Noritsugu Umeda

Patients with Constipation-Predominant Irritable Bowel Syndrome (IBS) May Have Elevated Serotonin Concentrations in Colonic Mucosa as Compared with Diarrhea-Predominant Patients and Subjects with Normal Bowel Habits

Background: Serotonin (5-HT) may play an important role in the regulation of colonic motility in humans. However, it is not known whether alterations in the colonic 5-HT system are involved in the pathophysiology of irritable bowel syndrome (IBS). Methods: Colonic mucosal specimens ranging from the ascending colon to the rectum were obtained from patients with diarrhea- or constipation-predominant IBS (n = 7 and n = 8, respectively) and from subjects with normal bowel habits (n = 7) by endoscopic biopsy in order to determine whether patients with different clinical manifestations of IBS have different mucosal disposition of 5-HT. The tissue concentrations of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid, were determined by reversed-phase high-performance liquid chromatography with fluorescence detection. Results: In all study groups, the mean mucosal 5-HT concentrations obtained from the rectum were significantly (p < 0.05) higher than those obtained from more cephalic regions of the colon. In addition, the overall mean mucosal 5-HT concentrations obtained from patients with constipation-predominant IBS were significantly (p < 0.05) higher than those obtained from the control subjects and patients with diarrhea-predominant IBS. No significant differences were observed in 5-hydroxyindoleacetic acid concentrations among the three groups. Conclusions: The mucosal 5-HT concentrations in the colon showed an ascending cephalocaudal gradient in all study groups. Although the mucosal 5-HT concentrations were elevated in patients with constipation-predominant IBS as compared with those with diarrhea-predominant IBS and the control subjects, further studies are necessary to determine whether the elevated mucosal 5-HT is a cause or a result of abnormal colonic motility.

Serum hepatocyte growth factor levels in hepatectomized and nonhepatectomized surgical patients

Serum hepatocyte growth factor levels were measured in hepatectomized and nonhepatectomized surgical patients. The levels were significantly increased and reached a maximum within 7 days after surgery in both groups, returning to preoperative levels 28 days after partial hepatectomy and 7 days after other operations. Multiple regression analysis showed that such maximal hepatocyte growth factor levels were significantly related to having liver cirrhosis and postoperative maximal serum total bilirubin and alanine aminotransferase levels and peripheral white blood cell counts in the hepatectomized group and to postoperative maximal peripheral white blood cell counts and serum C-reactive protein levels in the nonhepatectomized group. However, the levels showed no relation to the resected liver volume and increment of the remaining liver volume 28 days after partial hepatectomy. It is concluded that serum hepatocyte growth factor levels were increased after partial hepatectomy in association with hepatocellular dysfunction and necrosis and systemic inflammation. It is unlikely that the increase was related to liver regeneration.

Outcome of gastric carcinoma detected by gastric mass survey in Japan.

The outcome was studied of gastric carcinoma found in six selected mass survey groups. One-hundred-and-thirty-seven cases of gastric carcinoma were detected and followed-up postoperatively for 16 years at the longest. They consisted of 55 cases of early and 74 of advanced carcinoma with eight cases of unknown depth of involvement. Early carcinoma amounted to 42-6% of the cases with known depth of involvement. The relative five-year and 10-year survival rates calculated by the method of Ederer et al. (1961) in the 137 cases were 0-628 and 0-642, respectively, and those for early carcinoma were 0-959 and 1-016. These survival rates are remarkably high. The five-year survival rate in those who were followed-up after operation for more than five years (83 cases) was 0-554, which is much higher than that of the outpatient cases, who presented themselves for medical advice with some symptoms. The good prognosis is largely explained by a high incidence of early gastric carcinoma in the cases detected in the mass survey. Where methods of screening were concerned, the use of the gastrocamera markedly improved the detection rate of gastric carcinoma.

Effects of Subchronic Treatment with Natural Human Interferons on Antipyrine Clearance and Liver Function in Patients with Chronic Hepatitis

To determine whether natural human interferon administered under the usual therapeutic dosing scheme would inhibit the hepatic drug metabolism, we performed an antipyrine test in eight patients with chronic B or non‐A, non‐B hepatitis before and after a subchronic interferon therapy (6 megaunits/day for 17 ± 4 days, mean ± SD). Six patients received interferon‐β and 2 received interferon‐α. To circumvent a possible influence of interferon‐induced fever on the hepatic drug metabolism, the antipyrine test during the interferon therapy was performed at least 14 days after the interferon‐induced fever disappeared. The kinetic parameters of antipyrine were obtained from seven saliva samples over 32 hours postdose. There were no significant differences in any kinetic parameters of antipyrine observed before and during the interferon therapy. With the sample size of the study, there was only a 20% chance (i.e., β‐power = 0.8 at α = 0.05) that we might have missed a 17% reduction in antipyrine clearance by the interferon therapy (type II error). On the other hand, the subchronic interferon therapy lowered serum aminotransferases and DNA polymerase activity significantly (P < .05) compared with the respective baseline values. Our results suggest that the subchronic therapeutic dosing scheme of interferon as conducted in the present study does not cause the inhibitory effect on the oxidative drug metabolism to a statistically significant or clinically relevant degree in patients with chronic hepatitis, while it improves their liver function. Further studies are required for determining if different types of interferons administered under the different dosing schemes would alter the hepatic drug metabolism and the inhibitory effect would be time‐dependent.

Marked clinical improvement in patients with hepatocellular carcinoma by surgical removal of extended tumor mass in right atrium and pulmonary arteries

Two patients with advanced hepatocellular carcinoma presented severe exertional dyspnea because of extension of a tumor into the right side of the heart. Removable of the tumor thrombus by open-heart surgery ameliorated the symptoms in each case, but their subsequent courses differed considerably. One patient survived for as long as 8 months thanks to successive multidisciplinary treatments, whereas the other patient died suddenly 1 month after the surgery. The first patients hepatocellular carcinoma was more differentiated, and the dyspnea was caused by a low cardiac output due to the intracardiac tumor mass, not by pulmonary embolism as in the second patients case. We conclude that successive multidisciplinary treatments to control the growth of hepatocellular carcinoma is the most important approach and is indispensable for improving the prognosis.

Lansoprazole versus famotidine in symptomatic reflux esophagitis: a randomized, multicenter study.

We compared the usefulness of lansoprazole and famotidine for treatment of reflux esophagitis. Fifty-four subjects with moderate to severe reflux esophagitis were divided into two groups. The lansoprazole group (LPZ) received lansoprazole 30 mg once daily for 4 weeks, followed by famotidine 20 mg twice daily for 4 weeks. The famotidine group (FAM) received the same medications in the reverse order. Patient evaluation was based on six factors found on endoscopy, and on patient reports of heartburn. Evaluations were done before the start of the study and at 4 and 8 weeks. The improvement rates in the grade of GI classification at 4 weeks were 57.7% in the LPZ group and 38.5% in the FAM group; there was no significant difference between the two groups. However, after drugs were switched, more patients who switched to famotidine experienced a deterioration of their condition than did those who switched to lansoprazole. The percentages of “useful” or “very useful” were not significantly different between the two groups, but the percentage of “very useful” in the LPZ group (46.2%) was significantly higher than that in the FAM group (14.3%) (p<0.05). These results suggest that lansoprazole is the first drug of choice for treatment of moderate to severe reflux esophagitis.

Catecholamine concentrations in biopsied gastroduodenal tissue specimens of patients with duodenal ulcer

We measured dopamine and norepinephrine concentrations in the biopsied gastroduodenal mucosa obtained from 12 ulcer-free dyspeptic patients, nine patients with active duodenal ulcer, and eight patients with inactive (or healed) duodenal ulcer using a high-performance liquid chromatography with electrochemical detection method. Biopsy specimens were taken from endoscopically normal-appearing mucosa in the gastric body and antrum as well as in the duodenal bulb. Additional specimens were obtained from the outer edge of the ulcer margin in patients with active duodenal ulcer. The mean (±SD) mucosal dopamine concentrations in the gastric body and duodenum (7.6±2.8 and 6.8±2.6 pg/mg tissue) obtained from patients with inactive duodenal ulcer were significantly (P<0.05) lower than those from dyspeptic patients (13.6±6.9 and 10.9±3.5 pg/mg tissue, respectively). In contrast, no significant differences were observed in the mean norepinephrine concentrations in these gastroduodenal tissues among the three study groups. However, the mean mucosal norepinephrine concentration in the outer edge of duodenal ulcer (86.2±125.6 pg/mg tissue) was significantly (P<0.05 and 0.01) reduced as compared with that in the ulcer-free area of duodenum obtained from patients with inactive duodenal ulcer (257.1±188.2 pg/mg tissue) and from dyspeptic patients (276.8±138.3 pg/mg tissue). The results suggest that an alteration in the catecholaminergic system may be associated with one of the pathogenic factors of duodenal ulcer.

Double Cardia An Unusual Sequela of Reflux Esophagitis with Ulcer

SummaryWe report a patient with acquired “double cardia” (esophagogastric fistula). She was a 76-year-old farmers widow with severe kyphosis. She presented with postprandial heartburn one month after the initiation of nifedipine and isosorbide dinitrate. Radiologic and endoscopic examinations revealed an esophagogastric fistula, short esophagus with hiatal hernia, Barretts esophagus with reflux esophagitis, and ulcer. This case shows that repeated reflux esophagitis and esophageal ulcer, complicated with short esophagus and hiatal hernia, can predispose to the formation of esophagogastric fistula.

Lansoprazole for maintenance therapy of peptic ulcer disease: weekend full-dose or everyday half-dose administration?

Seventy-one patients with peptic ulcer (44 gastric ulcer and 27 duodenal ulcer patients) were enrolled in this study. After the ulcers had healed with 2 months of treatment with lansoprazole (LPZ) 30 mg/day, patients were divided into two groups: 43 in the half-dose q.d. group and 28 in the weekend full-dose group. Fourteen (23%) of the 43 patients in the half-dose q.d. group and 14 of the 28 (50%) in the weekend full-dose group failed to continue taking the drug for 6 months owing to poor compliance (p < 0.05). None of the 30 patients who continued to take the maintenance dose of LPZ experienced ulcer recurrence during the 6-month follow-up period, whereas 71% of the patients who stopped taking LPZ experienced recurrence (p < 0.01). In conclusion, maintenance therapy using the half-dose q.d. administration schedule was superior to weekend full-dose administration because of the better patient compliance and a lower ulcer recurrence rate.

Raised plasma concentrations of 3-methoxy-4-hydroxyphenylethyleneglycol in cirrhotic patients with or without hepatic encephalopathy.

We measured the plasma concentration of a centrally derived noradrenaline (NA) metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), in 20 cirrhotic patients (eight with (group A) and 12 without (group B) hepatic encephalopathy (HE] and in 14 age matched healthy subjects to study if the central NA metabolism would be altered in liver cirrhosis patients, particularly in those with HE. The mean (SEM) plasma MHPG concentrations in the patient groups, group A (74.9 (8.6) pmol/l) and B (54.8 (7.2) pmol/l), were significantly (p less than 0.01) greater than in the control group (22.3 (2.0) pmol/l), and that in group A was significantly (p less than 0.05) greater than in group B. The plasma concentration of MHPG observed in these study subjects (n = 34) correlated (rs = 0.77, p less than 0.01) more strongly with the ratio of plasma catecholamine precursor amino acids (tyrosine and phenylalanine) to other neutral amino acids (tryptophan, leucine, isoleucine, and valine) known to compete with catecholamine precursor amino acids for uptake into the brain than with plasma concentration of tyrosine plus phenylalanine alone (rs = 0.63, p less than 0.01). In addition, the mean plasma MHPG concentrations measured in another group of eight cirrhotic patients (group C) during HE (79.3 (10.6) pmol/l) was significantly (p less than 0.01) greater than that measured after the recovery from HE (47.2 (5.2) pmol/l). The results suggest that the central NA metabolism may be altered in patients with liver cirrhosis, particularly in those with HE, and that the derangement in the central NA metabolism may be associated not only with an increase in plasma catecholamine precursor amino acids but also with a decrease in branched chain amino acids.