Noritoshi Tanida

Leukocytapheresis therapy, performed with leukocyte removal filter, for inflammatory bowel disease

Leukocytapheresis (LCAP), performed with a leukocyte removal filter, was administered five times, at 1-week intervals, for 5 weeks of intensive therapy and five times, at approximately 1-month intervals, for approximately 5 months of maintenance therapy, to 13 patients with inflammatory bowel disease (IBD) diagnosed as ulcerative colitis (UC) in 8 and Crohns disease (CD) in 5. Clinical and blood examinations showed no side effects in any of the patients. During the intensive therapy, excellent or moderate clinical response was recognized in 11 of the 13 patients (84.6%), of whom 6 had a dramatic response; the excellent or moderate clinical response continued throughout the maintenance therapy in 8 of the patients (61.5%). Flow cytometry showed that the patients who had improved generally had high values for percentages of HLADR+, HLADR+CD3+, and HLADR+CD8+ cells before the first LCAP, and that these values and the C-reactive protein levels and erythrocyte sedimentation rates had decreased to the normal range by the end of both intensive and maintenance therapy. In the patients who showed poor response, in contrast, all the above values had been at or near normal before the initial LCAP administration. The clinical improvement in the absence of any additional medical treatment suggests that LCAP has the capacity to influence the causal mechanism(s) of IBD and that IBD is strongly associated with the cell-mediated immune response.

Home elemental enterai hyperalimentation (HEEH) for the maintenance of remission in patients with Crohn’s disease

SummarySince specific treatment has not yet been decided on for Crohn’s disease, the immediate target is the induction of remission and its maintenance. We examined the effects of an elemental diet (ED) in Crohn’s disease with special reference to the maintenance of remission. Eighty-four patients received total enterai nutrition with the ED (35 to 40 kcal/kg ideal body weight/day) and/or conventional drug treatment for induction of remission. Sixty-one patients in remission were then followed-up with prolonged ED therapy (home elemental enterai hyperalimentation, HEEH) and/or drugs. During the follow-up periods the course of patients receiving HEEH was better than those of patients without HEEH, namely the cumulative continuous remission rates after one, 2 and 4 years were, 94%, 63% and 63% in the group receiving HEEH, 75%, 66% and 66% in the group receiving HEEH and drugs, 63%, 42% and 0% in the group receiving drugs, and 50%, 33% and 0% in the group receiving no maintenance therapy, respectively. In particular, when more than 30 kcal/kg ideal body weight/day of the ED was given, the maintenance of remission was successful in 95% of the patients. These results indicated that ED therapy was effective not only for the induction of remission but also for the maintenance of remission in Crohn’s disease.

Helicobacter pylori Infection Increases Mucosal Permeability of the Stomach and Intestine

It is important to study the effect of Helicobacter pylori infection on the permeability of the intestine. Permeability was evaluated by oral sucrose tolerance test using sucrose 25 g in 200 ml of water. Existence of H. pylori itself was associated with increased permeability of sucrose. Also, the permeability of sucrose increased as polymorphonuclear and lymphocyte infiltration increased. The increase of mucosal permeability suggests that antigens like protein penetrate into the body and result in systemic reactions. Thus, it is important to study the implication of increased permeability in relation not only to gastric diseases but also certain systemic diseases.

Voluntary Active Euthanasia and the Nurse: a comparison of Japanese and Australian nurses

Although euthanasia has been a pressing ethical and public issue, empirical data are lacking in Japan. We aimed to explore Japanese nurses’ attitudes to patients’ requests for euthanasia and to estimate the proportion of nurses who have taken active steps to hasten death. A postal survey was conducted between October and December 1999 among all nurse members of the Japanese Association of Palliative Medicine, using a self-administered questionnaire based on the one used in a previous survey with Australian nurses in 1991. The response rate was 68%. A total of 53% of the respondents had been asked by patients to hasten their death, but none had taken active steps to bring about death. Only 23% regarded voluntary active euthanasia as something ethically right and 14% would practice it if it were legal. A comparison with empirical data from the previous Australian study suggests a significantly more conservative attitude among Japanese nurses.

Angiomyolipoma of the colon: A new entity in colonic polypoid lesions

SummaryA 67-year-old man with angiomyolipoma on the sigmoid colon is reported. The colonic polyp was pedunculated and diagnosed histologically after endoscopic polypectomy. Angiomyolipoma is one of the benign hamartomas arising principally in the kidneys of patients with or without tuberous sclerosis. Extrarenal angiomyolipoma is rare and this may be the first report of colonic angiomyolipoma.

Fecal bile acid analysis in healthy Japanese subjects using a lipophilic anion exchanger, capillary column gas chromatography and mass spectrometry

SummaryDetailed fecal bile acid profiles of healthy Japanese subjects were studied using a lipophilic anion exchanger, capillary gas chromatography and mass spectrometry. Total daily excretion of bile acid into feces corrected for by fecal markers were between 127.99 to 366.33 μmole per day. Unconjugated bile acids constituted a major part, between 80 to 96%, of fecal bile acids. Glycine conjugated, taurine conjugated and sulfated bile acids were between 1 to 6, 0 to 3 and 1 to 10%, respectively. Esterified bile acids at C-24 position existed between 1 to 5%. Primary bile acids ranged from 0 to 55%. There were a number of epimers of hydroxy-and keto-bile acids, and lithocholic and deoxycholic acid were major secondary bile acids among them. A cholenoic acid was detected in the unconjugated fraction of one subject. It seems necessary to analyze the details not only on the type of bile acids but also on the mode of conjugation in biological samples. Thus, the methodology described in this study has made it easier to investigate on the role of bile acid in the physiology or pathophysiology of the gastrointestinal tract.

Influence of Helicobacter pylori infection on development of stress-induced gastric mucosal injury.

Abstract: Immediately after the Great Hanshin Earthquake in Kobe in 1995, the recurrence rate of peptic ulcer in patients infected with Helicobacter pylori was higher than that in patients in whom H. pylori had been eradicated. We evaluated the influence of H. pylori infection on stress-induced gastric mucosal injury in Mongolian gerbils and C57BL/6 mice. These animals were immersed in water for 30, 120, and 720 min 12 weeks after inoculation with H. pylori, and then killed to assess gastric mucosal damage, and to measure cytokine production (interleukin [IL]-1β, IL-4, IL-6, and IL-10; interferon [IFN]-γ; and tumor necrosis factor [TNF]-α) in the gastric tissue of the mice. The stress treatment for 30 min resulted in a significantly higher bleeding rate and bleeding index among infected gerbils and mice compared with results in uninfected animals. Conversely, the bleeding and ulcer indexes were significantly higher in uninfected gerbils after 720 min of the stress treatment than in infected gerbils. Prior to the stress treatment, gastric IL-1β and IFN-γ production was significantly higher in the infected group than in the uninfected group. After 120 min of the stress treatment, TNF-α production was increased in the infected group, and IL-1β and IL-10 production was increased in the uninfected group. However, the production of these cytokines showed no change at 30 min of the stress treatment. These results suggest that H. pylori infection influences the development of gastric mucosal injury in the early phase of stress exposure; cytokines do not play a major role in this process.

Campylobacter pylori in Japan: Bacteriological feature and prevalence in healthy subjects and patients with gastroduodenal disorders

SummaryThe presence ofCampylobacter pylori was investigated in biopsy specimens obtained during gastrofiberscopy from 103 consecutive patients prospectively. Patients included 25 with gastric ulcer, 4 with duodenal ulcer, 5 with coexisting gastroduodenal ulcer, 31 with gastroduodenal ulcer with gastritis, 27 with gastritis, 3 with gastric polyps and 8 with gastric cancer. Results were compared with 20 healthy control subjects who were endoscopically normal. Two specimens each were taken from 3 sites in the stomach. One part was used for a histological study to examine the presence of the organisms. The other part was cultured using Skirrow’s agar microaerophilically. Conventional microflora andC. pylori were examined in gastric contents of some cases. Bacteriological features of isolated strains of C.pylori were identical to the NCTC strain. C.pylori was the most dominant organism in gastric contents at any pH level. Detection rates of C.pylori by bacteriological culture were 96% in gastric ulcer, 100% in duodenal ulcer, 80% in coexisting gastroduodenal ulcer, 84% in gastroduodenal ulcer with gastritis, 70% in gastritis, 100% in gastric polyps and 100% in gastric cancer, and the percentages recognized by histological studies were 81,100,100, 84, 71, 67, and 57%, respectively. The values in healthy controls were 55% by histological and bacteriological methods (P<0.001 compared with overall ulcer patients). These results supported the close association between C.pylori and gastroduodenal diseases.

Effect of leukotriene C4D4 antagonist on colonic damage induced by intracolonic administration of trinitrobenzene sulfonic acid in rats

We examined the effects of eicosanoid antagonists on colonic damage induced by trinitrobenzene sulfonic acid (TNB) in a rat inflammatory bowel model. TNB (30 mg) dissolved in 0.25 ml of 50% ethanol, was given intrarectally. The appropriate doses of ONO-1078 (a leukotriene C4D4 antagonist), ONO-4057 (a leukotriene B4 antagonist), and OKY-046 (a thromboxane A2 synthetase inhibitor) were given to obtain the same blood level, either 4 h before (pre-treatment model) or 24 h after (the post-treatment model) the administration of TNB (n=8 in all groups). Drugs were given once daily for 6 days through a gastric feeding tube. Autopsy was performed on the 7th day. Colonie damage was assessed in terms of colonie damage scores, and myeloperoxidase (MPO) activity and eicosanoid concentrations in colonie tissues were measured. Compared with the group given TNB alone, the colonie damage score was reduced to 10% in the pre-treatment model with ONO-1078, but the score was not reduced in other groups, MPO activity was not changed in any group. The concentration of leukotriene C4 was reduced with ONO-1078 treatment, in both pre- and post-treatment models. These results demonstrated that a leukotriene C4D4 antagonist reduced colonie inflammation; however, its anti-inflammatory effect was limited in this colitis model.

1α-hydroxyvitamin D3 suppresses colonic tumorigenesis induced by repetitive intrarectal injection of N-methyl-N-nitrosourea in rats

The effect of 1 alpha-hydroxyvitamin D3 (1 alpha (OH)D3) on colonic tumorigenesis induced by chronic treatment with N-methyl-N-nitrosourea (MNU) was studied in rats. Seventy-four female F344 rats received an intrarectal injection of 1 mg of MNU once a week for 40 weeks. Two-thirds of rats were given concomitant administration of 0.2 ml of medium chain triglyceride (MCT) or MCT containing 0.04 microgram of 1 alpha (OH)D3 through an intragastric route thrice weekly. Numbers of rats bearing colonic tumor were 21 in MNU alone (n = 24), 17 in MNU + MCT (n = 25) and 12 in MNU + 1 alpha (OH)D3 group (n = 25) (uncorrected chi 2 = 8.72). The result indicated that colonic tumorigenesis induced by the chronic treatment with MNU was suppressed by oral supplementation of 1 alpha (OH)D3 and the inhibitory effect of 1 alpha (OH)D3 was partly due to the effect of MCT.