Nobuaki Wada

Alanyl-glutamine-supplemented total parenteral nutrition improves survival and protein metabolism in rat protracted bacterial peritonitis model

BACKGROUND The effects of glutamine-enriched total parenteral nutrition (TPN) solution on survival, and protein turnover in the whole body and in individual organs were investigated in a rat protracted peritonitis model. METHODS Twenty-three rats underwent venous catheter insertion. Osmotic pumps were implanted in the peritoneal cavity to allow continuous delivery of Escherichia coli (4 x 10(8) CFU/d). The conventional TPN group received a conventional amino acid solution. The Ala-Gln TPN group received an alanyl-glutamine-enriched TPN solution. The two TPN solutions were isocaloric and isonitrogenous. RESULTS Over the 5 days of TPN treatment, the survival rate of the Ala-Gln group was significantly higher than that of the conventional group. The Ala-Gln group tended to have increased whole-body protein turnover compared with the conventional group. Fractional protein synthetic rates (FSR) in the liver and gastrocnemius muscle of the Ala-Gln group were significantly higher than those of the conventional group. The serum glutamine concentration correlated positively with the FSR of both liver and muscle. The Ala-Gln group showed significantly greater mucosal height and mitoses per crypt, in the small intestine, than did the conventional group. CONCLUSIONS Our results suggested that, in comparison with standard glutamine-free TPN, Ala-Gln-supplemented TPN increases protein synthesis in the liver and skeletal muscle, protects the morphology of the intestinal mucosa, and improves survival in protracted bacterial peritonitis. Ala-Gln supplementation may be useful in septic patients.

Effect of oral administration of protease inhibitor on pancreatic exocrine function in WBN/Kob rats with chronic pancreatitis.

The effect of oral administration of protease inhibitor (camostat) on pancreatic morphology and exocrine function (conscious rat model) was investigated using WBN/Kob rats with spontaneous chronic pancreatitis. In nontreated WBN/Kob rats (2–12 months of age), pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis appeared at 3 months and advanced with each month. Pancreatic secretion was markedly impaired at all ages. In WBN/Kob rats fed diets containing camostat (from 2–3 or 4–5 months of age), the pancreas was hypertrophic and did not show any histological appearances compatible with chronic pancreatitis, and moreover, exocrine function was thoroughly restored with increased plasma cholecystokinin concentrations. Oral administration of protease inhibitor has both preventive and therapeutic effects on pancreatic lesions and dysfunction in an animal model of chronic pancreatitis, probably via endogenous cholecystokinin release.

EXPRESSION OF P21/WAF-1, STATUS OF APOPTOSIS AND P53 MUTATION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA WITH HPV INFECTION

Human papilloma virus (HPV) is regarded as a causative carcinogenic agent in anogenital squamous cell carcinoma (SCC), but there is controversy about its etiologic role in esophageal SCC (ESCC). In this study, we attempted to clarify whether HPV infection plays a crucial role in the development of ESCC by analysis of multiple factors. These included: detection of HPV DNA; evaluation of immunohistochemical assays for HPV‐related cell cycle regulators and apoptosis by the terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling method; and genetic analysis of the p53 gene. Twenty of the 48 ESCC examined (42%) were found to be positive for the HPV genome by polymerase chain reaction. They comprised 16 cases with the HPV16 subtype, three with the HPV18 subtype, and one with both HPV16 and 18. Immunohistochemical analysis revealed that the expression of p21/WAF‐1 was significantly decreased in HPV‐positive cases (χ2 = 9.2614; P = 0.0023). Furthermore, the 10 apoptosis‐negative (≤10%) cases of HPV‐positive SCC were almost exclusively p21/WAF‐1‐negative (χ2 = 12.1406; P = 0.0005), indicating the significance of the relationship between HPV infection and the phenotype that is expected from HPV‐induced inhibition of p53. Although 14 cases possessed missense and deletion mutations of the p53 gene (of which four mutations were found in HPV‐positive ESCC), no accumulation of the mutation was defined in the phenotype, suggesting that distinct mutation processes might be involved in HPV‐negative and ‐positive ESCC. The data provide significant support for the hypothesis that HPV infection may play a crucial role in the oncogenesis of some ESCC.

Effect of oral protease inhibitor administration on gallbladder motility in patients with mild chronic pancreatitis.

Oral administration of a protease inhibitor (camostat) induces pancreatic hypersecretion via hormonal and neural systems in humans. Camostat may also affect gallbladder motility via these systems. The aim of this study was to evaluate the effect of camostat on gallbladder function. Gallbladder emptying in response to caerulein administration and to egg yolk ingestion was examined ultrasonographically in 15 patients with mild chronic pancreatitis before and after 6 months of camostat treatment, and in 10 control subjects. The plasma cholecystokinin concentration after yolk ingestion was measured by radioimmunoassay. Fasting gallbladder volume and contractile function, whether stimulated by caerulein or yolk, did not differ between pancreatitis patients before camostat treatment and controls. Plasma cholecystokinin levels, basal and yolk-stimulated, did not differ between nontreated pancreatitis patients and control subjects. Fasting volume had decreased significantly by 1, 3, and 6 months of camostat treatment, while contractile function was not affected. Camostat did not influence plasma cholecystokinin levels. Oral administration of a protease inhibitor appears to decrease fasting gallbladder volume via a mechanism other than cholecystokinin release.

Tuberculous Peritonitis Defying Diagnosis : Report of a Case

A case of tuberculous peritonitis, which has beenscarcely encountered in clinical practice in recent years, is reported. A 32-year-old man was admitted to our hospital complaining of abdominal fullness, anorexia, and a 15kg weight loss. His abdomen was distended. There was neither any previous history nor recent contact with tuberculosis. The laboratory data indicated increased C-reactive protein and erythrocyte sedimentation rate, but the white blood cell count was normal. A chest X-ray examination revealed no abnormalities. abdominal X-ray showed scattered, small-intestinal gas shadows. Abdominal computed tomography scanning revealed a diffuse thickening of the dilated bowel wall, mainly adjacent to the mesentery. After a detailed examination a diagnosis of peritonitis carcinomatosa of unknown origin was suspected, and an exploratory laparotomy was done. Severe adhesions between the parietal peritoneum and the bowel were found. An excisional biopsy specimen was taken from the peritoneum, and a diagnosis of tuberculosis was thus made. Triple therapy with isoniazid, rifampicin, and kanamycin was started, and both the intestinal obstruction and anorexia were thus resolved.

Alanylglutamine-enriched total parenteral nutrition improves protein metabolism more than branched chain amino acid-enriched total parenteral nutrition in protracted peritonitis

Branched chain amino acids (BCAAs) and glutamine are both recommended in catabolic states. The object of this study was to compare the efficacies of alanylglutamine (Ala-Gln)-enriched and BCAA-enriched total parenteral nutrition (TPN) on the protein kinetics in peritonitis. Rats were divided into Ala-Gln and BCAA groups after intraperitoneal implantation of an osmotic pump, delivering a continuous infusion of Escherichia coli. Glutamine composed 30.0% (w/v) of the total amino acids in the Ala-Gln group, and BCAA composed 30.5% (w/v) of the total amino acids in the BCAA group. The two solutions were isocaloric and isonitrogenous. Whole body protein turnover and organ fractional protein synthetic rates (FSR) were measured on days 3 and 5. Serum amino acid levels and mucosal morphology were determined. Ala-Gln group had higher rates of whole body protein turnover, and hepatic FSR on both days. Serum glutamine levels correlated with hepatic and muscle FSR. Ala-Gln TPN group had greater mucosal thickness, numbers of mitoses per crypt, and FSR in distal intestine. Ala-Gln-enriched TPN may be a useful nutritional treatment modality in sepsis.

Pancreatic exocrine function during acute exacerbation in WBN/Kob rats with spontaneous chronic pancreatitis

SummaryConclusionPancreatic exocrine hypofunction is markedly deteriorated during acute exacerbation in a rat model with chronic pancreatitis.BackgroundLittle is known about pancreatic exocrine function during acute exacerbation in patients with chronic pancreatitis. We investigated changes in pancreatic exocrine function after inducing acute pancreatitis in an animal model of spontaneous chronic pancreatitis.MethodsWBN/Kob rats with chronic pancreatitis sequentially underwent pancreatic exocrine function test 1–6 d after surgical preparation with external pancreatic fistula. We induced acute pancreatitis in another WBN/Kob rats by iv administration of cerulein at a rate of 10 μg/kg/h for 4 h 4 after surgical preparation. Pancreatic exocrine function test was undertaken in a conscious state 1 d before and after cerulein administration.ResultsIn WBN/Kob rats not given cerulein, pancreatic exocrine function remained almost constant, at 3–6 d after surgery. Marked hyperamylasemia developed immediately after cerulein administration. After its administration, the pancreas microscopcially showed prominent intersitial edema and intracellular vacuolization of acinar cells in addition to the finding of pre-existing chronic pancreatitis. Basal and chole-cystokinin-stimulated flow rate, bicarbonate output, and protein output, which were substantially impaired 1 d before cerulein administration, were further reduced 1 d after its administration.

Mirizzi syndrome successfully treated by extracorporeal shock wave lithotripsy following endoscopic sphincterotomy

patients and review of the literature. Medicine 1990;69:33244. 7. Rossi RL, Heiss FW, Brassch JW. Surgical management of chronic pancreatitis. Surg Clin North Am 1985;65:79-101. 8. Duchmann JC. Endoscopic treatment of pancreaticopleural fistula. A case report. Gastroenterol Clin Biol 1995;19:837-40. 9. Kill J, Renning H. Pancreatic fistula cured by an endoprosthesis in the pancreatic duct. Br J Surg 1993;80:1316-7. 10. Saeed ZA. Endoscopic stent placement for internal and external pancreatic fistulas. Gastroenterology 1993;105:1213-7. 11. Mortensen J, Kruse A. Endoscopic management of postoperative bile leaks. Br J Surg 1992;79:1339-41. 12. Binmoeller KF. Endoscopic management of postoperative biliary leaks: review of 77 cases and report of 2 cases with biloma formation. Am J Gastroenterol 1991;86:22%31. 13. Kozarek RA. Pancreatic stents induce ductal changes consistent with chronic pancreatitis. Gastrointest Endosc 1990;36:93-5.

Gastric carcinoma presenting with extensive extraluminal growth: Report of a case

We report a 48-year-old-man with gastric carcinoma presenting with an unusual extraluminal growth. The patient underwent a barium meal examination and gastrofiberscopy because of progressive anemia over 6 months. These examinations revealed a Borrmann type 3 advanced gastric carcinoma of the greater curvature of the antrum. Biopsies showed moderately differentiated tubular adenocarcinoma. The intraoperative findings showed gastric carcinoma associated with extensive extraluminal invasion into the adjacent organs, i.e., the transverse colon and mesocolon. A palliative distal gastrectomy with a partial resection of the transverse colon was performed because of peritoneal dissemination found in the mesocolon and rectovesical pouch. A histological examination of the specimen confirmed adenocarcinoma which had massively infiltrated the transverse colon and mesocolon. His postoperative course was uneventful. However, he died of peritonitis carcinomatosa 9 months later.