Kose Segawa

Peptic ulcer is prevalent among shift workers.

To elucidate sleep disturbances in the etiology of peptic ulcers, the prevalence of peptic ulcer disease was compared among shift workers and daytime workers. The subjects (N=11,657) were employees of various institutions, such as factories, banks, or schools, and had undergone a mass x-ray examination of the upper gastrointestinal tract. With present shift workers (N=2269), the prevalence of gastric ulcers was 2.38% (N=54) and that of duodenal ulcers, 1.37% (N=31). With the past shift workers (N=2111), the prevalence of gastric ulcers was 1.52% (N=32) and that of duodenal ulcers, 0.62% (N=13). On the contrary, with the daytime workers (N=6525) the prevalence of gastric ulcer was 1.03% (N=67) and that of duodenal ulcer, 0.69% (N=45). The working schedule for 752 examinees was unknown. The prevalence of gastric and duodenal ulcers was higher with shift workers than daytime workers. Thus, shift work involving sleep disturbances may play an important role in the development of peptic ulcers.

Effects of Prednisolone and Human Epidermal Growth Factor on Angiogenesis in Granulation Tissue of Gastric Ulcer Induced by Acetic Acid

In an attempt to elucidate the role of granulation vessels in the healing of gastric ulcer, healing and angiogenesis in granulation tissue of acetic acid ulcers were studied in rats. In addition, the effects of prednisolone and synthetic human epidermal growth factor (EGF) on angiogenesis and ulcer healing were investigated. The newly formed granulation vessels in the ulcer base were measured by means of a carmine dye infusion method. Prednisolone, administered subcutaneously at 40 mg/kg/day, significantly decreased angiogenesis in the ulcer base on the 10th day after ulcer production, and on the 30th day ulcer healing was found to be significantly delayed. In contrast, angiogenesis was significantly increased, and ulcer healing was enhanced by intragastric administration of 100 micrograms/kg/day of EGF. With combined administration of prednisolone and EGF, angiogenesis was significantly increased compared to that observed with prednisolone treatment alone. The authors conclude that suppression of angiogenesis by prednisolone is a delaying factor in gastric ulcer healing and that exogenous EGF promotes ulcer healing, partly through restoration of angiogenesis.

Effects of Cimetidine and Omeprazole on Angiogenesis in Granulation Tissue of Acetic Acid-Induced Gastric Ulcers in Rats

We investigated the effects of cimetidine and omeprazole on angiogenesis in granulation tissue and on the healing of gastric ulcers induced by acetic acid in rats. Either cimetidine (50 or 100 mg/kg) or omeprazole (10 or 20 mg/kg) was orally administered once daily for 9 consecutive days from the day following ulcer production. The ulcer index on the 10th and 30th days after ulcer production, and the extent of angiogenesis on the 10th day were examined. Cimetidine dose-dependently decreased the extent of angiogenesis on the 10th day, whereas the ulcer index on the 10th days was not significantly different between cimetidine-treated and control rats. The ulcer index of the groups treated with cimetidine during the initial 9-day period was increased compared with the control group on the 30th day. In contrast, oral omeprazole did not affect angiogenesis on the 10th day and decreased the ulcer index on both the 10th and 30th days. These results suggest that oral cimetidine may inhibit angiogenesis in ulcer granulation tissue possibly via the blocking of histamine H2 receptors and this may be one cause of delayed ulcer healing.

Monozygotic twins concordant for intestinal Behçet's disease.

Although Behçet’s disease (BD) is a multisystem disorder of unknown causes, both genetic and environmental factors have been suggested. This is the second reported case of monozygotic twins concordant for Behçet’s disease and the first such report of intestinal Behçet’s disease. Patient 1 was a 17-year-old man with fever, recurrent oral aphthae, and skin eruptions. He developed hematochezia and was given corticosteroid empirically. One month after he was discharged, he again developed oral ulcerations, fever, and hematochezia. Colonoscopy was performed again, showing aphthous ulcerations in the entire colon, and deep oval ulcers with marginal elevation around the ileocecal valve, which are characteristics of intestinal Behçet’s disease. He was treated with colchicine and azathioprine in combination with salazosulfapyridine (SASP) and prednisolone (PSL) and achieved remission. Patient 2 was the twin brother of patient 1. He was admitted because of oral aphthous ulcerations, fever, pustules on his face and body, and genital ulcers. Two weeks later he developed hematochezia. Colonoscopic and barium enema findings were similar to those of his brother. SASP, PSL, colchicines, and azathioprine were also required to achieve remission. Both of the patients were diagnosed with intestinal Behçet’s disease. Their monozygosity was confirmed by detailed genetic typing, and HLA-B51 was negative.

Effect of omeprazole on gastric acid secretion in rat: Evaluation of dose, duration of effect, and route of administration

SummaryThe effect of omeprazole on gastric acid output was studied in rats before and during stimulation by continuous administration of tetragastrin at 50 Μg/kghour. From 5 to 20 mg/kg of omeprazole was given to animals intraperitoneally, perorally and intravenously from 2 to 24 hours before the gastric secretory study was started, and the respective effects on acid secretion were compared. In each administration group, 20 mg/kg of omeprazole was the most potent among the groups receiving 5, 10 or 20 mg/kg, when the drug was given 2 hours before the study. There were statistically significant differences between the control group given tetragastrin only and each of the groups given 20 mg/kg of omeprazole perorally, intraperitoneally and intravenously. There was no significant difference among the groups given 20 mg/kg of omeprazole intraperitoneally, intravenously and perorally. The effect of 20 mg/kg of omeprazole continued at least 24 hours after the agent was administered perorally.

The Diagnosis of the Anomalous Connection of Pancreaticobiliary Ducts Without Biliary Dilatation—The Usefulness of US/EUS Serial Examination—

The anomalous connection of the pancreaticobiliary duct (ACPBD) without accompanying dilatation of the bile duct (non‐dilated type of ACPBD) has recently been found to be associated with gallbladder cancer at a rather high rate. We analyzed the diagnostic process of 5 patients with non‐dilated type of ACPBD including 3 asymptomatic cases and reviewed the literature. Symptoms and laboratory data were not useful in detecting this type of lesion. All our patients were checked by ultrasonography for gallbladder lesions which are suggested by: wall thickening, multiple polyps, intramural gall stones, cholecystolithiaisis, and debris. ACT revealed only wall thickening of the gallbladder. An EUS revealed a high rate of ACPBD in addition to the ultrasonographic findings of gallbladder lesions obtained by US. An ERCP was effective in clearly demonstrating ACPBD, but was not so useful for the diagnosis of concomitant gallbladder lesions. Therefore, an US is considered to be a useful means for screening this disease, and EUS is useful as a procedure to follow in order to select patients with or without ACPBD, because EUS can be conducted on an outpatient basis and is highly sensitive in detecting ductal anomalies in ACPBD. Therefore, the US/EUS serial examination is thought to be an effective means for diagnosing this disease.

Morphological and Functional Evaluation of Gastric Ulcer Healing and Recurrence by Endoscopic Ultrasonography

Abstract: The aim of this study was the evaluation of gastric ulcer healing and recurrence, from the viewpoints of morphology and function, by means of endoscopic ultrasonography (EUS). We determined ulcer depth by EUS and quantified ulcer size in EUS images. In addition, we measured the total gastric juice acid content after fasting and the macromolecular glycoprotein weight in antral biopsies. First, we examined 22 patients receiving initial therapy during the active ulcer stage. Fourteen of these patients were reexamined after healing. The ulcer area diminished significantly, as did the total acid content, during the scarring stage. Then, another 22 patients on maintenance therapy were followed for recurrence over a 10 month period. The recurrence rate in UI‐IV ulcers was significantly higher than those in UI‐II or III ulcers. The ulcer area was greater and the macromolecular glycoprotein content lower in patients experiencing recurrence. In conclusion, morphological and functional factors (ulcer depth and ulcer area; total acid content and macromolecular glycoprotein weight), which could be assessed easily and simultaneously using an EUS fiberscope with a biopsy channel, were useful for evaluating gastric ulcer healing and recurrence.

The effect of a new gastric proton pump inhibitor on serotonin-induced gastric mucosal lesions in rats

SummaryThe anti-ulcer effect of NC-1300, a new proton pump inhibitor, and its effect on gastric mucosal blood flow were studied in rats. Acute gastric mucosal lesions were induced by the subcutaneous administration of serotonin, 20 mg/kg. Using the electrolytically generated hydrogen gas clearance technique, it was determined that such gastric ulceration resulted mainly from a decrease in gastric mucosal blood flow. These lesions could be inhibited to a statistically significant extent by the intravenous administration of NC-1300, 20 mg/kg, which markedly inhibited gastric acid secretion. However, the serotonin-induced decrease in gastric mucosal blood flow could not be prevented by pretreatment with 20 mg/kg of NC-1300. It was concluded that protection against serotonin-induced gastric ulceration can be achieved by markedly inhibiting gastric acid secretion.

The further investigation on the gastric acid secretion in the primary hyperparathyroidism

SummaryThe gastric acid output was studied in the 11 patients of hyperparathyroidism before and after parathyroidectomy. The gastric acid output before operation was almost equal to the normal control in our hospital. After the correction of serum calcium by parathyroidectomy, the gastric acid output and serum gastrin were decreased. The decreased gastric acid output was recovered as the days passed since operation and approached to the preoperative level. The acid output in hyperparathyroidism was less in the case whose activity of alkaline phosphatase was more, which suggested that the calcium deposition on gastric mucosa might damage the parietal cell as the result of long lasting hypercalcemia.

The nocturnal intragastric pH in EEG sleep stages in peptic ulcer patients.

SummaryIn 10 peptic ulcer patients, 5 duodenal ulcer and 5 gastric ulcer patients, the relation of nocturnal intragastric pH to EEG sleep stages was examined. The nocturnal intragastric pH was monitored by pH-measuring telemeter and sleep stages were recorded simultaneously by electroencephalography throughout the night. The EEG sleep stages were classified after the criteria of Dement and Kleitman. The average of intragastric pH level at each sleep stage was higher in gastric ulcer than the duodenal ulcer. The intragastric pH level became low as the patients’ sleep advanced to deep stage. This tendency was more likely in duodenal ulcer patients than the gastric ulcer patients, which indicated that the cephalic phase might play an important role in the pathogenesis of hyperacidity in duodenal ulcer.