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Biomedical subjects

K Ishida

Publications and source records attributed to K Ishida.

At least 73 records · Page 4Linked to original sources

Paradoxical role of Helicobacter pylori infection: protective effect against ethanol-induced gastric mucosal injury in Mongolian gerbils.

We investigated the effect of ethanol (a representative necrotizing agent) on gastritis induced by Helicobacter pylori infection in Mongolian gerbils. Seventy-eight gerbils were used. Four and 12 weeks after H. pylori inoculation, 30% ethanol was administered into the stomach. The stomachs were removed after 30 min, the intramucosal prostaglandin (PG) E2 concentration was measured, and histopathology was recorded. H. pylori infection caused chronic active gastritis, gastric erosion, hypersecretion of mucin from gland mucus cells, and a rise in the activity of intramucosal PGE2. After ethanol administration, gastric erosion was significantly less in animals infected with H. pylori than in uninfected animals. In conclusion, in the early stage of H. pylori infection, accentuation of intramucosal PGE2 and hypersecretion of mucin from gland mucus cells have a protective effect against gastric mucosal injury induced by necrotizing agents.

Animals↗

Chemoradiotherapy followed by surgery for thoracic esophageal cancer potentially or actually involving adjacent organs.

The objective of this study was to evaluate the therapeutic usefulness of chemoradiotherapy (CRT) followed by surgery in patients with clinically T4 (cT4) esophageal cancer involving adjacent organs such as the trachea, main bronchi, and large vessels. Thirty-seven patients with cT4 squamous cell carcinoma of the thoracic esophagus were enrolled in this study. The CRT regimen comprised cisplatin (70 mg/m2) on day 1, 5-fluorouracil (700 mg/m2) on days 1-4 and external irradiation (200 cGy/day, total 30 Gy) on either days 8-26 (sequential schedule, n=15) or days 1-19 (concurrent schedule, n022). Two courses of CRT were given. The results of CRT were complete response in nine patients, partial response in 19, no change in three (minor response in two), and progressive disease in six patients. The median response duration in all responders was 172 days (range: 56-2469, n=19). After CRT, 13 patients received surgery. In 12 of these patients, tumors were completely resected. Histopathologic examination of the resected specimen revealed a discrepancy between clinical response and histopathologic effect. The median duration of survival and the 1-, 2- and 5-year survival rates were 304 days (84-3155), 45%, 35% and 23% in all patients, respectively, 866 days (190-3155), 83%, 83% and 57% in the 13 patients whose tumors were resected, and 187 days (84--2630), 25%, 5% and 5% in the 24 patients whose tumors were not resected. Grade 3 toxicity, especially hematological reactions, was noted in 13.5% (5/37) of the patients. There was one toxicity-related death (sepsis). A good outcome may be obtained with CRT, followed by surgery when feasible. However, CRT can cause toxic reactions, and close monitoring of patients is required.

Aged↗

Histopathological and immunohistochemical studies on arteritis induced by fenoldopam, a vasodilator, in rats.

Fenoldopam, a dopaminergic (DA1) agonist, has been reported to induce medial necrosis and adventitial inflammatory response in the splanchnic arteries in rats. This study was carried out to clarify the detailed time course of the inflammatory responses, using antibodies for the inflammatory cell markers, CD3 (T cell), CD20 (B cell) and ED-1 (macrophage), and inflammatory serum factors, IgG, IgM and C3. Rats were administered fenoldopam for 24 hours by intravenous infusion. Histopathologically, medial necrosis with hemorrhage was observed at the end of infusion, but it almost disappeared on day 7 post-infusion. Adventitial inflammatory responses with ED-1-, CD3- and CD20-positive cells were very slight at the end of infusion, became prominent with marked fibrosis on days 3 and 5, decreased on day 7, and subsided on day 14. The serum factors were first present in the area of medial necrosis, then shifted to the subendothelial space or cytoplasm of smooth muscle cells, and disappeared on day 14 post-infusion. Gaps in the external elastic lamina were observed on days 3 and 5 post-infusion, and IgG and IgM were present outside the gaps in the adventitia. These results provided us with more detailed information on the inflammatory responses following medial damage induced by vasodilators.

Animals↗

Analysis of lifestyle and behavioral characteristics in Meniere's disease patients and a control population.

A questionnaire was devised to quantify and measure four categories: the behavioral characteristics of Type A, self-restraint and escape; the causes of anxiety; means of relaxation; and symptoms incidental to anxiety. Questionnaire analysis was performed in patients (n = 60) with Meniere's disease and in a control population (n = 936). It was statistically proven that the patient group possessed a stress-causative tendency in behavioral characteristics, felt stronger anxiety and showed more severe symptoms owing to this anxiety. Since the level of anxiety highly correlates with the score of behavioral characteristics and also with severity of symptoms, it seems likely that behavioral characteristics produce the anxiety, which, in turn, results in various symptoms of autonomic nervous disorders. A tendency towards stress-causative behavioral characteristics in Meniere's disease patients may be important in the genesis of endolymphatic hydrops.

Adaptation, Psychological↗

Effect of intermittent hypoxia on cardiovascular adaptations and response to progressive hypoxia in humans.

The aim of the present study was to elucidate (1) the cardiovascular adaptations and response to hypoxic stimuli during short-term intermittent hypoxia and (2) whether the change in cardiovascular response to hypoxia is correlated to the change in hypoxic ventilatory chemosensitivity. Fourteen subjects were decompressed in a chamber to 432 torr, simulating an altitude of 4500 m, over a period of 30 min and were maintained at that pressure for 1 h daily for 7 days. Ventilatory (DeltaV(I)/DeltaSa(O2); Sa(O2) is arterial oxygen saturation), systolic and diastolic blood pressure (DeltaSBP/DeltaSa(O2) and DeltaDBP/DeltaSa(O2)), and heart rate (DeltaHR/DeltaSa(O2)) responses to progressive isocapnic hypoxia were measured before and after intermittent hypoxia. Resting ventilation, SBP, DBP, and HR did not change after intermittent hypoxia. DeltaSBP/DeltaSa(O2) and DeltaDBP/DeltaSa(O2) increased significantly after intermittent hypoxia accompanied by an enhanced DeltaV(I)/DeltaSa(C2), but there was no change in DeltaHR/DeltaSa(C2). There were significant correlations between the change in DeltaV(I)/DeltaSa(O2) and both the changes in DeltaSBP/DeltaSa(O2) and DeltaDBP/DeltaSa(O2) following intermittent hypoxic exposure. These results suggest that short-term intermittent hypoxia leads to the enhanced arterial BP response to hypoxic stimuli in humans, and that the enhanced peripheral chemosensitivity to hypoxia after intermittent hypoxia may play an important role in the increased arterial BP response.

Adaptation, Physiological↗

Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407).

BACKGROUND: Surgery for advanced esophageal carcinoma has its limits as regards aggressiveness and therapeutic effect, therefore effective multimodality treatment is required to obtain better survival. The objective of this study was to evaluate whether daily continuous infusion of CDDP could achieve a higher clinical response rate with less toxicity than its drip infusion in the previous phase II study that we had conducted. METHODS: Patients with primary extensive or relapsed esophageal carcinoma after esophagectomy, which had distant organ metastasis and histologically proven SCC, were eligible for this study. A dose of 20 mg/m(2) of cisplatin and 800 mg/m(2) of 5-fluorouracil was given by continuous infusion for 24 h on days 1-5. This treatment was repeated every 4 weeks for up to four cycles. A total of 36 men and six women with a median age of 64 (range 39-75) years were registered and 36 patients were eligible. RESULTS: The overall response rate of the registered patients was 33.3% (12/36) and the median response duration was 175 days. Median survival time was 201.5 days and the 1-year survival rate was 27.8%. Change from bolus to continuous infusion of cisplatin affected neither the type nor the degree of toxicity. CONCLUSION: Daily continuous infusion of cisplatin was not associated with higher response or lower toxicity than those seen with the high-dose bolus or multibolus treatment regimens. We conclude that this regimen in this setting is not worthy of further phase III trials. JEOG is now evaluating other drug combination regimens.

Adult↗

Factors affecting renal function in 119 985 adults over three years.

Blood pressure, proteinuria and serum creatinine (SCr) were examined in 119 985 adults, aged 40 years and older, who attended annual health examinations both in 1993 and 3 years later. Renal function was assessed from SCr; changes in individuals' renal function were estimated using the slope of the regression line for the reciprocal of the SCr level vs. time (slope of rSCr) over the 3-year period. Age-dependent SCr concentration increments were observed; however, there was no significant age-dependent change in the slope of rSCr. SCr in hypertensives on anti-hypertensive medication was significantly higher than that in untreated hypertensives, borderline hypertensives and normotensives. The slopes of rSCr in hypertensives (treated, untreated and borderline) were steeper than normotensives in males, and that in untreated hypertensives was steeper than other groups in females. In hypertensives with proteinuria, SCr was higher and renal function deteriorated more rapidly, compared with hypertensives without proteinuria. Hypertension with proteinuria appears to be an important indicator for progressive decline in renal function, this trend being more obvious in males. Renal function decreases with age; however, the rate of decline is constant. The influences of proteinuria and blood pressure on renal function are different in males and females.

Adult↗

Mathematical and optimal clustering of test points of the central 30-degree visual field of glaucoma.

PURPOSE: To determine a mathematically optimal sector pattern of the central 30 degree visual field for the follow-up of glaucomatous visual field change based on a large number of actual visual field test data of patients with glaucoma. METHODS: Visual field test data obtained from 1,039 eyes of 1,039 patients with open-angle glaucoma (OAG) using the 30-2 program of the Humphrey Field Analyzer were used for sectorization of the central 30 degree visual field. Of the 1,039 visual field data, 698 (modeling data) were used for determining the sector pattern and 341 (testing data) for checking the sector pattern. The modeling data were further divided into three groups according to the mean deviation (MD) (MD > or = -10 dB, -20 < or = MD < -10 dB, and MD < -20 dB), and the sector pattern was constructed from visual field data of each group using a clustering procedure called VARCLUS. The testing data were used for determining the optimal sector pattern. In a separate set of repeated visual field data of 303 patients with OAG, the fluctuation of MD, sector values of each sector determined, and total deviation of each test point were calculated and compared. RESULTS: The sector pattern constructed from visual field data of MD > or = -10 dB summarized the visual field performance most effectively. The fluctuation of the sector value of each sector was roughly 1.5 times smaller than the total deviation of each test point. CONCLUSION: The sector pattern determined may be useful in analyses of the visual field data of patients with glaucoma.

Glaucoma, Open-Angle↗

Presynaptic inhibition of cerebellar GABAergic transmission by glutamate decarboxylase autoantibodies in progressive cerebellar ataxia.

Autoantibodies against glutamic acid decarboxylase (GAD) have been found in stiff-man syndrome, insulin dependent diabetes mellitus, and progressive cerebellar ataxia. A patient with progressive cerebellar ataxia is described who was positive for GAD autoantibodies, and had Sjögren's syndrome. Immunohistochemical studies using CSF and serum samples from the patient showed immunoreactivities in axon terminals of cerebellar GABAergic neurons. A whole cell patch clamp technique recording from rat cerebellar slices showed that the CSF, presumably through GAD autoantibodies, presynaptically inhibited GABAergic transmission. Intravenous administration of immunoglobulin failed to improve clinical symptoms and immunoreactivities examined after therapy. The findings suggest that GAD autoantibodies play a pathogenic part in reducing GABA release in in vitro slices.

Aged↗

Intermittent hypoxia increases ventilation and Sa(O2) during hypoxic exercise and hypoxic chemosensitivity.

The purpose of this study was 1) to test the hypothesis that ventilation and arterial oxygen saturation (Sa(O2)) during acute hypoxia may increase during intermittent hypoxia and remain elevated for a week without hypoxic exposure and 2) to clarify whether the changes in ventilation and Sa(O2) during hypoxic exercise are correlated with the change in hypoxic chemosensitivity. Six subjects were exposed to a simulated altitude of 4,500 m altitude for 7 days (1 h/day). Oxygen uptake (VO2), expired minute ventilation (VE), and Sa(O2) were measured during maximal and submaximal exercise at 432 Torr before (Pre), after intermittent hypoxia (Post), and again after a week at sea level (De). Hypoxic ventilatory response (HVR) was also determined. At both Post and De, significant increases from Pre were found in HVR at rest and in ventilatory equivalent for O2 (VE/VO2) and Sa(O2) during submaximal exercise. There were significant correlations among the changes in HVR at rest and in VE/VO2 and Sa(O2) during hypoxic exercise during intermittent hypoxia. We conclude that 1 wk of daily exposure to 1 h of hypoxia significantly improved oxygenation in exercise during subsequent acute hypoxic exposures up to 1 wk after the conditioning, presumably caused by the enhanced hypoxic ventilatory chemosensitivity.

Adult↗

New antifungal 1,2,4-triazoles with difluoro(substituted sulfonyl)methyl moiety.

New 1,2,4-triazoles (2) having a difluoro(substituted sulfonyl)methyl moiety were designed and synthesized via alpha,alpha-difluoro-alpha-(substituted thio)acetophenones (3). Compounds (2) showed potent antifungal activities against C. albicans, C. krusei, A. flavus and A. fumigatus in vitro and against C. albicans in vivo for oral and i.v. administrations. Especially, (-)-2a, (-)-2b and (-)-2d showed potent antifungal activities.

Antifungal Agents↗

Blood pressure and heart rate are increased by AF-DX 116, a selective M2 antagonist, in autonomic imbalanced and hypotensive rats caused by repeated cold stress.

Rats exposed to SART (specific alternation of rhythm in temperature) stress, which are ideal animal models for vagotonia-type dysautonomia, show various changes in cardiac and circulatory systems. In this study, attention was directed to cholinergic function in the SART-stressed rat heart and the effects of AF-DX 116, a specific muscarinic M2 antagonist, on blood pressure and heart rate. The results were compared with those obtained for atropine and pirenzepine. In SART-stressed rats, systolic and diastolic blood pressures (SBP and DBP) were lower than in unstressed rats. Oral AF-DX 116 resulted in greater elevation of DBP than SBP in unstressed rats. In stressed rats, greater and more prolonged elevation of SBP than in unstressed rats was noted, particularly at higher doses. A dose-dependent SBP change in stressed rats, caused by intravenous AF-DX 116, was shifted upward in parallel with that in unstressed groups, unlike with oral administration. The positive chronotropic effect of this drug was smaller in stressed rats than in unstressed rats, in contrast to the pressor effect. SART-stressed rats may thus have an enhanced sympathetic tone in the heart, as well as changes in muscarinic M2 receptors at sympathetic nerve endings and at the heart muscle. The effects of AF-DX 116 on blood pressure and heart rate thus may arise from peripheral action and AF-DX 116 may be useful for treating hypotension related to autonomic imbalance of the vagotonia type.

Animals↗

[A breast cancer patient with recurrence in the thoracic wall in whom a high-dose of toremifene was effective].

The patient was a 53-year-old female who presented with a primary complaint of reddening of the left precordial skin. She had undergone mastectomy for cancer of the left breast 12 years and 4 months earlier and had received endocrine chemotherapy including TAM as a postoperative adjuvant therapy. A diagnosis of thoracic wall recurrence was made by chest CT and pathological examination of skin biopsy specimens. Toremifene (TOR) was administrated at 120 mg/day, and PR was maintained for 8 months. Even after the condition became PD, the patient has retained adequate QOL with combination therapies including radiotherapy, and is still treated on an outpatient basis 3 years after the beginning of the treatment.

Antineoplastic Agents, Hormonal↗

[Clinical efficacy of magnetic resonance cholangiopancreatography in the diagnosis of biliary tract diseases].

This study was carried out to clarify the efficacy of magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of biliary tract diseases, Three hundred and eleven patients who underwent MRCP and ERCP during the period from January 1999 to December 1999 at our institution were included in the study. Two gastroenterologists who were blinded to results of direct cholangiography and final diagnoses interpreted MRCP images prospectively. The biliary duct was visualized by MRCP and ERCP in 99.4% and 89.5% of the cases, respectively. The sensitivity, specificity, and accuracy of MRCP in the diagnosis of choledocholithiasis were 95%, 97%, and 97%, respectively. MRCP depicted the presence of strictures with a sensitivity, specificity, and accuracy of 97%, 96%, and 96%, respectively. There were three false-positive cases because of artifacts from arterial compression, The accuracy of MRCP and ERCP in differentiation of benign strictures from malignant ones was 85% and 96%, respectively. Based on these results, it is concluded that MRCP has high capability in visualization of the biliary tree, and in detection of stones and strictures, To avoid over and under-diagnosis, awareness of some pitfalls inherent in, MRCP is important. We suggest that MRCP should be recommended for patients with suspicion of biliary tract diseases in the initial stage of making diagnosis.

Adult↗

[Current spread of HPN and HEN: issue for making choice in home care].

Recently a number of patients have received home enteral nutrition (HEN) as well as home parenteral nutrition (HPN) in Terumo's home healthcare network 'Home-Joint'. This study was undertaken to compare the patients who received HEN with those who received HPN. 1. HPN patients in 2000. Number: 1,789 (45% females), age: 0-101 (mean: 66 years old, 48% over 70 years old), diagnosis: cancer 54%, therapeutic periods: 0-916 days (mean: 80 days). 2. HEN patients in 2000. Number: 736 (40% females), age: 1-101 (mean: 50 years old, 33% over 70 years old), diagnosis: Crohn's disease 44%, therapeutic periods 0-1,618 days (mean: 183 days). 3. Adoption of HPN and HEN in home care agents. HPN only 66%, HEN only 24%, both HPN and HEN 10%. It suggested that following two issue take place against making choice of HPN or HEN in home nutrition care. 1) Adoption of both HPN and HEN in more clinics. 2) Establishment of the guidelines for systematic HPN/HEN choice.

Aged↗

Effect of ethanol on hemorheology in patients with ischemic cerebrovascular disease and elderly healthy men.

Changes in hemorheological parameters were studied in patients with ischemic cerebrovascular disease and elderly healthy men who ingested ethanol at 0.5 and 1 g/kg body weight. Following ingestion of 1 g/kg, but not 0.5 g/kg of ethanol, there were significant changes in hemorheologic factors. Whole blood viscosity (WBV, shear rate: 18.8, 37.5, 75, 150, 350 sec(-1)) and blood viscosity corrected for hematocrit (BVC) were increased. WBV and BVC at high shear rate were increased and red blood cell deformability impaired in patients with ischemic cerebrovascular disease, while those factors were not significantly changed in healthy men. It is considered that ethanol ingestion could has bad influences for the microcirculation in patients with ischemic cerebrovascular disease.

Acetaldehyde↗