Tsuguo Sakamoto

Experimental evidence for a vagally mediated and cholecystokinin-independent enteropancreatic reflex

: The natural history of gallstone disease in 691 patients, followed for a mean +/- SD duration of 78 +/- 61.6 months (median 62.9 months), is presented. These patients are all subscribers of a large health maintenance organization and are believed to represent a cross-section of middle income Americans. Symptoms attributed to biliary tract disease were present in 556 (80.5%), and the other 135 (19.5%) patients were asymptomatic. In the symptomatic group, the mean +/- SD duration of observation was 82.9 +/- 63.2 months (median 68.5 months); 242 (44%) eventually underwent biliary tract operations most often because of persistent symptoms. Only 10% of asymptomatic patients followed for 58 +/- 50.2 months (median 46.3 months) developed symptoms of biliary calculi, and seven per cent required operations. There were 50 deaths in this series of 691 patients, 25 in the symptomatic group, and 25 in the asymptomatic. Only two of these deaths were biliary tract related, and both were in the symptomatic group. This study suggests that patients with silent stones do not need to be operated on prior to the development of symptoms. In addition, many patients with symptoms of biliary calculi can tolerate their symptoms for long periods of time and prefer this course of action to cholecystectomy.Truncal vagotomy results in diminished pancreatic protein secretion in response to intraduodenal fat. This diminished secretion may be due, at least in part, to interruption of the vagal reflexes between the intestine and the pancreas that work independently of cholecystokinin (CCK). In five dogs with chronic pancreatic fistulas, plasma CCK concentrations and pancreatic protein secretion in response to an intestinal stimulant (intraduodenal oleate) and to two exogenous peptides (bombesin and CCK-33) were compared before and after bilateral truncal vagotomy. Vagotomy decreased integrated protein secretion by about 50% in response to intraduodenal oleate. In contrast, protein output in response to parenteral stimuli increased after vagotomy. Integrated output of CCK in response to intraduodenal oleate or to exogenous bombesin or CCK was not significantly affected by vagotomy, but release of pancreatic polypeptide was decreased significantly in response to all stimuli after truncal vagotomy. These data provide evidence that truncal vagotomy decreases pancreatic protein secretion in response to intestinal stimulants by interrupting enteropancreatic reflexes mediated by the vagus, while maintaining normal (or supranormal) sensitivity of the pancreas to endogenous and exogenous CCK.

Function of the sphincter of Oddi in patients with juxtapapillary duodenal diverticula: evaluation by intraoperative biliary manometry under a duodenal pressure load

The purpose of this study was to elucidate the function of the sphincter of Oddi (SO) in patients with juxtapapillary duodenal diverticula (JDDs). The SO function was evaluated by intraoperative biliary manometry in three groups of patients. Group 1 consisted of nine patients with JDDs and a dilated common bile duct (CBD) (diameter > 10 mm). Group 2 consisted of six patients with JDDs and a normal-sized CBD (diameter < 10 mm). Group 3 consisted of 26 patients without JDDs and with normal-sized CBDs.In the absence of a duodenal pressure load, the patients in group 1 demonstrated a lower baseline SO pressure and lower resistance of the biliary outflow than patients in group 3. They also demonstrated a lower baseline SO pressure and shorter decay time (which represented terminal biliary ductal resistance) than patients in group 2. In the presence of a duodenal pressure load of 300 mm H2O, the patients in group 1 demonstrated a lower incidence of phasic SO contractions, a higher baseline SO pressure, and a higher resistance of the biliary outflow than group 2 and group 3 patients. The decay time in group 1 and group 2 patients was higher than that of group 3 patients. Based on these findings, we conclude that the SO function in patients with JDDs is impaired owing in part to long-standing compression of the terminal biliary ductal system by a distended JDD associated with a rise in intraduodenal pressure in daily life.

Cytoprotective effect of pentagastrin and epidermal growth factor on stress ulcer formation. Possible role of somatostatin.

This study was designed to test the effects of pentagastrin and epidermal growth factor (EGF) on stress-induced ulceration and on the antral content of gastrin and somatostatin (SLI) in rats. Four groups of 14 to 15 rats had been prepared for 7 days by one of the following methods: saline injection (control); injection of pentagastrin (250 micrograms/kg, 3 times/day); injection of EGF (10 micrograms/kg, 3 times/day); or injection of EGF plus pentagastrin. At the end of the treatment period, half of each group of rats were sacrificed (nonstress group). There were no ulcers in the nonstress control groups of rats. Stress was applied by water immersion in the remaining half of the rats. The injections of pentagastrin and/or EGF resulted in substantial increase in antral content of SLI. After 20 hours of stress, the ulcer index was 40.5 +/- 3.3 in the controls, compared to 6.4 +/- 1.2 and 16.2 +/- 2.3 in rats that received pentagastrin or EGF, respectively. Injections of both pentagastrin and EGF resulted in an ulcer index of 26.2 +/- 2.0, which was significantly lower than that in controls, but higher than that in rats treated with either peptide alone. The stress resulted in significant decrease in antral SLI in all groups of rats, whereas SLI content in rats treated with pentagastrin and/or EGF remained significantly higher than that of controls. Antral content of gastrin did not differ significantly in the four groups tested. The ulcer index was inversely correlated with antral SLI content. We confirm and extend previous observations that pentagastrin and EGF prevent stress ulcer formation, and suggest that endogenous SLI may account, at least in part, for their antiulcer activity.

Release of neurotensin by selective perfusion of the jejunum with oleic acid in dogs

Plasma neurotensin concentrations are rapidly elevated after oral ingestion or intraduodenal infusion of fat, apparently before fat reaches the ileum where neurotensin is highly concentrated. The purpose of this study was to investigate the site of neurotensin release and to determine whether neurotensin is released by direct luminal stimulation by fat in conscious dogs. Dogs were prepared with isolated jejunal or ileal segments and portal vein catheters. Release of neurotensin into the portal venous blood was examined by selective perfusion of each intestinal segment with sodium oleáte. The results of this study show that selective perfusion of the jejunum, but not the ileum, with sodium oleate, caused a significant release of neurotensin. We speculate that release of ileal neurotensin is not due to direct luminal stimulation, but is mediated by local neural or humoral intermediates.

Effect of secretin on lower esophageal sphincter pressure in patients with esophageal achalasia

SummaryThe effect of a bolus intravenous administration of secretin (2.0 U/kg) on resting lower esophageal sphincter pressure (LESP) was investigated in seven patients with esophageal achalasia. Basal LESP before secretin injection in the patients was 60.113.4 mmHg (Mean±SEM), which was significantly higher than 26.9±2.5 mmHg in normal controls consisting of eight healthy volunteers. LESP significantly decreased within 1 min after the injection both in the patients and the controls. The maximum pressure change from each basal LESP was 31.2±5.2 mmHg in the patients, which was significantly greater than 12.1±1.8 mmHg in the controls. The effect of secretin disappeared within 5 min in the controls. The effect in the patients, however, lasted throughout the investigation time of 30 min. It is concluded that secretin has a long-acting effect on muscular relaxation of the lower esophageal sphincter in esophageal achalsia patients.

Gastric inhibitory polypeptide secretion after radical pancreatoduodenectomy.

To elucidate the role of gastric inhibitory polypeptide (GIP) in the alteration of insulin secretion following pancreatoduodenal resection, in which the main sources of GIP are removed, plasma levels of GIP were measured for 180 minutes after oral glucose administration, both before and after radical pancreatoduodenectomy in nine patients with periampullary cancer. Fasting plasma levels of GIP remained much the same before and after surgery, and were not different from those in normal controls. The levels of GIP after glucose ingestion were significantly greater in the preoperative patients than in normal controls throughout 180 minutes. After pancreatoduodenectomy, the postglucose levels significantly diminished but remained within normal limits. Changes in plasma levels of insulin early after glucose ingestion in these patients, however, were significantly less both before and after surgery than in normal controls, and were not concomitant with the initial increase in plasma GIP. On the other hand, plasma levels of insulin greatly increased immediately after glucose ingestion in accordance with a rapid elevation of plasma GIP in 11 gastrectomized patients in whom the duodenum and the pancreas were preserved intact and who served as the control group. Thus, the diminution in GIP secretion following pancreatoduodenectomy may relate to the lack of main sources of this gut hormone and not to factors involved in the reconstruction of the alimentary tract. We conclude that the impaired insulin secretion following oral glucose ingestion in patients before and after pancreatoduodenectomy does not relate to the secretion of GIP.

Clinical assessment of Barrett's esophagus after total gastrectomy.

Barrett様食道は下部食道粘膜が扁平上皮に代わり円柱上皮におおわれた病態である.胃全摘術施行症例に対して内視鏡検査ならびに食道粘膜生検を行った結果, 23例中5例にBarrett様食道の発生が確認された.さらにBarrett様食道は食道炎症例 (23例中13例) にのみ認められた.5例のBarrett様食道上皮は組織学的検索により全例, intestinal typeと診断された.本症の病因は先天説ならびに後天説に大別されるが詳細な発生機序は明らかでない.今回得られた事実より胃全摘術後のBarrett様食道は逆流性食道炎の臨床過程において, 吻合部に隣接する空腸粘膜が口側へ進展したものであることを示唆された.

A case of reflux esophagitis: evaluation of reflux by 24 hour monitoring of esophageal pH.

はじめに 逆流性食道炎は胃液あるいは十二指腸液の食道内逆 流により食道粘膜が障害されることにより惹起 され る。患者は胸やけ,胸 痛,逆 流感などを訴え,高 度に なると潰瘍からの出血による吐血あるいは疲痕狭窄に よる聴下困難を生じる。本症に対する内視鏡ならびに 生検による器質的診断 1ン ちあるいは食道内圧測定によ る機能的診断に関する報告めゆは数多 くみられる。しか し, これらの診断法は,逆 流現象を直接 とらえている わけでなく,本 症の病態はいまだ完全に解明されたと はいえない。 それに対し,24時 間食道 pH測 定は逆流現象を生理 的な条件下において定性的,定 量的にとらえる事が可 能であり,逆流性食道炎の正確な診断法 といえる弱。今 回,わ れわれは長期の病悩期間を有 した逆流性食道炎 の 1例 に対し,手術前後に24時間食道 pH測 定を行い, 本症の病態生理に関して若子の知見を得たので報告す る。