Abnormal pontine activation in pathological laughing as shown by functional magnetic resonance imaging.

To explore the aetiology of pathological laughing, a 65-year-old woman with pathological laughing was examined by 3-T functional magnetic resonance imaging (fMRI) before and after treatment with drugs. Here, we report that the patient consistently showed exaggerated pontine activation during the performance of three tasks before treatment, whereas abnormal pontine activation was no longer found after successful treatment with the selective serotonin reuptake inhibitor, paroxetine. Our findings in this first fMRI study of pathological laughing suggest that serotonergic replacement decreases the aberrant activity in a circuit that involves the pons.

Adverse effects of energy restriction on changes in immunoglobulins and complements during weight reduction in judoists.

AIM: A preliminary study to investigate the combined effects of dietary restriction and weight reduction through exercise on markers of immune function in college judoists before and after a single competition. METHODS: Forty-nine judoists participated in the study. Thirty-eight athletes combined exercise and dietary restriction (WR group), and 11 athletes did not require dietary restriction (EX group). Changes in anthropometric parameters, energy intake, concentrations of serum immunoglobulins and complements, and white blood cell counts were assessed at 4 time points: 20 days (pre-values), 4 days and 1 day before the competition, and 7 days after the competition. RESULTS: Compared with pre-values, the WR group exhibited significant decreases in body weight (-2.8 kg at 1 day before) and fat free mass (-1.7 kg at 1 day before); there were no changes in these variables in the EX group. The WR group exhibited significant decreases in IgG, IgM and C3 at 7 days after the competition (all p<0.01). In the EX group, significant decreases in IgM and C3 (both p<0.05) were observed at 7 days after the competition, though to a lesser degree than in the WR group. CONCLUSIONS: Energy restriction seemed to exacerbate alterations in immune markers such as immunoglobulin and complement induced by vigorous exercise at 7 days after a competition. Although the changed values were still within normal limits, we hypothesize that the potential cumulative effect of these changes over many competitions in 1 year might well induce abnormal levels with a possibly harmful clinical effect on judoists.

Dietary fiber showed no preventive effect against colon and rectal cancers in Japanese with low fat intake: an analysis from the results of nutrition surveys from 23 Japanese prefectures.

BACKGROUND: Since Fuchs' report in 1999, the reported protective effect of dietary fiber from colorectal carcinogenesis has led many researchers to question its real benefit. The aim of this study is to evaluate the association between diet, especially dietary fiber and fat and colorectal cancer in Japan. METHODS: A multiple regression analysis (using the stepwise variable selection method) was performed using the standardized mortality ratios (SMRs) of colon and rectal cancer in 23 Japanese prefectures as objective variables and dietary fiber, nutrients and food groups as explanatory variables. RESULTS: As for colon cancer, the standardized partial correlation coefficients were positively significant for fat (1,13, P = 0.000), seaweeds (0.41, P = 0.026) and beans (0.45, P = 0.017) and were negatively significant for vitamin A (-0.63, P = 0.003), vitamin C (-0.42, P = 0.019) and yellow-green vegetables (-0.37, P = 0.046). For rectal cancer, the standardized partial correlation coefficient in fat (0.60, P = 0.002) was positively significant. Dietary fiber was not found to have a significant relationship with either colon or rectal cancers. CONCLUSIONS: This study failed to show any protective effect of dietary fiber in subjects with a low fat intake (Japanese) in this analysis, which supports Fuchs' findings in subjects with a high fat intake (US Americans).

A multicenter, double-blind study on triple therapy with lansoprazole, amoxicillin and clarithromycin for eradication of Helicobacter pylori in Japanese peptic ulcer patients.

BACKGROUND: Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of Helicobacter pylori were studied in multicenter, double-blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori-positive active gastric ulcers or duodenal ulcers. METHODS: Patients were randomly chosen for the control treatment of LPZ 30 mg twice a day (b.i.d.; Group A-LPZ-only) or the test treatments of LPZ 30 mg plus AMPC 750 mg and CAM 200 mg b.i.d. (Group B-LAC200) and LPZ 30 mg, AMPC 750 mg and CAM 400 mg b.i.d. (Group C-LAC400). All eradication treatments lasted for a period of 7 days. Successful eradication was assessed by culture and gastric histology 1 month after completion of the ulcer treatment. RESULTS: The eradication rates of H. pylori in the full analysis set were 0% in Group A-LPZ-only, 87.5% in Group B-LAC200 and 89.2% in Group C-LAC400 for gastric ulcer and, 4.4% in Group A-LPZ-only, 91.1% in Group B-LAC200 and 83.7% in Group C-LAC400 for duodenal ulcer. The eradication rates of Group B-LAC200 and Group C-LAC400 were 89.2% (95% CI: 84.8-93.7%) and 86.4% (95%CI: 81.5-91.3%) in total in the full analysis set, 89% (95% CI: 84.3-93.7%) and 85.3% (95%CI: 80.1-90.5%) in the per protocol set. The eradication rates in Groups B-LAC200 and group C-LAC400 were statistically significantly higher than the rate in Group A-LPZ-only for both gastric ulcer and duodenal ulcer patients (p <.0001 for both). CONCLUSION: A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg, AMPC 750 mg, and CAM 200 mg b.i.d.

Effect of sodium butyrate on reactive oxygen species generation by human neutrophils.

BACKGROUND: Short-chain fatty acids enema has been shown to be effective in the treatment of ulcerative colitis (UC). However, the mechanisms that lead to this response have not been well characterized. The aims of this study were to investigate the effect sodium butyrate has on reactive oxygen species (ROS) generation by human neutrophils, which are responsible for mucosal injury. METHODS: Human neutrophils incubated with or without sodium butyrate were stimulated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA). ROS generation was largely differentiated with flow cytometry assays of hydroethidine oxidation and dichlorofluorescein oxidation for superoxide anion and hydrogen peroxide respectively, and luminol-dependent chemiluminescence for myeloperoxidase-mediated oxidants. RESULTS: Sodium butyrate (up to 50 mM) did not alter hydroethidine oxidation upon stimulation of the OZ or PMA. However, sodium butyrate at a concentration of 25 mM elevated dichlorofluorescein oxidation to 125 + 8% (P = 0.028) of control upon stimulation of OZ and to 191 +/- 30% (P = 0.0016) upon stimulation of PMA. Contrary to these results, sodium butyrate greatly inhibited chemiluminescence responses in a dose-dependent manner. The inhibition by 50 mM sodium butyrate was 61 +/- 6% upon OZ and 71 +/- 9% upon PMA, respectively. CONCLUSIONS: These data indicate that sodium butyrate up-regulates hydrogen peroxide generation but down-regulates generation of myeloperoxidase-mediated oxidants, the latter being more potent in killing microorganisms and in inducing tissue injury. A possible mechanism is suggested whereby sodium butyrate may inhibit myeloperoxidase activity and hence attenuate the destructive activities of neutrophils in UC.

Exercise training and energy restriction decrease neutrophil phagocytic activity in judoists.

PURPOSE: To investigate the effects of weight reduction as the result of exercise training and energy restriction on neutrophil function. METHODS: Eighteen male competitive college judoists participated in the study. In a whole blood assay, oxidative burst activity, phagocytic activity, expressions of Fc gamma receptor 3 (CD16), and complement receptor 3 (CD11b) of neutrophils were measured on a per cell basis by flow cytometry at day 20, 5, and 1 before and at day 7 after the competition. RESULTS: The rate of neutrophil producing reactive oxygen species decreased before the competition, whereas the oxidative burst activity per cell increased significantly in all subjects, which resulted in a significant increase of the total oxidative burst activity. However, there were no significant effect of energy restriction on oxidative burst activity. The rate of neutrophils incorporating opsonized zymosan decreased significantly with energy restriction. The total phagocytic activity of 10,000 neutrophils and the phagocytic activity per cell also decreased significantly by severe energy restriction. The surface antigen expressions of CD11b and CD16 were unaffected by weight reduction. CONCLUSIONS: The results suggest that with respect to the management of health conditions, weight reduction for judoists should be composed of exercise training and energy restriction should be moderate.

Relationship between mineral and trace element concentrations in drinking water and gastric cancer mortality in Japan.

It is well known that the incidence and mortality from gastric cancer in Japan are the highest in the world. This is thought to be due, in part, to dietary habit, including a high salt intake. There are, however, no epidemiological reports to describe the relationship between ingestion of mineral and trace elements and gastric carcinogenesis. In this study, we determined the concentrations of 14 elements in drinking water from 34 water treatment plants in Aomori Prefecture, Japan, and studied how element concentrations were geographically associated with gastric cancer mortality rate. Gastric cancer mortality was calculated from the data of the Annual Aomori Health Report. Multiple regression analysis (stepwise method of decreasing the number of variables) was performed by using age-adjusted mortality of gastric cancer by gender as objective variables and each element concentration as an explanatory variable. The standardized partial regression coefficient was significant in men for zinc (-0.59, P = 0.004), lead (1.01, P = 0.013), strontium (1.23, P = 0.007), and selenium (-1.62, P = 0.004), whereas it was significant in women for lead (-0.65, P = 0.022), strontium (0.51, P = 0.035), and gold (0.70, P = 0.019). It is suggested that selenium and zinc may aid in the prevention of gastric carcinogenesis. However, the significant relationship of sodium (a component of salt) to gastric carcinogenesis was not observed, although many previous epidemiological studies in Japan have shown this relationship.

Development of the membrane autotransfusion system prototype-II: MATS-II.

This article is the second of a two-part series describing a membrane autotransfusion system, MATS, utilizing plasmapheresis technology. Based on experiences obtained from the first prototype (MATS-I), optimum blood filtration parameters with refined blood and flux pump synchronization were put into an original CPU-board and loaded on a miniaturized, self-operative, and preclinical prototype (MATS-II). This study was conducted to evaluate the MATS-II using diluted blood of various hematocrit concentrations. The results proved that this device could concentrate 4,000-10,000 ml of various hematocrit concentrations into higher than 40% while automatically controlling the flow speed from 250 to 400 ml/min. Also, no significant damage was generated to the red blood cells (RBC). Moreover, the MATS-II salvaged over 90% of platelets together with the RBC. These results suggest that the MATS-II achieves all clinical requirements of an autotransfusion device; it is a continuous hemoconcentration device with minimum damage to cellular components of the blood.

In vitro evaluation study of the membrane autotransfusion system experimental prototype: MATS-I.

Membrane Autotransfusion System (MATS) utilizing plasmapheresis technology has been developed in our laboratory. A specially designed polyethylene hollow fiber membrane was utilized. This study was conducted to evaluate performance of the first experimental prototype, MATS-I. The results of this study showed that the MATS-I could concentrate diluted blood at 10% of the initial hematocrit concentration (HCTi) into over 40% after passing through the system at a transmembrane pressure of 70 mm Hg. Moreover, the MATS-I can continuously treat 10,000 ml of diluted blood at various HCTi levels without deteriorating its performances. Even though the MATS-I met all required performances as an autotransfusion system, several areas of improvement of the system were necessary to meet various clinical needs. The next prototype, MATS-II, can be designed based on experiences obtained from the MATS-I. The MATS is smaller, more atraumatic and continuous, and is a faster system when compared to the currently available centrifugal autotransfusion devices.

Preliminary evaluation study of a prototype hollow fiber membrane for the continuous membrane autotransfusion system.

A totally new autotransfusion system has been developed utilizing a hollow fiber membrane, based upon plasmapheresis technology. Prior to fabricating the system, it was essential to evaluate the basic performance characteristics of the filter, which was designed particularly for the new system. The objective of this study was to prove or disprove that such a system would be available using this filter. An in vitro study was conducted on the filter using bovine blood. The result of the study showed that the filter could process 2-20% of hematocrit blood at a flow rate greater than 250 ml/min of inlet blood continuously. Moreover, it could concentrate 5-20% hematocrit blood to hematocrit percentages greater than 40% by a single passage through the filter. These results seemed to prove that a rapid, continuous, and compact autotransfusion system could be developed using this filter.

Exacerbated autoimmune hepatitis successfully treated with leukocytapheresis and bilirubin adsorption therapy.

A 58-year-old man with subacute fulminant onset of autoimmune hepatitis (AIH) was treated by leukocytapheresis (LCAP) and bilirubin adsorption therapy (BAT), rather than by administration of high-dose corticosteroids as he had mild glucose intolerance, and a definitive diagnosis of AIH was not obtained on admission; further, there was a risk of viral infection. After initiation of the therapies, serum transaminases and bilirubin, immunoglobulins, anti-nuclear antibodies, and rheumatoid factor decreased rapidly, as did the initially high levels of activated cells and several pro-inflammatory cytokines. Liver inflammation observed on liver biopsy settled during the course of the therapies, with no adverse side effects. A pause in the therapies was associated with deterioration; however, restoration of apheresis was followed by normalization. Remission was sustained throughout the period monitored, except for a recurrence 14 months after discharge, which was successfully resolved by two additional LCAP sessions. These results suggest that LCAP influences the causal mechanism(s) of exacerbation of AIH.

[Remission by leukocytapheresis for a patient with ulcerative colitis found refractory by conventional drug therapies].

A 40-year-old male was admitted to our hospital on August 30, 1994 to receive a new ulcerative colitis (UC) therapy, leukocytapheresis (LCAP). On the admission day, he had bloody stool 5 to 6 times/day, abdominal pain, slight fever, and hypoproteinemia. His UC type was moderately severe left-sided colitis with pseudopolyposis. Prior to admission to our hospital, his condition had not improved for about 9 months, despite drug therapies such as salicylazosulphapyridine, intravenous high dose prednisolone, protease inhibitor, intraarterial hydrocortisone sodium succinate, 4 series of pulse therapies with metylpredonisolone, enema of corticosteroid, azathioprine (Imuran), and cyclosporine at another hospital. Thus he was introduced to our college hospital and treated by LCAP since September 1. After 10 LCAP sessions, remission was observed and the patient discharged on December 23. Until he was later operated on for heavy bleeding after he had discontinued treatment and had drunk heavily, he had maintained remission for 13 months with LCAP only once a month even after we gradually decreased the other medical supports and stopped all of them. After LCAP, the normalization of high percentage of leukocytes presented HLADR+ and lymphocytes presented CD 11 a+ CD 8+ was also observed. This suggests LCAP intercepts the excess immune reaction in UC by removing leukocytes.

Efficacy of nutritional therapy for active Crohn's disease.

We investigated the effect of nutritional therapy with an elemental diet (ED) for active Crohn's disease. One hundred and thirty-nine patients with Crohn's disease were enrolled in this study. Remission was judged to be present when the International Organization of Inflammatory Bowel Disease score was < or = 1 and the CRP and ESR values were within the respective normal ranges. An amount of 30kcal per 1kg of ideal body weight (IBW) per day was administered enterally, and the effect on the induction of remission in relation to various patient background factors, such as disease type, history of bowel resection, and the presence/absence of complications, was determined. An excellent remission rate was achieved in those patients to whom an adequate amount of ED could be administered. Remission rates were lower in the patient groups with any of the following complications: stenotic bowel lesions, abdominal masses, fistulas, and anal lesions. Even in those groups in which stenotic lesions or abdominal masses were present, when adequate amounts of ED could be administered, the remission rate did not differ from that in the groups without these complications. The remission rates in the groups with and without fistulas at any site, including fistulas in the anal region, were 40.0% and 82.5%, respectively, with remission being considerably easier to achieve in the patients without fistulas. Similarly, remission was difficult to achieve when anal lesions were present. These results suggest that, for active Crohn's disease, nutritional therapy with ED ( > or = 35kcal/kg IBW) should be enthusiastically administered, and in patients in whom the presence of complications necessitates therapy for 3 months or more, this point be considered to indicate a possible surgical approach.

[Pre- and post-operative adjuvant chemotherapy of colorectal cancer. Part 1. Drug concentration in tissues following UFT administration].

The concentration of Tegafur, 5-FU and Uracil in tumor and normal tissue were measured in 47 colorectal cancer patients who had been administered UFT (400/mg) for seven days before operation. The concentration of Tegafur, 5-FU and Uracil in tumor was higher than in normal tissue (p less than 0.01), and the concentration of 5-FU was correlative to the concentration of Tegafur and Uracil in both tissues. The Dukes group and histological type were not related to the concentration of Tegafur, 5-FU and Uracil in either tissue. The uptake of each drug was good and high in tumor tissue.

Granular cell tumor of the ascending colon: a case report.

A granular cell tumor (granular cell myoblastoma) of the ascending colon in a 48-year old male is reported. The tumor was detected by barium enema study as a sessile polyp, and colonofiberscopy revealed submucosal tumor. It was removed by endoscopic polypectomy. Macroscopic examination showed the characteristic features of granular cell tumor. The avidin-biotin-peroxidase complex (ABC) method for detection of S-100 protein demonstrated that the cytoplasm of tumor cells and the pleomorphic nuclei were strongly stained with anti-S-100 protein serum, which supports the concept of the Schwann cell origin of granular cell tumor.