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Biomedical subjects

F R Burton

Publications and source records attributed to F R Burton.

At least 19 recordsLinked to original sources

The effect of midazolam on the normal sphincter of Oddi: a controlled study.

BACKGROUND AND STUDY AIMS: Midazolam HCl (Versed) is often used for intravenous conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP) and is increasingly used in endoscopic sphincter of Oddi (SO) manometry. The effect of medications on SO motility should be fully characterized if they are to be used during SO manometry. There has been controversy as to whether midazolam influences SO motility. The aim of this study was to determine the effect of midazolam on the normal SO. PATIENTS AND METHODS: The study population consisted of 60 patients presenting with recurrent abdominal pain who were found to have SO basal pressure of less than 40 mmHg on SO manometry. ERCP was performed in the standard fashion using a pneumohydraulic capillary perfused triple-lumen catheter system in a stationary pull-through method from the pancreatic and common bile ducts. In the test group 30 patients received 2 mg midazolam intravenously while the 30 patients in the control group received intravenous saline. SO manometry was performed, with recording of the basal pressure, phasic pressure, phasic amplitude, phasic frequency and ductal pressure before and 3 min after the intravenous infusion. The changes in basal, phasic and duct pressure as well as phasic frequency before and after the administration of saline and midazolam were compared. RESULTS: Midazolam causes a small but statistically significant reduction in basal and peak SO pressure (4 and 19 mmHg respectively), compared with saline. Diagnostic concordance (normal vs. abnormal) between the basal sphincter pressure before and after midazolam was seen in 100 % of patients. Midazolam does not significantly affect phasic amplitude, phasic frequency or duct pressure. CONCLUSIONS: Midazolam does not have a clinically significant influence on the accuracy of SO manometry in identifying normal sphincteric motility.

Abdominal Pain↗

Small bowel perforation from a migrated biliary stent.

Stenting of the biliary tract is performed for a variety of benign and malignant disorders. Although uncommon, proximal and distal migration of these stents is known to occur. We report a case of jejunal perforation from a distally migrated biliary stent.

Biliary Tract Surgical Procedures↗

Repetitive self-limited acute pancreatitis induces pancreatic fibrogenesis in the mouse.

The role of repetitive acute injury in the pathogenesis of chronic pancreatitis remains unknown. To determine if repetitive injury induced by pancreatic hyperstimulation would reproduce the characteristic features of human chronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 microg/kg/hr x 6 hr, for 10 weeks. Procollagen alpha1(I) mRNA was markedly increased by week 2. Sirius red staining of interstitial collagen demonstrated progressive accumulation of extracellular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and dilatation of intraacinar lumina also developed. Electron microscopy demonstrated the presence of stromal cells in areas of fibrosis with morphologic characteristics of pancreatic stellate cells. These findings demonstrate that, in a murine model, repetitive acute injury to the pancreas by hyperstimulation can reproduce the major morphological characteristics of human chronic pancreatitis.

Acute Disease↗

Effect of octreotide on stimulated insulin release from pancreatic tissue slices.

This study was designed to investigate a possible mechanism of action by which octreotide acetate causes insulin suppression in the denervated pancreas. Canine tissue slices were placed in a pH-adjusted medium with varying concentrations of glucose and octreotide acetate: Experiment 1, 30 min in basal medium with 0.6 mg/ml glucose; Experiment 2, addition of 6.0 mg/ml glucose; Experiment 3, addition of 4 microg octreotide acetate/70 ml (comparable to 100 microg/25 kg body weight); Experiment 4, addition of 16 microg octreotide acetate/70 ml; Experiment 5, incubation with 6.0 mg glucose/ml and 4 microg octreotide acetate/70 ml; Experiment 6, incubation with 6.0 mg glucose/ml and 16 microg octreotide acetate/70 ml; Experiment 7, preincubation with 4 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml; and Experiment 8, preincubation with 16 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml. Medium levels of insulin, glucagon, and amylase were collected at intervals during the incubation periods. There was an appropriate increase in the rate of insulin release to glucose stimulation in the high-glucose (6.0 mg/ml) group. There was no significant inhibition of basal or glucose-stimulated insulin release with either simultaneous or pretreatment of the canine pancreatic tissue slices with either concentration of octreotide acetate. These studies support an indirect mechanism by which octreotide acetate exerts its inhibitory effect on endocrine and exocrine function in the canine pancreas transplant model.

Amylases↗

Evidence for the anorexia of aging: gastrointestinal transit and hunger in healthy elderly vs. young adults.

Animal studies suggest that aging is associated with anorexia and disordered gastrointestinal transit. To determine whether there is a relationship between the effects of aging on appetite and gastrointestinal transit in humans, 19 young (age 23-50 yr) and 14 elderly (age 70-84 yr) normal volunteers underwent measurements of 1) desire to eat, hunger, and fullness (visual analog scales); 2) gastric emptying (scintigraphy); 3) orocecal transit (breath hydrogen); 4) total gut transit (radiopaque markers); and 5) autonomic nerve function (cardiovascular reflexes). We found that, postprandially, elderly subjects had less desire to eat (P < 0.05) and less hunger (P < 0.05), but not a significantly greater fullness than younger subjects. Gastric emptying (50% emptying time) for solid (182 +/- 26 vs. 127 +/- 13 min, P < 0.05) and liquid (47 +/- 4 vs. 35 +/- 3 min, P < 0.05) meal components was slower in elderly subjects. Postprandial hunger was inversely related (r = -0.39, P < 0.05) to solid gastric emptying. There were no significant differences in orocecal and total gut transit times between the two groups. Autonomic nerve function was abnormal in 11 elderly but none of the young subjects (P < 0.01). We conclude that aging is associated with 1) diminished desire to eat and hunger, 2) slowing of solid and liquid gastric emptying, 3 no change in orocecal and total gut transit, and 4) autonomic nerve dysfunction. The slowing of gastric emptying may contribute to anorexia in aging subjects.

Adult↗

Exocrine effects of the CCK antagonist L-364,718 in canine pancreatic autografts.

This study evaluated the effect of the cholecystokinin antagonist L-364,718 on exocrine secretion in canine pancreatic autografts with pancreaticocystostomies. Urinary (autograft) amylase (U/min) and bicarbonate (mmole/min) secretion, over a 6 hr interval, were determined in the basal state (Group A), after a bolus injection of 20 nmoles/kg of L-364,718 (Group B), during a continuous cholecystokinin octapeptide (OP-CCK) infusion at 125 ng/kg/hr either alone (Group C), with a bolus injection of 20 nmoles/kg (Group D), or 30 nmoles/kg (Group E), of L-364,718 1 hr before initiating OP-CCK, or 20 nmoles/kg of L-364,718 1 hr after initiating OP-CCK (Group F). L-364,718 had no effect on basal or OP-CCK-stimulated secretion of bicarbonate. Basal amylase secretion was decreased 1 hr after L-364,718 and remained significantly lower than controls throughout the study interval. When compared to Group C (280.3 +/- 48.6), OP-CCK-stimulated amylase secretion was significantly lower for the first hour after L-364,718 in both Group D (157 +/- 46.7) and Group E (31.9 +/- 11.6). In Group E, 2, 3, and 4 hr post-L-364,718 amylase releases were 60.2 +/- 19.7, 77.7 +/- 25.1, and 87.2 +/- 28.3 compared to 335.5 +/- 85.9, 291.0 +/- 21.8, and 289.9 +/- 45.7 in Group C indicating a sustained significant inhibition of stimulated autograft amylase secretion with the higher L-364,718 dosage. In Group F, no significant change in amylase secretion was demonstrated, indicating that L-364,718 must be administered prior to CCK stimulation to be effective. These studies demonstrate that L-364,718 has a dose dependent, inhibitory effect on basal, and OP-CCK-stimulated amylase secretion in a denervated autograft model. The therapeutic potential of L-364,718 and other CCK receptor antagonists in pancreatic transplantation warrants further study.

Amylases↗

Effect of L-364,718 on pancreatic endocrine function following partial pancreatectomy.

This study was designed to determine the effect of a potent cholecystokinin antagonist, L-364,718, on canine pancreatic endocrine function following partial pancreatectomy. Plasma glucose, insulin, and glucagon were determined over a 2-hr interval following an intravenous bolus of 0.5 g/kg glucose in a 50% solution. The following groups were established: normal animals (group A, n = 5), normal animals pretreated with 20 nmole/kg L-364,178 (group B, n = 5), partially pancreatectomized animals (group C, n = 5), and partially pancreatectomized animals pretreated with 20 nmole/kg L-364,178 (group D, n = 5). In contrast to animals with an intact pancreas, pretreatment with L-364,718 following partial pancreatectomy resulted in a significant decrease in peak insulin (group C = 132.8 +/- 13.0 microU/ml vs Group D = 90.4 +/- 16.1 microU/ml, P < 0.05) and the basal-to-peak insulin difference (group C = 111.9 +/- 11.5 microU/ml vs group D = 77.5 +/- 16.6 microU/ml, P < 0.05). Despite this, the rate of glucose utilization (K value) was significantly increased in the partially pancreatectomized animals given the antagonist (group C = -1.22 +/- 0.22%/min vs group D = -2.79 +/- 0.427%/min) and there were no significant differences in basal or peak glucose when comparing the groups given L-364,718 with the groups given placebo (group A vs B and group C vs D). Thus, the CCK antagonist L-364,718 significantly decreases peak insulin in partially pancreatectomized animals but not in nonoperative control animals. There is a paradoxical increase in the rate of glucose utilization but no effect on glucose homeostasis. The effect of this antagonist in other models of reduced islet cell reserve (i.e., pancreas transplantation) remains to be determined.

Animals↗

Effect of somatostatin and octreotide acetate on OP-CCK-stimulated exocrine secretion in the denervated canine pancreas.

Somatostatin and its analogue, octreotide acetate (Sandostatin), have been demonstrated to suppress exocrine secretion in a denervated canine pancreatic autograft model. To help define this inhibitory mechanism, the effect of these agents on cholecystokinin (CCK)-stimulated acinar cell secretion was evaluated. In vitro assessment evaluated the effect of somatostatin on octapeptide (OP)-CCK-stimulated amylase release of pancreatic tissue slices. In vivo assessment employed animals with pancreatic autografts and pancreaticocystostomies, evaluating the effect of a bolus intravenous injection of 100 micrograms of octreotide acetate on the basal and OP-CCK-stimulated (125 ng/kg/h) secretion of urinary (autograft) amylase and bicarbonate. Incubation of tissue slices with 0.16, 0.24, or 0.32 microgram/ml somatostatin had no significant effect on in vitro OP-CCK-simulated amylase release. Intravenous octreotide acetate resulted in a significant decrease in the basal rate of amylase secretion but had no significant effect on OP-CCK-stimulated autograft amylase or bicarbonate release. These studies demonstrate that octreotide acetate has an in vivo inhibitory effect on basal amylase release of pancreatic autografts but cannot counteract maximal stimulation with exogenous OP-CCK. Also, somatostatin does not inhibit OP-CCK-stimulated acinar cell secretion of pancreatic tissue slices. These results indicate that the exocrine inhibition produced by somatostatin analogues in the grafted pancreas occurs via an indirect mechanism.

Amylases↗

Consensus statement: octreotide dose titration in secretory diarrhea. Diarrhea Management Consensus Development Panel.

Octreotide is an effective therapeutic option in controlling secretory diarrhea of varied etiology. However, marked patient-to-patient differences in the antidiarrheal effects necessitate titration of octreotide dose in individual patients to achieve optimal symptom control. A consensus development panel established guidelines for octreotide dose titration in patients with secretory diarrhea. Overall, the panel recommended an aggressive approach in selecting the initial octreotide dose and in making subsequent dose escalations in patients with secretory diarrhea due to gastrointestinal tumors (eg, carcinoids, VIPomas), AIDS, dumping syndrome, short bowel syndrome, radiotherapy, or chemotherapy. To avoid hypoglycemia in patients with diabetes mellitus-associated secretory diarrhea, the panel recommended a low initial octreotide dose and a conservative titration regimen with close monitoring a blood glucose levels. The end point of therapy should focus on a reduction in diarrhea (frequency of bowel movements or stool volume) rather than normalization of hormonal profile. Overall, octreotide is well tolerated; principal side effects are transient injection site pain and gastrointestinal discomfort. For many patients with secretory diarrhea, octreotide therapy is expected to improve the overall health and quality of life and in the long run will lessen health care costs.

Carcinoid Tumor↗

The endoscopic diagnosis of iliac colonic fistula and review of literature.

Although the efficacy of upper gastrointestinal endoscopy in the diagnosis of a graft-enteric fistula is defined, the clinical utility of colonoscopy in this problem is not well described. We report a case of a 65-yr-old white male with gastrointestinal bleeding and a suspected graft-enteric fistula which was diagnosed by an immediate preoperative colonoscopic examination. The colonoscopy performed under general anesthesia in the operating room not only documented the presence and location of the graft colonic fistula but also illustrated the necessity for a more radical surgical resection before any planned revascularization. The current literature on the various methods of diagnosis and management of graft-enteric fistula was reviewed.

Aged↗

Common bile duct stones. Detection and removal with endoscopic techniques.

Common bile duct stones are frequently discovered after cholecystectomy or are the first sign of biliary tract disease. Because detection usually requires cholangiography and reoperation is technically difficult, risky, and thus undesirable, nonsurgical methods of identifying and removing the stones have evolved. Among these, endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic retrograde sphincterotomy and stone extraction is the method of choice after cholecystectomy. As newer methods of dealing with biliary disease evolve and alter the spectrum of complications, ERCP will remain an essential diagnostic and management tool.

Cholangiopancreatography, Endoscopic Retrograde↗

Postcholecystectomy syndrome. How to determine if the sphincter of Oddi is the cause.

Recurrence of pain after cholecystectomy is common. This postcholecystectomy syndrome, defined as pain that is unexplained by upper abdominal radiologic and/or endoscopic studies, including endoscopic retrograde cholangiopancreatography, often results from sphincter of Oddi dysfunction. Endoscopic demonstration of elevated sphincter of Oddi pressures is required for diagnosis. The treatment of choice is usually endoscopic sphincterotomy, which yields long-term relief in most patients. Surgical sphincteroplasty or use of calcium channel blockers or long-acting nitrates may be effective if endoscopic sphincterotomy is not suitable.

Cholecystectomy↗

Enteral pancreatic enzyme feedback inhibition of the exocrine secretion of the human transplanted pancreas.

The mechanism of regulation of negative feedback inhibition of the exocrine pancreas and its possible role in decreasing the exocrine secretion of the grafted human pancreas is unknown. To evaluate this we studied the effect of oral pancreatic enzymes on the stimulated transplanted pancreatic exocrine secretion in eight patients with allograft pancreaticocystostomies. After an 8-hr fast, all graft exocrine secretions via graft stent, fistula, and urinary anastomosis were collected for a 1-hr basal period. A standard 300-ml Lundh test meal was then ingested, and all exocrine secretions were collected in 30-min intervals for 3 hr. This test was repeated with 6 capsules of pancrelipase (24,000 units of lipase, 120,000 units of amylase, and 150,000 units of protease) given with the Lundh test meal. Stent, urine and fistula volume, amylase, and pH were measured for each collection period. The total 3-hr amylase secreted after the test meal and the test meal plus pancrelipase were compared. The period of peak amylase secretion after the test meal alone was compared with the same period after the test meal plus pancrelipase and the premeal basal period. The total amylase decreased 34% from 5550 +/- 1000 to 3680 +/- 740 IU/3 hr (P < .03) with pancrelipase. The peak amylase secretion decreased 63% from 1520 +/- 271 to 567 +/- 185 IU/30 min (P < .02) with the addition of pancrelipase to the test meal. Pancrelipase eliminated all meal-stimulated amylase secretion with the mean secretion 16% below the basal secretion of 674 +/- 117 IU/30 min. We conclude that pancreatic negative feedback inhibition significantly decreases meal-stimulated and basal exocrine secretion in the transplanted human pancreas.

Amylases↗

Obstructive jaundice. Nonsurgical options for 'surgical' jaundice.

The development of nonoperative methods of biliary drainage has altered traditional concepts regarding management of medical and surgical jaundice. Patients with newly diagnosed obstructive jaundice typically are elderly and have an unresectable neoplasm. Because surgical cure is often impossible and operation is usually risky in such patients, decompression of the biliary tree by endoscopic retrograde cholangiopancreatography and endoscopically inserted biliary stents has become an increasingly popular means of palliation. Percutaneous transhepatic cholangiography and surgical bilidigestive bypass remain important alternatives. Selection of optimal management for the individual patient requires an in-depth evaluation by a skilled team consisting of the primary care physician, endoscopist, interventional radiologist, and surgeon.

Aged↗

The effect of octreotide acetate on meal-stimulated exocrine secretion in canine pancreatic autografts.

Octreotide acetate (Sandostatin), a long-acting somatostatin analogue, has been demonstrated to have an inhibitory effect on exocrine secretion in the neurally intact pancreas. This study was designed to evaluate the effect of this agent on exocrine secretion in the denervated canine pancreas, utilizing animals with pancreatic autografts and functioning pancreaticocystostomies. The rates of secretion of urinary (autograft) amylase (units/min) and bicarbonate (mM/min), over a five-hr interval, were determined in the basal state (group A, n = 10), after a bolus injection of 400 micrograms of Sandostatin (group B, n = 5), after a standard meal (group C, n = 5), or a meal preceded by 400 micrograms of Sandostatin (group D, n = 5). Basal secretion of amylase was decreased for 4 hr following Sandostatin, although this decrease was not significant. Conversely, basal bicarbonate secretion was not inhibited by Sandostatin. When compared with group C (22.4 +/- 3.2), a significant inhibition of meal-stimulated amylase release was demonstrated in group D (5.4 +/- 0.21, P = 0.0006) during the first hour after Sandostatin was given. This inhibition remained significant at 2 hr (group C = 38.5 +/- 5.2 versus group D = 9.4 +/- 0.8; P = 0.0006) and 3 hr (group C = 38.6 +/- 6.3 versus group D = 17.5 +/- 0.9; P = 0.0108) after Sandostatin was given. In addition, meal-stimulated bicarbonate secretion was significantly inhibited for 2 hr following Sandostatin (group C = 0.19 +/- 0.03 versus group D = 0.07 +/- 0.02, P = 0.0096; and group C = 0.23 +/- 0.03 versus group D = 0.10 +/- 0.01, P = 0.0018, respectively). These studies demonstrate that Sandostatin has a profound inhibitory effect on meal-stimulated enzyme and bicarbonate release in a denervated canine autograft model. Although the site of action of this agent remains to be defined, Sandostatin may have therapeutic potential in clinical pancreas transplantation.

Amylases↗

Acute upper gastrointestinal bleeding in elderly persons.

We have seen that UGI bleeding is a serious and apparently growing problem for seniors. Of special concern in the older patient are the frequency with which serious peptic disease presents silently, the limitation frequently imposed on adequate pain relief from NSAIDs, and the higher complication rates from most of the causes of UGI bleeding. Care of the elderly would be enhanced by research focused on defining those older patients most at risk of experiencing NSAID-induced peptic complications, improved methods for preventing or treating NSAID-induced ulceration that are well tolerated and cost-effective, and better regimens for preventing the recurrence of ulcers and UGI bleeding in these patients. In regard to the last, future investigation of the role of H. pylori, methods for successfully eliminating the organism, and the effect of eradication on patients' subsequent course may be particularly helpful.

Age Factors↗