied with large bundles of neurofilaments, numerous vesicular structures containing membranous and/or granular materials, and many rod-shaped mitochondria. Additionally, other types of DATs displaying degenerative changes of cytoplasmic organelles were observed. ACPase cytochemistry showed that the vesicular structures in the DATs contained ACPase and released it into the cytoplasm.

[Peroral endoscopical diagnosis for the early stage of cancer in bilio-pancreatic system].

PCPS (peroral cholangio-pancreatoscopy), a modality of mother and baby scope systems, was very useful for the diagnoses of bile duct tumors. The endoscopical findings and pathological findings obtained on the biopsy specimen collected under the direct view were valuable. For the diagnosis of pancreatic diseases, PMPS (peroral micro-pancreatoscopy), in which ultrathin quartz fibers are used for the baby scope, was useful. By this method, we could observe the inside of the pancreatic duct through an untreated normal papilla. This is very helpful for endoscopical diagnosis of small pancreatic cancers. EUS (endoscopic ultrasonography) was also a useful method for the diagnosis of small pancreatic cancers. EUS could draw the three layers of the common bile duct and gall bladder walls, and could distinguish a cholesterol polyp from a non-cholesterolic one. Combined application of these methods will aid in the discovery of early stages of cancers in the bilio-pancreatic system.

[Endoscopic treatment of early upper gastrointestinal carcinoma--high-frequency-current polypectomy, laser, and microwave coagulation procedures].

The authors have been treating early gastric carcinoma endoscopically by high-frequency-current polypectomy since 1976, by microwave coagulation since 1982, and by laser coagulation since 1983. In order to achieve absolute curability of early carcinoma, we recommend that polypectomy be performed first, whenever possible. The reason for this is that the resected polypectomised tissue enables a decision to be made as to whether further treatment is necessary, after histopathological examination of the specimen. Otherwise, cases in which snaring is impossible, such as flat or depressed carcinomas of markedly small or large size, should be treated by microwave and/or laser coagulation. In total, we have experienced 92 lesions (83 cases) of early gastric carcinoma treated by all of above 3 methods, and we currently have 5 cases showing more than 5-year survival. Among these, type II a early carcinomas less than 10mm in diameter accounted for the majority; on the other hand, there were 11 type II c cases, also with tumors less than 10mm in diameter. Referring to our surgical data, type II c (without ulcer nor lymph node metastases) less than 5mm in size is limited to the mucosa in 100% of cases, and of 6-10mm in size in 85%. We therefore propose that type II c tumors less than 10mm in size should be treated endoscopically, as well as type II a tumors of the same size. In order to determine the depth of carcinomatous invasion, endoscopic ultrasonography (EUS) is effective. The diagnostic accuracy for Ul(-) early carcinoma is almost 100%, but for Ul(+) cases EUS is not so accurate. Further studies and improvements of EUS are thus needed.

[A report on the epidemiology and the clinical features of the patients with chronic pancreatitis in Hokkaido District].

We carried out through questionnaires the second survey on the epidemiology and the clinical features of chronic pancreatitis in Hokkaido district. Chronic pancreatitis was diagnosed in 258 patients in 19 hospitals during the period April 1977 to December 1984. The ratio of male cases to females was 2.7:1.0 and the average age was 53.9. Alcoholic abuse, observed in 55% of the patients, was a main causative factor. A half of the patients was diagnosed on the basis of pancreatogram and/or image of the pancreas (ultrasonogram and computed tomogram). The incidence of chronic pancreatitis in the second survey was about fourfold over that diagnosed during the period January 1970 to March 1977 in the first survey. Such an increasing number of the patients with chronic pancreatitis in Hokkaido district was considered to be resulted from the difference between two surveys in epidemiological aspects and diagnostic criteria. The proportion of female patients and alcoholic patients was calculated to be increasing. The frequency of the patients diagnosed in a relatively early stage was supposed to be also increasing, because in the second survey a new item (pancreatogram, ultrasonogram and computed tomogram) was added to the diagnostic criteria (histological evidence, pancreatic calcification and definitive disturbance of exocrine pancreatic function) in the first survey. Based on whether alcoholic abuse was causative factor or not, the patients were divided into two groups and the clinical manifestations of both groups were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of multichannel soft tactile sensors having fingerprint structure.

It is possible to accurately recognize the shape of an object or to grip it by setting soft tactile sensors on a robot's hands. We studied a multichannel soft tactile sensor as an artificial hand and evaluated the pressure's response performance from several directions and the slipping and sliding responses. The tactile sensor consisted of multiple pneumatic sensors and a soft cap with a fingerprint structure that was made of silicone gum and was separated from multiple spaces. Evaluation tests showed that the multiple soft tactile sensors estimate both an object's contact force and its contact location. Our tactile sensor also measured the object's roughness by the slide on surface texture.

Robot hand with soft tactile sensors and underactuated control.

We developed a robot hand with three fingers and controlled them using underactuated control to obtain a more flexible grip. With underactuated control, we can flexibly operate an artificial robot hand and reduce the number of actuators. The robot fingers had three joints to imitate human fingers. One finger was driven by one wire and one servo motor for bending and by three torsion springs for extension. We also developed a soft tactile sensor having three pneumatic sensors and mounted it on front of each robot fingers. We obtained the following information from our experimental examinations of the robot hand. It adaptively grasped an object by underactuated control. The soft tactile sensor deftly touched an object, and the data showed the contact position with. By analyzing the data from tactile sensors, we obtained the rough information of the object's shape.

DNA amplification using phi29 DNA polymerase validates gene polymorphism analysis from buccal mucosa samples.

Venous blood is currently the most common source of DNA for gene polymorphism screening; however, blood sampling is invasive and difficult to perform in general dental treatment. Buccal mucosa samples provide an alternative source of DNA, but it is frequently difficult to effectively amplify the DNA owing to the small amounts of sample material obtained. This study was performed to establish a method for performing total genomic DNA amplification from buccal mucosa samples using phi29 DNA polymerase. Total genomic DNA was isolated from buccal mucosa samples obtained from healthy subjects and was amplified using phi29 DNA polymerase. To determine the suitability of the extracted DNA for genotyping, polymerase chain reaction and restriction fragment length polymorphism analyses were performed for the IL-1 gene polymorphism. Genotyping of the IL-1 polymorphism was successful using the amplified DNA from a buccal mucosa, but genotyping was unsuccessful using the unamplified control because of low DNA purity. The method of extracting DNA from a buccal mucosa is painless, simple, minimally invasive, and rapid. Genomic DNA from a buccal mucosa can be amplified by phi29 DNA polymerase in sufficient quantity and quality to conduct gene polymorphism analyses.

Prophylactic effect of lafutidine against the adverse reaction induced in rat stomach by repeated administration of 5-fluorouracil.

We examined the prophylactic effect of lafutidine, a histamine H2 receptor antagonist, on the morphological and functional derangement of the rat stomach after the administration of 5-fluorouracil (5-FU) in the absence or presence of taurocholate Na (TC). Rats were given 5-FU p. o. once daily for 5 days. After 18 hr fasting, the animals were given omeprazole to inhibit acid secretion. Under urethane anesthesia, the stomach was mounted on an ex-vivo chamber, perfused with 100 mM HCl, and both the transmucosal potential difference (PD) and gastric mucosal blood flow (GMBF) were simultaneously measured before and after exposure of the mucosa to 20 mM TC for 30 min. The 5-FU treatment lowered the basal PD with a decrease in the mucosal height and caused few haemorrhagic lesions in the stomach when perfused with 100 mM HCl for 2 hr. The 5-FU treatment had no influence on the reduced PD response caused by TC, but significantly impaired the increase in GMBF after exposure to TC, resulting a marked aggravation of gastric lesions. Lafutidine, given together with 5-FU for 5 days, significantly antagonized the deleterious effect of 5-FU on the basal PD and the GMBF response to TC, and prevented the aggravation of gastric lesions. These effects of lafutidine were not mimicked by cimetidine and disappeared due to the chemical ablation of capsaicin-sensitive afferent neurons. We conclude that 1) 5-FU treatment caused the morphological and functional derangement of the stomach and increased the mucosal vulnerability against acid, and 2) lafutidine prevents such changes caused by 5-FU treatment, probably mediated through capsaicin-sensitive afferent neurons.

GABA concentration and GAD activity levels in normal and degenerated retinas from mice.

Freeze-dried sections (14 microns thick) were prepared from mice with normal (C57BL strain) and degenerated (C3H strain) retinas. GABA concentration and GAD activity were determined in the microsamples (1.8-20 ng dry weight) of retinal layers and sublayers, using an enzymatic amplication reaction, NADP cycling. GABA was distributed over all layers of normal retina with a broad concentration peak covering both inner nuclear and plexiform layers. In contrast, GAD activity was mostly localized in the inner plexiform layer. GABA concentration was similar in one-fourth of the sublayers of each inner nuclear or plexiform layer. GAD activity was highest in the innermost sublayer of the inner nuclear layer. An increasing gradient of GAD activity was present in the inward direction in the inner plexiform layer. In the degenerated retina, lacking in photoreceptors, the inner nuclear and plexiform layers remained, and GABA and GAD levels in these layers were similar to those in normal retina.