Sucralfate (1.0g) was orally given each to five healthy males 2 hours after meal and its effects on the blood concentration of oral ranitidine (150mg) was investigated. When sucralfate was given together with ranitidine, the blood concentration of ranitidine was decreased compared to that after postprandial administration of ranitidine alone, and the area under the plasma concentration curve (AUC0→∞) was significantly decreased (ca. 22%) as well, suggesting the inhibitory action of sucralfate against ranitidine absorption. However, when sucralfate was given 2 hours after postprandial ranitidine administration, such effect of sucralfate was not observed at all. Therefore, in the combined oral therapy of ranitidine with sucralfate, it is theoretically desirable to separate the administration of these drugs with an adequate dosing interval.
The in vitro release of pepsinogen in bullfrogs was studied using our new system of four matched chambers. The lower esophageal mucosa of this species has been characterized to have special peptic glands without acid-secreting cells. The excised mucosa was placed in the fourth chamber which preserves the mucosal polarity with an exposed surface area of 1cm2/segment. Histamine, an acid secretagogue, demonstrated no effect on pepsinogen secretion, which was stimulated moderately by pentagastrin and strongly by bethanechol (Bch). Bch concentrations of 0.5 to 50μM were found in our system to result in concentration-dependent stimulation of pepsinogen secretion (Km 1.79μM, Vmax 30.62μg/mg•protein/hr). Atropine sulfate antagonistically inhibited the Bch-stimulated secretion of pepsinogen (pA2 9.30). Isobutylmethylxanthine, an inhibitor of the phosphodiesterase activity, and db-cAMP released pepsinogen significantly. The release of pepsinogen occurred in the presence of various concentrations of extracellular Ca2+. The pepsinogen release was reduced especially in the medium containing EGTA or containing no Ca2+. The reduction of pepsinogen release also occurred by Bch stimulation. CCCP, an inhibitor of tissue respiration, significantly inhibited the Bch-stimulated pepsinogen secretion. The cholinergic drug, Bch, induced strongest stimulation of pepsinogen secretion from the esophageal mucosa, and cAMP and Ca2+ were presumed to be associated with the process of pepsinogen release. It was concluded that the in vitro chamber system developed by us is advantageous for observation purely and singly of pepsinogen secretion without being subjected to the effect of acid secretion.
The diagnosis of Mallory-Weiss syndrome has been made with greater frequency in recent years since endoscopy of the upper gastrointestinal (GI) tract has been performed routinely on patients with upper GI tract bleeding. As a consequence, perspectives on the natural history and optimal treatments have changed considerably. In a 13-year period, we examined 2, 998 patients with acute GI tract bleeding. The Mallory-Weiss tear was the primary source of bleeding in 310 (10.3%) of these. The series included 66 females with a mean age of 43 years (range, 22-78), and 244 males with a mean age of 39.8 years (range, 13-86). Most patients (87%) gave a history of violent vomiting, retching, or gagging, suggesting the Mallory-weiss lesion. Of the tears, 61% were located at the gastroesophageal junction and averaged about 2cm in length. Eightenn percent of the patients had multiple tears. Concomitiant endoscopic findings included gastritis (70%), hiatal hernia (13%), duodenitis (15.2%), esophagitis (11%) esophageal varices (8%), and ulcer disease (7%). Overall, 90% of patients were managed supportively by observation and blood replacement; 33% required transfusions averaging 7.2 units of blood (range, 2-26 units) of those transfused, 30% received more than 6 units of blood. Other modes of mangement included endoscopic electrocoagulation (3.8%), Blakemore tube compression (1.6%), and surgery 33%). Overall mortality was 3.9%, and all deaths were related to severe cirrhosis of aspiration pneumonitis. Prolapse of the gastric mucosa into the esophagus during retching was observed in 19 patients during endoscopy. This is believed to be an important etiologic factor in patients with the Mallory-Weiss syndrome.
A study was made on the diagnosis of the depth of cancerous invasion by means of endoscopic ultrasonography (EUS). In 81 gastric cancers of resected stomach, ultrasonographic appearance of the deepest layer in the cancerous invasion was noticed. Ultrasonographic pattern of the third layer was classified into three groups (Type I, II, III) and ultrasonographic pattern of the fourth layer into two groups (Type A, B). In the protruded type and IIa+IIc type of early gastric cancer, cancerous tissue in all cases of Type I limited in the mucosa, and in all cases of Type III invaded into the submucosa. In the depressive type of early gastric cancer, cancerous tissue in 67% of cases in Type I limited in the mucosa, in 64% of cases in Type II showed the submucosal invasion, in all cases of Type III invaded into the submucosa. The ultrasonographic findings of Type B of advanced gastric cancer signified scirrhous cancerous invasion. EUS were performed in 35 patients clinically. The degree of cancerous invasion was able to be diagnosed with EUS more aculately than with X-ray and endoscopic examination. Extraserosal invasion was diagnosed only by EUS.
To investigate the significance of neutralization of acid in the duodenaum, the proximal duodenal loop of rats, excluding the bile duct opening, was perfused with acidic saline, and the amount of alkali secreted by the loop was determined by continuous titration using pH-stat. The influence of cysteamine and secretin on the alkaline secretion was studied. It was found that the proximal duodenal mucosa of rats secretes bicarbonate enough to neutralize the incoming acid. A significant inhibition of the alkaline secretion by cysteamine, in a dose enough to induce perforating duodenal ulcers, and a significant reversal of the cysteamine-induced inhibition of the alkaline secretion were also found. From the above findings, the possible participation of the impaired alkaline secretion to the formation of duodenal ulcers and the therapeutic role of secretin to improve the alkaline secretion were indicated.
Aminopeptidase activities in brush border membrane fractions were significantly higher in the group on a small peptides elemental diet (SP-ED) than in the group on an amino acids elemental diet (AA-ED). In those on SP-ED, aminopeptidase activities showed an enzymic gradient along the villus crypt axis with time and became completely distributed in the villus. The elevation of activities was inhibited by cycloheximide and was a reversible response. In this way we made it clear that brush border aminopeptidase was one of the adaptation enzymes induced by oligopeptides as intraluminal substrates. Cytosol dipeptidase activities were also higher in the group on SP-ED than in those on AA-ED, and the former showed increases in the absorption of dipeptide (glycyl-L-leucine) and amino acids (glycine, L-leucine) in vitro experiment on the small intestine.
Rabbits were skin sensitized by E. coli lipopolysaccharide (LPS) and challenged with an intrarectal instillation of LPS (6mg/20ml) after a 1% formalin enema (20ml). Ulcers and bleeding appeared on the 3rd day and mild macroscopic changes continued for about 2 weeks. By repeating the LPS enema (2 times/wk) after 7 days, the colitis maintained for over one month. When sensitization was performed by bolied E. coli present in their own feces, mucosal inflammations including cryptabscesses appeared only by 1% formalin enema, and they lasted for 40 days. Tissue fibrinolysis of large intestines showed a significant increase as the mucosal damage appeared.
To investigate insulin-like growth factor-I (IGF-I) in patients with acute hepatitis, we measured the serum levels of IGF-I using radioimmunoassay. Serum levels of IGF-I in normal controls and patients with acute hepatitis and fulminant hepatitis were 257±67, 158±78 and 69±61fmol/ml, respectively (p<0.005). IGF-I levels were significantly correlated with the values of hepaplastin test. These findings suggested that IGF-I levels reflected the severity of the diseases and hepatic reserve in acute hepatitis. Furthermore, it was appeared that IGF-I level in recovery phase of fulminant hepatitis was increased, and this finding indicated that IGF-I might be correlated with liver regeneration in acute hepatitis.
Elective and prophylactic EIS was performed in 67 cirrhotic patients with esophageal varices. Portographic studies were made before and after EIS on the collateral hemodynamics of the portal system. Studies were also made on the liver function and on the cause of death after EIS. In 18 out of 34 cases, PVP was decreased in a few months after EIS and the reformation of collateral directional flow pattern was found in 13 cases of those 18. The rest of them showed increased PVP after EIS. However there was no influence of PVP changes on the liver function in both groups. It was suggested that EIS provoke the similar collateral changes as was reported by Idenzuki, who described same changes after transthoracic esophageal transection (Walker 1952). Studies on cause of death in 11 cases after EIS revealed that the association of hepatocellular carcinoma and/or portal thrombosis was an important factor in prognosis even though complete eradication of esophageal varices was accomplished by EIS.