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W H Nealon

Publications and source records attributed to W H Nealon.

30 records · Page 2Linked to original sources
PubMed1990

Proglumide inhibits cholecystokinin and meal-stimulated pancreatic secretion and release of pancreatic polypeptide.

Exogenously administered cholecystokinin is a potent stimulant of pancreatic exocrine secretion and pancreatic polypeptide release. Release of cholecystokinin by amino acids and fats is strongly correlated with both pancreatic exocrine secretion and pancreatic polypeptide release. Despite this correlation, direct evidence that cholecystokinin is a physiologic mediator of these actions is not available. We have studied this problem in fasted dogs with chronic pancreatic fistulas by means of a specific cholecystokinin antagonist, proglumide, to inhibit the effect of cholecystokinin. Secretion, neurotensin (with secretin stimulation infusion), or cholecystokinin-octapeptide was infused intravenously, either with saline solution or with proglumide (300 mg/kg/hr). For endogenous release of cholecystokinin, intraduodenal infusions of phenylalanine and tryptophan or of sodium oleate were given with either intravenous saline solution or intravenous proglumide. Pancreatic secretion and release of cholecystokinin and pancreatic polypeptide were measured in plasma. Cholecystokinin-octapeptide stimulated pancreatic secretion of water and protein; both of these were significantly inhibited by proglumide. Intraduodenal amino acids and sodium oleate both caused significant release of cholecystokinin, which was not altered by proglumide; however, proglumide inhibited pancreatic secretion stimulated by intraduodenal amino acids and sodium oleate. Release of pancreatic polypeptide stimulated by amino acid and sodium oleate was also significantly inhibited by proglumide. Since proglumide appears to block actions of cholecystokinin, our results show that cholecystokinin is physiologically important for pancreatic secretion and for release of pancreatic polypeptide.

Amino Acids↗
PubMed1989

Preoperative endoscopic retrograde cholangiopancreatography (ERCP) in patients with pancreatic pseudocyst associated with resolving acute and chronic pancreatitis.

Experience with patients with pancreatic pseudocysts has led the authors to the hypothesis that preoperative evaluation of the pancreatic and bile ducts by ERCP will define those patients who may be inadequately treated by pseudocyst drainage alone without attention to associated pancreatic and biliary ductal abnormalities. In patients with certain ductal abnormalities, the pseudocyst operation was combined with a definitive operative drainage of the pancreatic duct and/or of the biliary tree where appropriate. A prospective evaluation of routine preoperative ERCP was undertaken over a 36-month period in all patients scheduled for operative treatment of pseudocyst of the pancreas. From an initial group of 44 patients with pseudocysts, three patients who had spontaneous regression of the pseudocyst were excluded. ERCP was successful in 39 of the remaining 41 patients. Among 41 operated patients, 24 were admitted with a diagnosis of pseudocyst that arose after an episode of acute pancreatitis, and 17 had chronic pancreatitis with pseudocyst. Nine patients, initially assumed to have acute pancreatitis, were recognized to have chronic pancreatitis on the basis of ERCP findings. Communication with the main pancreatic duct (MPD) was demonstrated in 18 of 41 pseudocysts, and the rate of communication was similar in patients with acute and chronic pancreatitis. Dilatation of the MPD was seen in 23 of 41 patients and was associated with chronic pancreatitis in 21. Dilatation of the common bile duct was found in 12 patients with chronic pancreatitis. The operative plan was altered by ERCP findings in 24 of 41 patients; 22 of the 24 patients had chronic pancreatitis. There were no complications of ERCP. These data suggest that ERCP should be performed in all patients with pseudocysts to establish correct diagnosis and to allow optimal choice of operation.

Acute Disease↗
PubMed1989

Operative strategies in the management of mediastinal pancreatic pseudocyst.

Thirty-four cases of mediastinal pancreatic pseudocyst have been previously reported. Among the 32 previous reports with operative or autopsy analysis, communication has been identified in 30. Even when this communication has been quite small between the mediastinal fluid collection and the pancreas, the recommended operative strategy has been enteric drainage directly to this communicating tract. We report the case of a patient with a mediastinal pancreatic pseudocyst in whom the communication between the pancreas and the pseudocyst was not located. The condition was managed by drainage of the mediastinal pseudocyst with decompression of the main pancreatic duct by means of a longitudinal pancreaticojejunostomy in a patient with chronic pancreatitis.

Aged↗
PubMed1989

Combined endoscopic and fluoroscopic balloon dilatation of a complex proximal jejunal stricture.

Dilatation of esophageal strictures has been practiced for many years. More recently, balloon dilatation, with endoscopic guidance, has been applied to the stomach and the colon. The small bowel has been less accessible to the endoscope, and, as far as we have been able to determine, balloon dilatation of jejunal strictures has not been reported. We present a patient who was referred to us after curative resection of two abdomino-pelvic malignancies, external beam irradiation to the abdomen and pelvis, and multiple later operations for bowel obstruction and dehiscence of intestinal anastomoses. The bowel obstruction and anastomotic dehiscence occurred during the present hospitalization and resulted finally in the development of a high-output proximal jejunal fistula. The area of stricture, as seen by means of barium contrast, had two separate components with an associated acute angulation. We report the combined use of endoscopic and fluoroscopic manipulation and balloon dilatation of this complex stricture.

Aged↗
PubMed1988

Hepatobiliary abnormalities associated with total parenteral nutrition.

Hepatobiliary abnormalities occur often in patients receiving TPN. Although TPN use may be important in their pathogenesis, many other factors could also be involved. In any individual patient it may be difficult to separate the contribution of TPN itself from that of the other precipitating causes. The most worrisome observation to date is the development of severe progressive liver disease in a small number of patients receiving long-term TPN. Further work is needed to determine whether the use of TPN actually contributes to this condition or is simply an associated finding.

Cholelithiasis↗
PubMed1988

Operative drainage of the pancreatic duct delays functional impairment in patients with chronic pancreatitis. A prospective analysis.

In a prospective study, 85 patients with chronic pancreatitis have been subjected to evaluation by morphologic analysis (endoscopic retrograde cholangiopancreatography), by exocrine function tests (bentiromide PABA and 72-hour fecal fat testing), and by endocrine function tests (oral glucose tolerance test and fat-stimulated release of pancreatic polypeptide). All patients were graded on a five-point system, with 1 point assessed for an abnormal result in each of the five tests performed. Zero score denoted mild disease; 1-2 points signaled moderate disease; and 3-5 points indicated severe disease. In 68 patients, both an initial and late (mean follow-up period of 14 months) evaluation were performed. Forty-one patients underwent modified Puestow side-to-side Roux-en-Y pancreaticojejunostomy. The Puestow procedure alone was performed in 18 patients. Eight patients also had drainage of pseudocysts, seven also had a biliary bypass, and eight had pseudocyst drainage plus bypass, in addition to the Puestow. There were no deaths. Of the 68 patients who were studied twice, 30 had operations and 38 did not. None of the patients with severe disease improved their grade during follow-up. Of 24 patients who did not undergo operation, 17 (71%) who were graded mild/moderate progressed to a severe grade at follow-up. By contrast, only three of the 19 patients operated on (16%) and who were initially graded as mild/moderate progressed to severe disease at follow-up testing. More than 75% of all of the patients had a history of weight loss. Twenty-six of 30 patients operated on (87%) (all of whom had lost weight before surgery) gained a mean 4.2 kg (range 1.4-2.7 kg) after surgery, compared with no significant weight change (range -3.6-2.7 kg) among patients not operated on. These findings support a policy of early operation for chronic pancreatitis, perhaps even in the absence of disabling abdominal pain.

Adult↗
PubMed1988

The time course of beta cell dysfunction in chronic ethanol-induced pancreatitis: a prospective analysis.

Insulin-glucose homeostasis was examined in 62 patients with chronic pancreatitis (CP). All patients were graded on the basis of test results from five studies: (1) endoscopic retrograde cholangiopancreatography, (2) fat-stimulated release of pancreatic polypeptide (PP), (3) NBT-bentiromide PABA test, (4) 72-hour fecal fat test, and (5) oral glucose tolerance test (OGTT). Patients with CP were graded as either mild/moderate or severe by means of a scoring system that we devised and have previously reported. Nineteen patients were graded as mild/moderate and 43 patients were graded as severe. The endocrine function of non-beta and beta islet cells was compared by assessing release of PP after fat and by release of insulin during OGTT. Release of PP was depressed in 58%, and the depressed output was found in only patients with a severe grade of CP. Forty-four of 62 patients (71%) with CP had abnormal OGTT findings; the distribution of this abnormality was not greatly different between mild/moderate and severe grades. Depressed release of insulin was seen in 58% (36 of 62)--more commonly in patients with a severe grade (10%) but also in 32% of patients with a mild/moderate grade. A subset of patients with CP sustains early beta-cell dysfunction. We conclude that decreased output of PP is a more reliable measure of functional deficit and stage in CP.

Adult↗
PubMed1988

Establishment of a human gastrinoma in nude mice.

We report the first establishment and characterization of functioning gastrinoma from a human being transplanted into nude mice. Tissue was obtained at operation from a gastrinoma liver metastasis from a patient with the Zollinger-Ellison syndrome. The tumor was implanted subcutaneously in five athymic nude mice. Serum gastrin was measured by means of radioimmunoassay in specimens of mouse blood taken before and 5 minutes after intraperitoneal injection of secretin (100 micrograms/kg). In a second experiment serum gastrin was measured 30 minutes after injection of somatostatin analogue, SMS 201-995 (300 micrograms/kg). Studies were also done in 10 control mice. At passage, the fundus of each tumor-bearing mouse was weighed and examined microscopically. The gastrinoma (tumor line, PT) has been maintained for 34 months through four passages with a tumor doubling time of 37 to 45 days. The histology is similar to the original tumor. Immunocytochemistry showed that PT contained gastrin. In two mice metastasis developed 9 months after implantation. Gastrin levels in mice bearing PT have ranged from 216 to 12,000 pg/ml. Gastrin levels of control mice ranged from 0 to 63 pg/ml. Secretin increased gastrin levels in three of five mice tested and decreased gastrin levels in two mice. Repeat secretin tests showed identical results. SMS 201-995 decreased gastrin levels from basal values. Fundic weight of mice bearing PT (397 +/- 93 mg) was significantly greater than control fundic weight (180 +/- 26 mg). Gastrinomas growing in nude mice produce physiologically active gastrin as shown by elevated serum gastrin levels and by hyperplasia of the stomach. Two distinct subpopulations of gastrinoma cells respond differently to secretin. This model should provide important information on mechanisms of growth control and on gastrin release by gastrinomas in human beings.

Adult↗
PubMed1987

Role of cholecystokinin in canine pancreatic exocrine response to bombesin stimulation.

The role of cholecystokinin in bombesin-stimulated pancreatic secretion in dogs was examined by the use of a specific cholecystokinin antagonist, proglumide. The primary component of bombesin-stimulated pancreatic secretion at the lowest tested dose was due to cholecystokinin, with only 25 percent of bombesin-stimulated protein output preserved during proglumide infusion. Maximal stimulation of cholecystokinin release was achieved by even the lowest dose of bombesin, whereas dose-related increases in bombesin-stimulated protein secretion were observed. This increase in exocrine secretion is probably explained by increased direct bombesin stimulation. Our findings suggest that the maximal dose of bombesin is lower for cholecystokinin release than its effective dose for enzyme secretion. We conclude that, in all probability, postprandial release of bombesin (or its analogue, gastrin-releasing peptide) affects pancreatic function primarily through release of cholecystokinin.

Animals↗
PubMed1987

Correlation of cholecystokinin receptors with gallbladder contractility in patients with gallstones.

The authors have previously identified two groups of patients with gallstones: those whose gallbladders contract the same as those of normal volunteers and show an increased sensitivity to endogenous cholecystokinin (CCK) ("contractors") and those whose gallbladders are relatively unresponsive ("noncontractors"). To define the mechanism responsible for these differences in contractility, the authors have measured CCK receptors on gallbladder muscle of patients with gallstones. Twenty-three patients with gallstones and 10 healthy volunteers (controls) fasted overnight. Simultaneous plasma samples for radioimmunoassay of CCK release and ultrasonographic measurements of gallbladder volume were obtained before and at intervals for 60 minutes after ingestion of Lipomul. Patients with gallstones had cholecystectomy, and CCK receptors were determined on cell membranes from gallbladder specimens by use of radiolabeled analogs of CCK-8-SO4. Histologic sections were graded for the degree of inflammation and scarring. Thirteen patients with gallstones were identified as contractors and 10 as noncontractors. Basal gallbladder volumes were not significantly different between patients in either group. The total integrated output of CCK for contractors was 1.6 +/- 0.2 ng X min/ml compared with 5.5 +/- 1.2 ng X min/ml for controls, while the integrated output for noncontractors was 11.1 +/- 2.1 ng X min/ml. Contractors had a higher number of CCK-binding sites (27.6 +/- 6.8 fmol/mg protein) than did noncontractors (4.8 +/- 1.0 fmol/mg protein). CCK receptors in gallbladders of all patients with gallstones correlated closely with gallbladder motility (y = 1.149, x = 0.624, r = 0.7, p less than 0.001). Although contractors had more mild inflammation and scarring, 40% of noncontractors had mild inflammation and scarring; there was no correlation. A decrease in CCK receptors may be an early event in the pathogenesis of gallstone formation by causing a decrease in gallbladder motility in some patients.

Adult↗
PubMed1986

Diagnostic role of gastrointestinal hormones in patients with chronic pancreatitis.

Thirty-three patients with chronic pancreatitis were studied in an effort to correlate release of gastrointestinal hormones (GIH) with the degree of pancreatic insufficiency. A prospective examination was conducted of fat-stimulated release of pancreatic polypeptide (PP), cholecystokinin (CCK), and neurotensin. Seventy-two-hour fecal fat determination, endoscopic retrograde pancreatography (ERP), and the bentiromide-PABA test were used to correlate the clinical stage of disease. The ERP was classified as positive only if the changes were advanced (or "marked") according to the Cambridge Classification. Five patients were defined to have mild disease, 13 moderate, and 15 severe. Any patient with clinical evidence of chronic pancreatitis and ERP changes that were less than advanced and had normal fecal fat and bentiromide tests received a grade of mild. Patients with one abnormal test were graded moderate, and those with two or three abnormal results were graded severe. In the 33 patients, the integrated 60-minute release of pancreatic polypeptide (PP) was 37.4 +/- 6.1 ng-60 min/ml in those five patients with mild disease, 102.3 +/- 10.3 ng-60 min/ml in the 13 patients with moderate disease, and 7.6 +/- 2.2 ng-60 min/ml in the 15 patients with severe disease. The integrated 60-minute release of neurotensin was 3.8 +/- 0.4 ng-60 min/ml in mild disease, 2.0 +/- 0.3 ng-60 min/ml in moderate disease, and 0.2 +/- 0.1 ng-60 min/ml in severe disease. CCK release did not correlate with the severity of disease. Enhanced release of PP appeared to correlate well with moderate stage of chronic pancreatitis, and depressed PP release with severe disease. Stimulated levels of PP and neurotensin appear to be useful in the diagnosis and staging of chronic pancreatitis. It is concluded that measurement of fat-stimulated release of PP and neurotensin may be useful to assess severity of disease in patients with chronic pancreatitis.

Adult↗