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Biomedical subjects

E P Dimagno

Publications and source records attributed to E P Dimagno.

17 recordsLinked to original sources

Cigarette smoking accelerates progression of alcoholic chronic pancreatitis.

BACKGROUND: Smoking is a recognised risk factor for pancreatic cancer and has been associated with chronic pancreatitis and also with type II diabetes. AIMS: The aim of this study was to investigate the effect of tobacco on the age of diagnosis of pancreatitis and progression of disease, as measured by the appearance of calcification and diabetes. PATIENTS: We used data from a retrospective cohort of 934 patients with chronic alcoholic pancreatitis where information on smoking was available, who were diagnosed and followed in clinical centres in five countries. METHODS: We compared age at diagnosis of pancreatitis in smokers versus non-smokers, and used the Cox proportional hazards model to evaluate the effects of tobacco on the development of calcification and diabetes, after adjustment for age, sex, centre, and alcohol consumption. RESULTS: The diagnosis of pancreatitis was made, on average, 4.7 years earlier in smokers than in non-smokers (p = 0.001). Tobacco smoking increased significantly the risk of pancreatic calcifications (hazard ratio (HR) 4.9 (95% confidence interval (CI) 2.3-10.5) for smokers v non-smokers) and to a lesser extent the risk of diabetes (HR 2.3 (95% CI 1.2-4.2)) during the course of pancreatitis. CONCLUSIONS: In this study, tobacco smoking was associated with earlier diagnosis of chronic alcoholic pancreatitis and with the appearance of calcifications and diabetes, independent of alcohol consumption.

Adult↗

Neural network analysis of EUS images to differentiate between pancreatic malignancy and pancreatitis.

BACKGROUND: The differentiation of focal pancreatitis and pancreatic adenocarcinoma is problematic and often resolved only by pancreaticoduodenectomy. EUS is the most sensitive imaging modality for both conditions, yet ultrasonic criteria for distinguishing the two have not been described and differentiation remains difficult. The aims of this study were to develop a self-learning computer program that can analyze EUS images and differentiate malignancy from pancreatitis, and to compare results obtained with this system with EUS interpretation by experienced endosonographers. METHODS: Twenty-one patients with pancreatic cancer and 14 with focal pancreatitis were included. The diagnosis was confirmed histologically in all cases and each patient had undergone EUS. A single EUS image from each procedure was used for computer analysis. The results were compared with the EUS diagnosis reported at the actual procedure as well that of an endosonographer who reviewed videotapes of the procedures. RESULTS: The software program differentiated focal pancreatitis from malignancy with a maximal 89% accuracy. With sensitivity set at 100% for malignancy, the program was 50% specific and accuracy was 80%. Sensitivity and accuracy of the endosonographer's impression at the time of EUS were, respectively, 89% and 85%. A sensitivity of 73% and accuracy of 83% were achieved with blinded interpretation of EUS videotapes. CONCLUSIONS: Analysis of EUS images with computer software programs is feasible and compares favorably with human interpretation. The application of this technology to EUS and other imaging scenarios could be a useful adjunct to diagnostic endoscopy and warrants further investigation.

Adenocarcinoma↗

Effect of prolonged intraluminal alpha-amylase inhibition on eating, weight, and the small intestine of rats.

Effects of chronic intraluminal amylase inhibition on eating and the digestive system are unclear. In growing rats, we determined the effect of ingesting a wheat amylase inhibitor (AI) on eating, weight, small intestinal mucosal growth, and disaccharidases. Three groups of 12 rats received AI, were pair-fed controls (PFC), or had free access to food (FAC). After measuring food intake and body and stool weight for 21 d, rats were decapitated and the small intestine was divided into four segments. AI and PFC rats had similar food intake, weight gain, and stool output, but these were less than FAC rats (P < 0.005). AI rats ate less (P < 0.001) than PFC during the light cycle and less than FAC rats during darkness. Mucosal DNA and RNA were reduced (P < 0.05) in the upper small intestine of AI and PFC rats compared with FAC rats. Mucosal weight, RNA, and disaccharidase activities were greater (P < 0.01) in the ileum of AI rats compared with PFC and FAC rats. AI alters the amount and pattern of food intake, reduces weight gain, upper small intestinal mucosal weight, protein and DNA, and increases distal small intestinal mucosal weight, RNA, and disaccharidases. AI likely causes these effects by inducing satiety and increasing carbohydrate delivery to the distal intestine.

Animals↗

Chronic pancreatitis.

In the past year, numerous important papers were published on chronic pancreatitis, its causes, and its diagnosis; the cause of fibrosis; and pain in pancreatic cancer. More than 750 mutations have been described in the cystic fibrosis transmembrane regulator (CFTR) gene. Some mutations cause relatively mild reductions in CFTR function and may lead to disease in one organ without clinical involvement of other organs. Two groups of investigators recently reported that "idiopathic" chronic pancreatitis may be the sole manifestation of some CFTR mutations. Some recent reports may enhance our understanding of pancreatic fibrogenesis and may lead to therapies for painful chronic pancreatitis. Pancreatic stellate cells are vitamin A-containing cells that resemble hepatic stellate cells and were recently isolated from rat and human pancreas. They respond to inflammatory cytokines by producing collagen. Two studies show that endoscopic ultrasonography (EUS) correlates well with endoscopic retrograde cholangiopancreatography in moderate to severe chronic pancreatitis. However, in patients who have a few nondiagnostic abnormalities on EUS, these results have poor correlation with the results of endoscopic retrograde cholangiopancreatography and the secretin test. The clinical significance of these abnormalities is unclear, and the diagnosis of chronic pancreatitis should not be based on EUS findings alone. Painful chronic pancreatitis is a complex and difficult management problem. A recent study of alcoholic chronic pancreatitis suggests that the best predictors of pain relief are an intermittent pattern of pain and the presence of surgically correctable complications (eg, pseudocysts or biliary obstruction). An American Gastroenterological Association technical review of painful chronic pancreatitis emphasized the lack of controlled studies supporting any form of therapy. Further evidence that longstanding chronic pancreatitis is a premalignant condition has been provided by recent epidemiologic, pathologic, and molecular biology studies.

Journal Article↗

Is the plasma amino acid consumption test an accurate test of exocrine pancreatic insufficiency?

BACKGROUND/AIMS: The amino acid consumption test has been proposed as an accurate test of exocrine pancreatic function. The diagnostic accuracy of this test was determined by simultaneously measuring plasma amino acids and enzyme secretion during stimulation of the pancreas with cholecystokinin octapeptide (CCK-OP) in 60 consecutive patients suspected of having pancreatic insufficiency. METHODS: All patients underwent duodenal intubation and intravenous infusion of CCK-OP (40 ng.kg-1.h-1). Pancreatic enzyme (lipase and trypsin) outputs and plasma amino acids were measured for a period of 1 hour. Total and individual plasma amino acids were quantitated by ion-exchange chromatography. The severity of pancreatic insufficiency was graded on the basis of enzyme output during CCK-OP infusion. RESULTS: There was no relationship between pancreatic enzyme output and plasma concentrations of individual or total amino acids before or during CCK-OP stimulation. Using a total amino acid decrease of 12% as the cutoff, the amino acid consumption test was 91% sensitive, but very nonspecific (21% specificity) for detection of pancreatic insufficiency. CONCLUSIONS: The amino acid consumption test with CCK-OP stimulation does not discriminate between patients with normal and impaired exocrine pancreatic secretion.

Adult↗

Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group.

BACKGROUND: The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases. METHODS AND RESULTS: We undertook a multicenter historical cohort study of 2015 subjects with chronic pancreatitis who were recruited from clinical centers in six countries. A total of 56 cancers were identified among these patients during a mean (+/-SD) follow-up of 7.4 +/- 6.2 years. The expected number of cases of cancer calculated from country-specific incidence data and adjusted for age and sex was 2.13, yielding a standardized incidence ratio (the ratio of observed to expected cases) of 26.3 (95 percent confidence interval, 19.9 to 34.2). For subjects with a minimum of two or five years of follow-up, the respective standardized incidence ratios were 16.5 (95 percent confidence interval, 11.1 to 23.7) and 14.4 (95 percent confidence interval, 8.5 to 22.8). The cumulative risk of pancreatic cancer in subjects who were followed for at least 2 years increased steadily, and 10 and 20 years after the diagnosis of pancreatitis, it was 1.8 percent (95 percent confidence interval, 1.0 to 2.6 percent) and 4.0 percent (95 percent confidence interval, 2.0 to 5.9 percent), respectively. CONCLUSIONS: The risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis and appears to be independent of sex, country, and type of pancreatitis.

Adult↗

Assessment of weight loss, food intake, fat metabolism, malabsorption, and treatment of pancreatic insufficiency in pancreatic cancer.

In 12 patients with biopsy-proven pancreatic ductal adenocarcinoma, the following were determined: (1) whether decreased food intake, malabsorption, or altered fat metabolism were associated with weight loss; (2) the effect of pancreatic extract as treatment for malabsorption; and (3) the accuracy of the triolein breath test for detection of steatorrhea. Weight loss occurred in 11 patients and only in patients who had either malabsorption (n = 5), low coefficients of caloric consumption (n = 2), or both (n = 4). Nine patients had fat malabsorption, six had protein malabsorption, and caloric consumption was decreased in seven patients. Metabolism of oleic acid was significantly decreased (P less than 0.01) compared to normal subjects and correlated with basal metabolic rates (r = 0.6; P less than 0.05) which were within the range of normal values for age and sex. Body weight loss correlated only with coefficients of fat and protein absorption (r = 0.59; P less than 0.05). Treatment of patients with pancreatic extract resulted in significant improvement in absorption in those with moderate to severe fat or protein malabsorption (coefficient of absorption less than 80%) but no significant improvement occurred in patients with mild fat or protein malabsorption. The triolein breath test was abnormal in all patients with fat malabsorption and predicted improvement of fat absorption in five of six patients with steatorrhea who were treated with pancreatic extract. Thus, in pancreatic cancer, weight loss is associated with malabsorption; exogenous pancreatic extract significantly improves moderate to severe fat or protein malabsorption, and the triolein breath test detects fat malabsorption and predicts the treatment response to pancreatic extract.

Adult↗

Human endoscopic ultrasonography.

Conventional transcutaneous ultrasound examinations are often compromised by intervening pulmonary or bowel gas and have limited resolution. Ultrasonic probes of frequencies greater than 5 MHz, which enhance resolution, cannot be used successfully on the skin surface, because they do not penetrate deeply enough to view intraabdominal organs in most adults. To overcome these problems, we tested an ultrasonic endoscope which had a 10-MHz, 64-element linear assay, generated real-time images at resolutions of less than 1 mm, and was an integral part of a 35-mm-long and 13-mm-wide endoscopic rigid tip. Thirty-two studies were performed in 15 healthy subjects, 4 patients with pancreatic cancer and 6 patients with chronic pancreatitis, and 1 patient each with a gastric ulcer and a suspected pancreatic abscess. We demonstrated that this procedure is safe, provides high resolution real-time ultrasound visualization of the heart, aorta, spleen, pancreas, liver, gallbladder, kidneys, and gastrointestinal mucosa and can detect moderate-sized pancreatic tumors and hepatic metastases less than 1 cm in diameter. Because endoscopic visualization of gastrointestinal mucosa and ultrasound examination of extraluminal organs can be obtained during a single procedure, rapid differentiation among mucosal and intramural disease of the hollow gut and disease of extraluminal organs should be possible with this diagnostic technique.

Digestive System↗

Interdigestive canine pancreatic juice composition and pancreatic reflux and pancreatic sphincter anatomy.

Canine and human exocrine pancreatic secretion into the duodenum during fasting is cyclical and related to intestinal motility. To characterize the composition of pure pancreatic juice during the cyclically recurring sequence of propagated motor events (interdigestive motor complex) and to establish whether pancreatic reflux occurs, dogs were prepared with three permanent indwelling duodenal catheters and a pancreatodochal cutaneous catheter. The duodenal catheters were used to record duodenal pressures and measure pancreatic secretion of trypsin, lipase, and bicarbonate, based on the recovery of a constantly perfused marker, [14C]PEG. Pancreatic duct pressures or pancreatic juice concentrations of [14C]PEG, trypsin, lipase, or bicarbonate (done separately in each of five dogs throughout one interdigestive cycle on 4 different days) were related to duodenal motor activity. Finally, the pancreatic duct orifice of freshly sacrificed dogs was examined by light and electron microscopy. During fasting, (1) pancreatic volume secretion increased 10-fold during phases II, III, and IV (P less than 0.001), and bicarbonate concentration increased during phases III and IV (P less than 0.05) compared with phase I, while trypsin and lipase concentrations did not change; (2) reflux of duodenally perfused [14C]PEG into the pancreatic duct occurred in two of five dogs and was minimal (less than 0.1%); and (3) a positive mean pressure gradient from duodenum to pancreatic duct occurred only during phase III (7.4 +/- 4.1 cm H2O). Anatomic studies of the pancreatic duct opening showed a specialized papillary mucosa and an independent crescentic sphincter muscle. We conclude that during fasting, pancreatic juice composition is intimately linked to the different phases of interdigestive intestinal motor activity and that an efficient antireflux mechanism exists.

Animals↗

Duodenogastric reflux in humans: its relationship to fasting antroduodenal motility and gastric, pancreatic, and biliary secretion.

Duodenogastric reflux may have pathophysiologic importance, but its mechanism is poorly understood. We propose that duodenogastric reflux and periodic changes in motor and secretory activity of the upper gut during fasting may be related. Therefore we determined the relationships between duodenogastric reflux and interdigestive motor-secretory cycles in a group of 6 healthy individuals, on each of whom we performed three 7-h studies in random order on separate days. In all studies gastric intubation and antral pressure recordings were performed. However, in design 1 we used a slow duodenal perfusion rate of [14C]PEG in saline (0.25 ml/min) while in design 3 we used a fast perfusion rate (3.0 ml/min). Duodenal pressures were also recorded during these designs. In design 2 no transpyloric tubes were present. Our study shows that, in humans, fasting duodenogastric reflux of bile and pancreatic juice is cyclic and closely related to the interdigestive migrating motor complex. Reflux is highest during late phase II (when secretory activity is also on the rise) and lowest after phase III. One of the important functions of the migrating motor complex in humans may be to clear the stomach of refluxed duodenal secretions.

Adult↗

Postprandial gastric function in pancreatic insufficiency.

Abnormalities in postprandial gastric function could contribute to the maldigestion of pancreatic insufficiency. To measure simultaneously postprandial gastric secretion and emptying and correlate these measurements with intraluminal duodenal changes, we performed intestinal intubation and duodenal perfusion during feeding of a solid-liquid test meal in 10 healthy controls and 10 patients with documented pancreatic insufficiency before and after replacement therapy. In pancreatic insufficiency, intraduodenal pH was significantly decreased late in the postprandial period while simultaneously measured duodenal acid loads were normal, confirming that reduced bicarbonate output rather than increased acid delivery was responsible for higher duodenal acidity in these patients. Significant (P less than 0.05) reductions in postprandial acid, pepsin, and total secretory outputs were noted in untreated patients only during the first postprandial hour. Absolute gastric emptying rates were lower in patients (P less than 0.05) than in healthy subjects, but fractional rates of emptying were similar. Fasting and postprandial hypergastrinaemia were consistently observed in the patients with pancreatic disease. There are postprandial disturbances of secretory function but no primary gastric motor defect in patients with exocrine pancreatic insufficiency.

Duodenum↗

Reduced intraluminal bile acid concentrations and fat maldigestion in pancreatic insufficiency: correction by treatment.

Malabsorption of bile acids is known to occur in patients with pancreatic insufficiency particularly when due to cystic fibrosis. Abnormal biliary secretion or intraluminal acidic precipitation of bile acids could contribute to the steatorrhea of pancreatic insufficiency. To measure bile acid outputs and duodenal concentrations of bile salts and lipids simultaneously, we performed intestinal intubation and perfusion studies during feeding of a solid test meal in 6 healthy controls and 8 adult patients with advanced acquired exocrine pancreatic insufficiency. The effects of various treatment regimens were also investigated. Postprandial bile acid secretion was similar in all treatment groups. However, significant (P less than 0.05) reductions in micellar concentrations of bile acids and fatty acids were observed in untreated pancreatic insufficiency. These abnormalities were directly related to pH-induced precipitation of bile acids and were corrected only by the addition of cimetidine to standard pancreatin therapy. Thus, in pancreatic insufficiency, treatment with pancreatin plus cimetidine enhances fat digestion and absorption by reducing both acid-peptic inactivation of lipase and acidic precipitation of bile acids.

Administration, Oral↗

Pancreatic insufficiency and Ménétrier's disease. Report of a case with clinical response to pancreatic enzyme replacement.

A patient with exocrine pancreatic insufficiency and hypoalbuminemic edema was shown also to have a protein-losing gastropathy secondary to giant hypertrophic gastritis (Ménétrier's disease). Despite continuation of excessive gastric protein loss, the manifestations of hypoproteinemia were reversed by oral pancreatic enzyme replacement therapy. We speculate that impaired intraluminal proteolysis exaggerated the consequences of gastric protein loss.

Gastritis↗

Rationale for the use of cimetidine in pancreatic insufficiency.

The failure of standard oral pancreatic enzyme replacement therapy to correct malabsorption in patients with advanced pancreatic insufficiency is likely due to acid-peptic inactivation of ingested enzymes. Theoretically, the use of cimetidine, an H2-receptor antagonist, in conjunction with oral enzymes, would permit greater transgastric passage of ingested enzymes with resulting improvement in intraluminal lipolysis. To test this hypothesis, we studied the effects of orally administered cimetidine in two groups of patients by utilizing a previously validated double-marker perfusion technique. Cimetidine, in varying doses, had no effect on postprandial exocrine pancreatic function in 16 duodenal ulcer patients without pancreatic disease. In six patients with pancreatic insufficiency, cimetidine produced a pronounced decrease in the output of gastric acid and secretory volume, resulting in reduction of postprandial acidity and intragastric volume. These actions of cimetidine should retard or prevent inactivation of ingested enzymes and also increase their intragastric concentration, with resulting enhancement of luminal duodenal enzyme activity. Supplemental cimetidine may thus be useful in the medical management of patients who fail to respond to routine pancreatic extract therapy alone.

Adult↗