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PURPOSE: Ischemic colitis develops after a sudden decrease in colonic blood supply and has a variety of clinical manifestations. The aim of this study was to assess the role of platelet activating factor in the pathogenesis of ischemic colitis with use of the platelet activating factor antagonist TCV-309. METHODS: Rats were randomly divided into four groups. Rats in Group RV underwent ring attachment around the rectum to induce partial obstruction and ligation of the marginal vessels of the left colon. As control, rats in Group R underwent the ring attachment and rats in Group V underwent the vascular ligation. Rat in Group C underwent sham operation. The effects of TCV-309 on lesion formation in the colon were evaluated. Thiobarbituric acid reactant level was determined in colonic mucosa, and the incidence and severity of ischemic lesions were also determined. RESULTS: Lesions of colitis were frequently observed in Group RV. TCV-309 did not prevent lesion formation, nor did it suppress the increase in thiobarbituric acid reactant level in Group RV. However, TCV-309 mitigated the severity of the lesion. CONCLUSIONS: Partial obstruction of the colon tends to induce ischemic colitis, and additional ischemia completes lesion formation. Platelet activating factor may play a role in the progression of ischemic lesions.

Patients with "reflux" gastritis after gastrectomy suffer from a variety of symptoms, and this type of gastritis may sometimes compromise the quality of life of these patients. Since Helicobacter pylori is considered to be one of the most important pathogenetic factors in gastritis, the association between H. pylori and reflux gastritis was investigated in this study. A total of 145 patients with gastrectomy were entered into the study. Five biopsy specimens from the gastric remnant were taken at upper gastrointestinal endoscopy. One specimen was examined pathohistologically, and the remaining four were examined for H. pylori infection. Fifty-two patients (36%) demonstrated H. pylori infection. The prevalence of H. pylori was significantly higher in patients who had a partial gastrectomy, and it was significantly lower in patients who had undergone gastrectomy more than 4 years previously. The histologic gastritis score in patients with H. pylori infection was significantly higher. Furthermore, H. pylori was eradicated in patients with some symptoms of gastritis and no bile reflux to the residual stomach at endoscopy; in these patients the symptoms were relieved and the histologic gastritis score decreased significantly. In conclusion, possible involvement of H. pylori is suspected in the pathogenesis of "nonreflux" gastritis after gastrectomy.

For the better pathophysiological understanding of ischemic colitis, a clinical analysis of 24 cases of this disease in a 13-year period from 1979 to 1992 was conducted. The distribution of ages was 19-89 and there were 9 males and 15 females. As to disease type, transient type was noted in 15 cases, stricture type in 5 cases, and gangrenous type in 4 cases. Most of them had some underlying diseases. Eighteen patients had bowel diseases which increased the intraintestinal pressure, and 7 patients had cardiovascular diseases. These patients first manifested abdominal pain or melena in a relatively high frequency. The diagnosis was made mostly based on colonoscopic findings in transient type of patients; barium enema in stricture types; and operative findings in gangrenous types. Conservative treatment was performed in 17 patients, elective operation in 2 patients, and emergency operation in 5 patients. It has been emphasized that ischemic colitis has a close relation with cardiovascular diseases. However, our results suggest that ischemic colitis has a close relation with the increased intralumenal pressure of the bowel as well as cardiovascular disorders.

症例は53歳の女性.1991年2月右下腹部痛を自覚して近医を受診し,注腸検査で回盲部に潰瘍性病変を認め,外来でfollow upしていたが,1993年3月中旬から右下腹部痛が増強するとともに腫瘤を触知するようになった.精査の結果,回盲弁に騎乗する下掘れ性の円形潰瘍を認め,CT・MRI検査では回盲部腸管がほぼ全周性に壁肥厚しており,血管造影検査では回結腸動脈領域の新生血管増生を認めたが広狭不整等の悪性所見は見られなかった.2年間の経過で回盲部の狭窄が著しく進行していたため手術適応ありと判断し,回盲部切除術を施行した.回盲部単純性潰瘍は比較的まれで,他の回盲部疾患との鑑別診断が重要であるが,とくに腸型べーチェット病との鑑別は困難で,内科的治療に抵抗し手術後の再発も高率で充分な経過観察が必要とされている.

The influence of 16,16-dimethyl prostaglandin E2 (16,16-dm PGE2; an agent used for the prevention of stress ulcer after hepatectomy of the cirrhotic liver) on liver regeneration after hepatectomy was studied in rats. The following results were obtained. Ulceration after the stress of 6 h of water immersion was markedly suppressed in rats treated with 30 r/kg of 16,16-dmPGE2 as compared with the untreated controls. In animals that received hepatectomy alone, the gastric pH and gastric mucosal blood flow showed significant reduction from the preoperative levels. In animals that received hepatectomy plus 16,16-dmPGE2 treatment the postoperative reduction in the gastric pH and gastric mucosal blood flow was suppressed, suggesting the effectiveness of 16,16-dmPGE2 treatment in the prevention of stress ulcer after hepatectomy of the cirrhotic liver. The 3H-thymidine uptake percentage and thymidine activity 24 h after hepatectomy and the DNA content 30 h after hepatectomy were significantly higher in animals treated with 16,16-dmPGE2 than in the untreated controls. In animals that were treated intraperitoneally with 50 mg/kg of indomethacin 6 h before hepatectomy the mitotic index 30 h after hepatectomy was markedly lower than that in untreated controls. This indomethacin-induced reduction in the mitotic index tended to be normalized by treatment with 16,16-dmPGE2. These results suggest that 16,16-dmPGE2 treatment effectively prevents stress ulcer and favorably affects hepatic regeneration after hepatectomy of the cirrhotic liver.

We investigated the response of gastric vessels to prostaglandin (PG) E2 after intra-duodenal release of bile in rats with obstructive jaundice. The animals were divided into four groups according to duration of bile duct obstruction (BDO): control and 1 week (W), 2W, and 3W groups. Prolonged BDO decreased gastric mucosal blood flow (BF) significantly. The BF recovered after the release of BDO in the 1W and 2W groups, but not in the 3W group. BDO decreased PGE2 content in gastric mucosa in the 1W, 2W, and 3W groups. PGE2 decreased vascular perfusion pressure of the isolated stomach in the control and 2W groups, but not in the 3W group. The response of gastric vessels to PGE2 was poor in the 3W group compared with the control and 2W groups. Decreased PGE2 in the gastric mucosa and decreased response of gastric vessels to PGE2 may affect gastric blood flow in obstructive jaundice.

There is disagreement with regard to the involvement of dopamine (DA) receptors in gastric motility. The mechanisms of the inhibitory effect of DA on rat gastric motility was investigated in association with acetylcholine (Ach) release in the present study.In vivo vagotomized, splanchnicectomized rats and control rats were used, and gastric movement was determined as the gastric motility index after DA administration. In vitro study of Ach release from the circular muscle strips of the gastric corpus was investigated after administration of domperidone, SCH23390, phentolamine, or propranolol.In the in vivo study DA inhibited gastric motility in a dose-dependent manner. Vagotomy and splanchnicectomy had no effect on the inhibitory effect of DA. In vitro study DA inhibited [3H]-Ach release in a dose-dependent manner. The inhibitory effect of DA was antagonized by domperidone but not by phentolamine, propranolol, or SCH23390.Inhibition of gastric motility by dopamine is independent of extrinsic innervation and seems to be mediated by DA2 receptors in the gastric wall.

Recent studies have shown the presence of dopamine (DA) in gastric and duodenal mucosa, and changes in gastric mucosal DA content have been observed in patient with acute ulcers. Immunohistochemical demonstration of the distribution of DA in gastric mucosa under stress was studied by light and electron microscopy. In the control group, DA was present in the gastric gland proper in the gastric corpus and antrum on light microscopy, and on the surface of mucous granules in chief cells, mucous neck cells, and surface epithelium on electron microscopy. In the stress group, DA in gastric mucosa was almost undetectable on light and electron microscopy. Further, in this group serum DA concentration was significantly higher in the portal vein than in the abdominal aorta. Endogenous DA in gastric mucosal cells may affect gastric mucosa differently from exogenous DA, and stress may release endogenous intracellular DA into extracellular spaces.

The inhibitory mechanism of dopamine (DA) on rat gastric motility was investigated in association with DA receptors. Gastric movement was assessed according to the method of Jacoby et al and was expressed with the system of Ludwick et al. (1968). DA inhibited gastric movement in both the corpus and antrum in a dose-dependent manner. Domperidone, a specific antagonist of DA2 receptor, suppressed DA-induced inhibition of gastric movement in a dose-dependent manner. SCH23390, a specific antagonist of DA1 receptor did not affect DA-induced inhibition of gastric movement. LY171555, a specific agonist of DA2 receptor, inhibited gastric movement in both the corpus and antrum in a dose-dependent manner. SKF38393, a specific agonist of DA1 receptor, did not affect gastric movement. These results indicate that DA plays an important role in the inhibitory regulation of gastric motility, through DA2 receptor but not DA1 receptor.

出血性胃十二指腸潰瘍75例の治療成績から予後に影響を及ぼす背景因子について検討を加えた. 潰瘍入院総数に対する出血率は22.4%で, 手術の内訳は緊急32例, 待期27例で, 死亡率は緊急21.9%, 待期3.7%と緊急の予後が著しく悪かった. また加齢につれて死亡率は上昇し70歳以上の高齢者では19例中6例 (31.6%) であった. 予後に影響を及ぼす重要な背景因子は年齢と併存症で, シメチジン出現以後, 年度別の出血例は減少したが, 入院数に占める出血率には変化なく, 緊急手術率は前期に比べて増加した.従って, 併存症を有する高齢者に対しては保存治療に固執することなく手術適応を考慮して手術時期を失しないよう迅速に対処することが必要である.

We experimentally studied the influence of vagotomy on hepatic regeneration in rats after hepatectomy of cirrhotic livers. In animals that underwent hepatectomy plus vagotomy the reduction in gastric pH was suppressed, but gastric mucosal blood flow was less than that in control animals that received hepatectomy alone. The suppression of 3H-thymidine uptake percentage and thymidine kinase activity after hepatectomy was more marked in animals treated with hepatectomy plus vagotomy than in controls treated with hepatectomy alone. Hepatic DNA level tended to be lower in animals treated with hepatectomy plus vagotomy than in controls. In animals treated with hepatectomy plus vagotomy, the peak level of the mitotic index was lower and the hepatic regeneration rate was evidently suppressed. These results suggest that it is not appropriate to apply vagotomy, during hepatectomy of cirrhotic livers, for the prevention of postoperative stress ulcer because it causes a marked reduction in gastric mucosal blood flow and suppresses hepatic regeneration.

Changes of noradrenaline (NA) and prostaglandin (PG) E2 in gastric mucosa and gastric wall blood flow (GWBF) were investigated after stress load in rats with obstructive jaundice. We found that water immersion and restraint stress more easily increased the ulcer index and decreased GWBF, corresponding to a decrease of the NA and PGE2 contents in the gastric mucosa, as the duration of jaundice increased. Administration of PGE2 reduced the increase of the ulcer index and the decrease of the GWBF and NA contents in the gastric mucosa. It is suspected that the rapid decrease of NA and PGE2 is connected with the rapid decrease of GWBF after stress load in obstructive jaundice, and we reached the hypothesis that both PGE2 and NA mutually regulate local GWBF.

Until now, 21 cases of Crohn's disease (78% of total cases of this disease) have been surgically treated at our department. Of thse cases, 14 received a curative surgery (complete resection of the lesion). We analyzed postoperative relapes of the disease in these 14 cases. Postoperative relapse was seen in 2 (50%) of the 4 patients with Crohn's disease of the small bowel and 3 (33%) of the 9 patients with Crohn's disease of the small and large bowels. Of these 5 cases of postoperative relapse, 4 had relapse at a site close to the anastomoses. The mean timespan from the surgery to the relapse was 3 years and 3 months in patients with Crohn's disease of the small bowel and 11 months in those with Crohn's disease of the small and large bowels. The relapse rate was 13% for the patients with a preoperative IOIBD (International Organization for the Study of Inflammatory Bowel Disease) score of 4 or less and 67% for those with a preoperative IOIBD score of 5 or more. Of the 9 cases in whom the unaffected intestine was resected for 10 cm more proximal (adoral) from the lesion, no one showed postoperative relaps. Of the 5 cases in whom the unaffected intestine was reseacted for less than 10 cm proximal from the lesion, all showed postoperative relapse. However, no correlation was found between the relapse rate and the length of the resected unaffected intestine distal (towards the anus) from the lesion. Reoperation was done in 2 cases because of fistulation.

This paper describes upper gastrointestinal hemorrhage after surgical treatment of primary colorectal cancer. During the past six years, operations have been carried out on 127 patients with primary colorectal cancer. Of these, 13 patients (10%) had postoperative bleeding from the upper gastrointestinal tract. This type of bleeding occurred in 5 (26%) of 19 patients undergoing urgent surgery. With regard to the operation methods, low anterior resection and colostomy frequently induced postoperative hemorrhage, in 3 of 11 cases (27%) and 4 of 15 cases (27%) respectively; however, abdomioperineal rectal amputation did not give rise to such bleeding in any of 23 cases. Gastrointestinal hemorrhage was also noted in 4 of 11 patients having diabetes mellitus as a preoperative complication; 2 of the 4 died. This arouses prognostic concern.Of the 13 cases with postoperative gastrointestinal hemorrhage, 10 were relieved with conservative hemostasis.Therefore, prophylactic administration of Cimetidine seems to be effective in the high-risk group for postoperative gastrointestinal hemorrhage.

Changes in gastric mucosal blood flow were investigated for their relationship to gastric mucosal prostaglandin E2 (PGE2) and noradrenaline (NA) in rats with hemorrhagic shock. The results were as follows: 1) Gastric mucosal blood flow and NA decreased after hemorrhage. Gastric mucosal PGE2 initially increased after exsanguination and then markedly decreased. 2) Administration of NA before hemorrhage resulted in an increase of PGE2. However, the PGE2 value for animals receiving NA after hemorrhage was not different from that of non-NA-treated group. 3) Pre-treatment with PGE2 suppressed the reduction in both gastric mucosal blood flow and NA and the development of ulcer. These results suggest that the increase in gastric mucosal PGE2 in the early stage of shock might represent a phenomenon of adaptation by the adrenergic activation, and the decrease in PGE2 in the late stage might result from impaired synthesis of PGE2 due to persistent hypoxia and might be one of the possible factors in ulcer formation.

慢性膵炎手術46例を対象として, 膵内外分泌能と酸分泌能を対比し, さらに潰瘍成因について防御因子の面より粘膜ウロン酸を測定した. 潰瘍合併率は30.6%と高率であったが, MAOは正酸から低酸を示すのがほとんどで, 潰瘍合併例のMAOは非合併例よりも低値を示す症例が多かった. P-S試験, OGTT insulinogenic indexを指標として, 膵内外分泌障害の程度とMAO, ガストリンを比較したが相関はなかった. 胃粘膜ウロン酸量は胃潰瘍例と似た値を示し, 防御能の低下が示唆された. 潰瘍合併例に対する術式は潰瘍を含む胃切除を基本とし, 迷切術の併用は胃防御能を低下することから好ましくないと思われた.

The causes of upper digestive tract bleeding after hepatic abscission were analyzed in this study by dividing subjects into 2 groups (cirrhosis and cirrhosis-free) and taking liver function, blood coagulation surgical stress, and the kinetics of gastric acid secretion into account. The results were as follows. Upper digestive tract bleeding occured in 1 case of 15 (6.7%) in the cirrhosis-free group and in 5 cases of 19 (26.3%) in the cirrhosis group. One case was fatal. Postoperative upper digestive tract bleeding was found to have no clear relationship to the extent of the hepatic abscission or to the volume of bleeding during surgery. When compared with the cirrhosis-free controls patients with cirrhosis showed significantly worse values of GPT, TTT, ICGK, ΔIRI/ΔBS, IRI max, and hepaplastin. In the cirrhosis group the preoperative MAO value was ortho-acid (5_??_20 mEq/h) in 10 cases and hypo-acid (below 5 mEq/h) in 8 cases. All of the 5 cases which developed bleeding after surgery were in the orthoacid condition. These results indicate that patients showing a preoperative MAO value of over 5 mEq/h need to be given cimetidine positively, starting immediately after surgery.

1973年より1984年6月末までに当教室へ入院した肝硬変201例中42例 (20.9%) に潰瘍合併を認めた. 潰瘍合併群の胃酸分泌は非合併群よりも有意な差を認めないものの高い傾向を示した. しかしグリシン負荷によるガストリン値, セクレチン値には非合併群と差はなかった. 食道胃静脈瘤陽性群の潰瘍合併率は26.7%と静脈瘤陰性群の14.6%よりも高率で, しかも静脈瘤のgradeの悪化に従って潰瘍合併率は上昇した. また静脈瘤の有無およびその程度と胃酸分泌, ガストリン値, セクレチン値には差を認めなかった.

The administration of peptide YY (PYY: 0.8, 1.6 and 3.2 nmol/kg/h, i.v.) to fasting rats inhibited not only baclofen (2 mg/kg, s.c.)-stimulated gastric acid output and gastric mucosal blood flow, but also pentagastrin (8 micrograms/kg/h, i.v.)-stimulated gastric acid output. PYY (3.2 nmol/kg/h) reduced baclofen-induced acid output more than pentagastrin-induced acid output, i.e., by 61.8 +/- 11.5% compared to 35.3 +/- 8.2%. PYY inhibited acetylcholine (ACh) release from cholinergic nerve endings of gastric body evoked by electrical transmural stimulation (ETS: 1 msec, 10 V, 3 Hz, 30 sec) by 47.2 +/- 3.5%. The mechanism of the inhibitory effect of PYY on gastric acid output seems to involve decreased gastric mucosal blood flow and reduced ACh release from cholinergic nerves.