Biomedical subjects

A S Fink

Publications and source records attributed to A S Fink.

At least 37 records · Page 2Linked to original sources

PubMed1994

Inhibition of pancreatic exocrine secretion by galanin.

The influence of extrapancreatic nerves on the inhibition of meal- and secretogogue-induced pancreatic secretion by galanin was studied in conscious dogs. Chronic pancreatic fistulae were created in five mongrel dogs and a second group of five dogs also underwent complete pancreatic denervation. After recovery, galanin dose response (150-1,200 pmol/kg/h) revealed that 600 pmol/kg/h was the lowest dose of galanin to significantly inhibit pancreatic exocrine secretion. Pancreatic responses to a mixed meal, cholecystokinin (CCK) dose response (12.5-200 ng/kg/h), and secretin dose response (16-500 ng/kg/h) were determined. The experiments were then replicated with a continuous background infusion of galanin (600 pmol/kg/h). Galanin inhibited meal-, CCK-, and secretin-induced bicarbonate outputs in both the innervated and denervated pancreas. Galanin also inhibited meal- and CCK-induced protein responses in both groups. We conclude that extrapancreatic nerves do not mediate the inhibitory effects of galanin.

Animals↗

PubMed1994

Candida in pancreatic infection: a clinical experience.

Pancreatic infection remains a significant clinical problem, with substantial morbidity and mortality. Published case reports of Candida species identified in these infections prompted a review of 17 consecutive patients recently treated for peripancreatic infection by scheduled relaparotomy. Six patients were transferred from other hospitals, all having undergone prior operative intervention (median stay elsewhere: 58 days). The 11 other patients underwent initial operation an average of 14 days after admission. Candida species were identified in the initial operative cultures of 5 patients (29%), three of whom had undergone previous drainage at other hospitals. Two patients (11.7%) had Candida identified at subsequent operation. Six patients were treated with Amphotericin B for a median of 12 days (range 6-32) and a median dosage of 420 mg (range 225-830 mg). All patients were cleared of their Candida infection, but three subsequently died, for an overall mortality of 17.6%. Candida infected patients suffered a 42 per cent mortality. Our series supports the suspicion that Candida is much more frequent (41% of patients) than previously recognized in peripancreatic sepsis, and is commonly acquired after the initial operation. Amphotericin B therapy is effective in clearing Candida infection, but affected patients have a high associated mortality.

Acute Disease↗

PubMed1994

Pancreatic denervation does not influence glucose-induced insulin response.

BACKGROUND: Pancreatic transplantation results in denervation and loss of splanchnic venous drainage and inflicts numerous metabolic abnormalities. However, it is unclear whether denervation or loss of splanchnic venous drainage is responsible for the observed metabolic abnormalities. METHODS: To discern denervation's role in these abnormalities, four mongrel dogs underwent extrinsic pancreatic denervation with preservation of splanchnic venous drainage. These animals, as well as four innervated control subjects, underwent standardized enteral and intravenous glucose tolerance testing. In addition, hyperglycemic clamps that maintained stable serum glucose elevations at either 2.8 or 8.3 mmol/L above basal were also performed. RESULTS: Prestimulated glucose (90.4 +/- 2.7 vs 92.6 +/- 4.9 mg/dl) and insulin levels (6.8 +/- 1.7 vs 8.5 +/- 1.4 muU/ml) did not differ between innervated and denervated groups. Integrated incremental enteral glucose (5320 +/- 1900 vs 7790 +/- 2000 mg/dl) and insulin (2565 +/- 350 vs 2836 +/- 598 muU/ml) levels did not differ between groups. Integrated incremental intravenous glucose (3680 +/- 400 vs 3950 +/- 1000 mg/dl) and insulin (741 +/- 70 vs 1053 +/- 326 muU/ml) levels also did not differ. During glucose clamp studies, time-weighted 60 to 120-minute insulin levels (2.8 mmol/L, 30 +/- 5.0 vs 24 +/- 4.8 muU/ml; 8.3 mmol/L, 57 +/- 5.9 vs 50 +/- 9.8 muU/ml) did not differ between groups. In addition, glucose disposal, cyclic insulin release, and insulin sensitivity indexes were unchanged by denervation. CONCLUSIONS: Extrinsic pancreatic neural elements are not necessary for cyclic insulin release in response to enteral or parenteral glucose challenge or physiologic and pharmacologic hyperglycemia. These findings suggest that the previously described posttransplantation glucose and insulin abnormalities are not attributable to denervation.

Animals↗

PubMed1993

Peptide YY inhibits pancreatic secretion via cholinergic pathways.

The influence of extrapancreatic nerves and intrapancreatic cholinergic activity on the inhibition of pancreatic exocrine secretion by peptide YY (PYY) was studied in conscious dogs. Chronic pancreatic fistulae were created in five mongrel dogs while a second group of five dogs also underwent complete pancreatic denervation. After recovery, a continuous infusion of secretin (62 ng/kg/hr) and cholecystokinin (50 ng/kg/hr) was administered over 2 hr. An infusion of PYY (400 pm/kg/hr) was then given randomly, during either the first or second experimental hour. The experiments were then replicated with a continuous background infusion of (90 micrograms/kg/hr) bethanechol, a cholinergic agonist. The secretin/cholecystokinin-induced bicarbonate and protein outputs were significantly inhibited by PYY in both the innervated and denervated animals. In the denervated animals, bethanechol eliminated the inhibitory effects of PYY. We conclude that extrapancreatic nerves do not mediate the inhibitory effects of PYY. The results suggest that PYY inhibits secretin/cholecystokinin-induced pancreatic response by an intrapancreatic cholinergic mechanism.

Animals↗

PubMed1993

Protective effect of RibCys following high-dose irradiation of the rectosigmoid.

UNLABELLED: Ribose-cysteine (RibCys) is a prodrug of L-cysteine that stimulates glutathione biosynthesis. Increased glutathione levels have been shown to have a protective effect against radiation-induced injury and oxidative stress. Surface oximetry has previously been used successfully to predict anastomotic leakage. PURPOSE: The following study was done to evaluate the protective effect of RibCys and the predictive value of PtO2 determinations in a swine model. METHODS: Domestic swine were divided into three groups: Group A served as a nonradiated control; Group B received 6,000 to 6,500 rad to the rectosigmoid; and Group C received RibCys (1 g/kg) prior to receiving 6,000 to 6,500 rad. Radiated animals and controls underwent rectosigmoid resection after a three-week rest period. Intraoperative anastomotic PtO2 was checked with a modified Clark electrode. Anastomoses were evaluated radiographically at three and seven days; animals were sacrificed, and bursting strength was recorded at 10 days. RESULTS: Mean bursting pressures were 243.8 +/- 59.4, 199.5 +/- 37.8, and 209.5 +/- 54.9 mmHg (NS) for Groups A, B, and C, respectively. Anastomotic PtO2 ranged from 19 to 98 mmHg and could not be correlated with anastomotic leaks or bursting pressure. There were 11/15 radiation-related deaths and leaks (eight deaths and three leaks) in the radiated group and 4/12 radiation-related deaths and leaks (three deaths and one leak) in the group receiving radiation and RibCys (P < 0.04). CONCLUSIONS: 1) RibCys protected animals against radiation-related deaths and anastomotic leaks following high doses of pelvic irradiation; 2) anastomotic PtO2 levels did not correlate with anastomotic healing in this model.

Anastomosis, Surgical↗

PubMed1993

Somatostatin inhibits secretin-induced canine pancreatic response via a cholinergic mechanism.

BACKGROUND: Somatostatin inhibits pancreatic exocrine secretion in intact animals but not in vitro, suggesting an indirect effect. The present study examined the influence of extrapancreatic nerves and intrapancreatic cholinergic activity on somatostatin-induced inhibition of pancreatic exocrine secretion in conscious dogs. METHODS: Seven dogs underwent extrapancreatic denervation and creation of pancreatic fistulae, while a second group of 6 dogs had pancreatic fistulae created without denervation. The pancreatic responses to graded doses of secretin (16-500 ng.kg-1.h-1), both alone and during background infusions of somatostatin-14 (400 and 800 pmol/L.kg-1.hr-1), were determined in all dogs. The secretin dose response was then repeated with a continuous infusion of bethanechol (90 micrograms.kg-1.h-1) both with and without somatostatin-14 (800 pmol/L.kg-1.h-1). RESULTS: Secretin-induced bicarbonate and protein outputs were significantly inhibited by somatostatin-14 in both the innervated and denervated animals. The inhibitory effects of somatostatin-14 were partially reversed by bethanechol in the innervated animals and completely reversed in the denervated animals. Bethanechol alone potentiated secretin-induced bicarbonate output from both the innervated and denervated pancreas. CONCLUSIONS: The data suggest that extrapancreatic nerves do not mediate the inhibitory effects of somatostatin-14. Rather, somatostatin-14 appears to inhibit secretin-induced pancreatic response by an intrapancreatic cholinergic mechanism.

Animals↗

PubMed1993

Effect of pancreatic denervation and atropine on the pancreatic response to secretin.

To study the influence of extrapancreatic nerves and intrapancreatic cholinergic activity on the pancreatic response to secretin, six dogs underwent extrapancreatic denervation and creation of pancreatic fistulae. A second group of six dogs had pancreatic fistulae created without pancreatic denervation. The pancreatic exocrine response to graded doses of secretin (16-500 ng/kg/h) was determined, both alone and during a background infusion of cholecystokinin-octapeptide (CCK8, 50 ng/kg/h). All studies were replicated during administration of atropine (10 micrograms/kg/h). Secretin-induced bicarbonate output was significantly inhibited by atropine in both the innervated and denervated groups. Combined secretin and CCK8 elicited a dose-dependent increase in bicarbonate output and a sustained increase in protein output in both groups, regardless of atropine. In addition, potentiation of secretin-induced bicarbonate output by CCK8 was observed despite both extrinsic pancreatic denervation and administration of atropine. We conclude that endogenous intrapancreatic cholinergic activity influences the pancreatic response to secretin. Potentiation of secretin-induced bicarbonate output by CCK, however, is not dependent on neural mediation.

Animals↗

PubMed1993

Anatomical and morphological evaluation of pacemaker lead compression.

In recent years, pacemaker lead failure due to compressive damage has been reported with increasing frequency. To document the mechanism of this failure, we evaluated explanted mechanically damaged leads with electrical testing, optical microscopy, and in some cases, scanning electron microscopy (SEM). In addition, we performed an autopsy study to measure the compressive loads on catheters placed percutaneously through the costoclavicular angle, as well as by cephalic cutdown. Of the 49 explanted compression damaged leads with enough clinical data for analysis, all had been placed by percutaneous subclavian puncture. Our autopsy data confirmed the significant increase in pressures generated in the costoclavicular angle for medial percutaneous subclavian catheterization (126 +/- 26 mmHg) compared to a more lateral percutaneous subclavian puncture (63 +/- 15 mmHg) or a cephalic cutdown (38 +/- 13 mmHg) (P < 0.01). In vivo coil compression testing documented loads up to 100 pounds per linear inch of coil and a compressive morphology by SEM identical to that seen in the clinical explants. Pacemaker leads appear to be susceptible to compression damage when placed by subclavian venipuncture. When possible, leads should be placed such that they avoid the tight costoclavicular angle.

Bloodletting↗

PubMed1992

Effects of intraluminal peptide YY on pancreatic function.

Peptide YY (PYY) is released postprandially into both the circulation and the distal intestinal lumen. While circulating PYY inhibits pancreatic secretion and insulin release, the effects of intraluminal PYY on pancreatic function are unknown. The aim of the present study was to evaluate the effect of exogenous, intraileal luminal PYY on pancreatic exocrine function and fasting glucose levels. Chronic pancreatic and ileal fistulae (50 cm from the ileocecal valve) were created in nine mongrel dogs. The animals were given intravenous infusions of secretin (125 ng/kg/h) and cholecystokinin octapeptide (CCK-8, 50 ng/kg/h) for four hours. At the beginning of the second hour, either normal saline or PYY, at low [physiologic (2 ng/min)] or high [supraphysiologic (50 ng/min)] levels, was infused antegrade into the ileal fistula for two hours. Pancreatic juice was collected for PYY and glucose levels. Ileal luminal PYY infusions had no effect on pancreatic bicarbonate or protein output. Fasting serum PYY and glucose concentrations were unaffected by either dose of intraluminal PYY. We conclude that ileal luminal PYY does not influence pancreatic exocrine function or fasting glucose levels.

Animals↗

PubMed1992

Role of the distal pancreas in pancreatic polypeptide release.

In two previous studies, postprandial pancreatic polypeptide (PP) release was inhibited when pancreatic denervation was combined with distal pancreatectomy. In contrast, postprandial PP release was unaffected by pancreatic denervation without a distal pancreatectomy. These findings suggested a role for the distal pancreas in regulation of postprandial PP release. To examine this possibility, we performed distal pancreatectomy on four mongrel dogs. Pancreatic polypeptide response to i.v. insulin (0.5 U/kg), a meal, and an infusion of cholecystokinin octapeptide (CCK-8; 50 ng/kg/h) were measured in conscious dogs before and after distal pancreatectomy. Insulin-induced hypoglycemia stimulated PP release both preoperatively (47.0 +/- 8.8 ng.[0-120]min/ml) and postoperatively (61.6 +/- 9.2 ng.[0-120]min/ml). Ingestion of a meal also evoked significant PP release preoperatively (85.8 +/- 22.1 ng.[0-180]min/ml) and postoperatively (105.8 +/- 42.2 ng.[0-180]min/ml). CCK-8 elicited only a small increase in circulating PP, which was not influenced by distal pancreatectomy. These findings demonstrate that distal pancreatectomy does not alter PP response to insulin, a meal, or CCK-8.

Animals↗

PubMed1991

The effect of pancreatic polypeptide and peptide YY on pancreatic blood flow and pancreatic exocrine secretion in the anesthetized dog.

Pancreatic polypeptide (PP) and peptide YY (PYY) are inhibitors of pancreatic exocrine secretion in vivo but not in vitro, which suggests intermediate mechanisms of action. To examine the role of pancreatic blood flow in these inhibitory effects, xenon-133 gas clearance was used to measure pancreatic blood flow while simultaneously measuring pancreatic exocrine secretion. PP or PYY (400 pmol/kg/h) was administered during the intermediate hour of a 3-h secretin (125 ng/kg/h)/cholecystokinin octapeptide (CCK-8) (50 ng/kg/h) infusion. Exocrine secretion and pancreatic blood flow during the PP or PYY hours were compared with that observed in the first and third hours of the secretin/CCK-8 infusion. PP and PYY significantly inhibited secretin/CCK-8-induced pancreatic exocrine secretion. In addition, PYY (but not PP) significantly reduced pancreatic blood flow during secretin/CCK-8 stimulation. Nevertheless, there was no correlation between pancreatic blood flow and bicarbonate or protein outputs. It is concluded that changes in pancreatic blood flow do not mediate the inhibitory effects of PP or PYY on the exocrine pancreas.

Animals↗

PubMed1991

Endoscopic intervention in pancreatitis.

This overview clearly documents the critical diagnostic and therapeutic role for endoscopic intervention in pancreatitis. Further, although at the forefront of endoscopic development, the new therapeutic techniques discussed offer promise, suggesting cautious optimism. Their ultimate role in treatment of pancreatic disorders must await clarification of appropriate indications, safety, efficacy, and long-term benefit.

Acute Disease↗

PubMed1991

Pancreatic polypeptide and peptide YY inhibit the denervated canine pancreas.

Pancreatic polypeptide and peptide YY are inhibitors of pancreatic exocrine secretion in vivo but not in vitro, which suggests secondarily mediated mechanism(s) of action. To determine the role of extrinsic neural and intrinsic cholinergic elements on this inhibitory effect, a total of nine dogs underwent two-stage extrapancreatic denervation and creation of a chronic pancreatic fistula. After recovery, pancreatic polypeptide or peptide YY (400 pmol/kg/h) was administered during the intermediate hour of a 3-hour secretion (125 ng/kg/h)/cholecystokinin (50 ng/kg/h) infusion. Exocrine secretion pancreatic polypeptide or peptide YY hours was compared with that of the first and third hours. The studies were then repeated during infusion of atropine (10 micrograms/kg/h). Despite extrinsic denervation, pancreatic polypeptide and peptide YY significantly inhibited secretin/cholecystokinin-induced pancreatic output. Although less profound, significant inhibition persisted in the presence of an atropine background. Pancreatic polypeptide or peptide YY infusion also decreased the exocrine response to meal stimulation. We conclude that the inhibitory effects of pancreatic polypeptide and peptide YY are not mediated by extrapancreatic, and possibly not by intrapancreatic cholinergic, neural pathways.

Animals↗

PubMed1990

Periappendicitis is a significant clinical finding.

Periappendicitis has heretofore been regarded as a pathologic curiosity with little clinical significance. In this report, we have reviewed the UCLA experience with periappendicitis. Between 1955 and 1985, resected appendices of 353 patients showed periappendicitis on pathologic examination. Sixty-one of these patients, in whom exploratory surgery was performed for reasons other than acute appendicitis, underwent incidental appendectomy. In 251 of the remaining 292 patients, appendectomy was performed either for pathologically confirmed acute appendicitis or concomitant with treatment of other unsuspected abnormalities discovered intraoperatively. Although the remaining 41 patients were also believed to have acute appendicitis, their resected specimens revealed only periappendicitis. The latter group was composed of 9 males and 32 females, with a mean age of 29 years (range: 6 to 76 years). Twenty-four complications occurred in 18 of these patients (44%). Seven additional operative procedures were required in 5 of the 41 patients (12%). One patient died (2%). We conclude that identification of periappendicitis in the patient presumed to have acute appendicitis is of definite clinical significance and may merit further clinical investigation.

Acute Disease↗

PubMed1990

Meal-induced pancreatic polypeptide release in a validated pancreatic denervation model: a role for the distal pancreas?

In previous studies, postprandial pancreatic polypeptide (PP) release was diminished when pancreatic denervation was combined with distal pancreatectomy in animals without chronic fistulae. In contrast, postprandial PP release was reported to be unchanged when the pancreas was denervated without performing a distal pancreatectomy. These findings were unexpected given that the distal pancreas is a PP-poor region. To clarify this issue, we performed extrinsic pancreatic denervation, distal pancreatectomy, and insertion of chronic pancreatic fistulae in nine mongrel dogs. Insulin (0.5 U/kg) and meal-stimulated PP release were measured pre- and postoperatively. In addition, insulin- and meal-induced exocrine secretion was measured postoperatively. Preoperatively, insulin-induced hypoglycemia stimulated significant PP release (80,553 +/- 18,540 pg/min/ml). This response was completely abolished postoperatively (-1,669 +/- 5,054 pg/min/ml). Exocrine secretion did not increase above basal levels after administration of insulin in postoperative animals. These findings suggest adequate pancreatic denervation. Ingestion of a meal evoked significant PP response preoperatively (97,909 +/- 18,394 pg/min/ml). Postoperatively, the response was significantly blunted (17,231 +/- 6,407 pg/min/ml). This finding is in contrast to a previous report using a similar experimental preparation without distal pancreatic resection. We speculate that although the distal pancreas is PP-poor, it may play a role in the regulation of PP release from the PP-rich pancreatic head.

Animals↗

PubMed1989

Intraluminal calcium binding does not mediate fatty acid-induced pancreatic bicarbonate secretion.

Since the chain length dependency of fatty acid-induced pancreatic exocrine secretion parallels that of fatty acid-induced inhibition of gastric emptying, similar mechanisms of action may be involved. An earlier study suggested that binding of calcium might mediate fatty acid-induced inhibition of gastric emptying. This study investigated possible mediation of fatty acid-induced pancreatic secretion by calcium binding. Pancreatic secretory response to intraduodenal administration of dodecanoate and various calcium chelators (sodium EDTA, calcium-saturated EDTA, sodium dodecyl sulfate, sodium dioctyl sulfosuccinate, and sodium taurocholate) was studied in three dogs equipped with chronic pancreatic fistulae. Calcium affinity of the various test solutions was quantitated by titrating aliquots of perfusate against a standard CaCl2 solution. Sodium EDTA was found to be the most potent calcium binder (pKc 8.3); sodium dodecanoate, sodium dodecyl sulfate, and sodium dioctyl sulfosuccinate were moderate calcium binders (pKc 7.3, 7.2, 6.9, respectively), whereas sodium taurocholate and calcium-saturated EDTA were poor calcium binders. Sodium dodecanoate evoked brisk bicarbonate output (0.6-1.6 mEq/15 min). Minimal secretory responses were observed in response to all other agents tested. These findings suggest that calcium binding is not involved in mediation of fatty acid-induced pancreatic bicarbonate secretion.

Animals↗

PubMed1989

Alterations in digestive function caused by pancreatic disease.

Pancreatic exocrine secretion is regulated by a complex interaction of meal-stimulated neurohormonal reflexes. Pancreatic enzyme output must be reduced to less than 10 per cent of normal before fat absorption is appreciably impaired, proving that the pancreas secretes a large surplus of enzymes. Surgical therapy does not improve pancreatic exocrine insufficiency, and partial pancreatic resection frequently precipitates steatorrhea in patients with chronic pancreatitis. Therefore, pancreatic resection should be undertaken cautiously in patients who do not yet have clinically evident exocrine insufficiency. In most patients, oral pancreatic enzymes will control diarrhea secondary to steatorrhea. In others, concurrent administration of an H2 blocker is required to reduce gastric acidity and prevent enzyme inactivation in the stomach. Formulations with an acid-resistant coating are also effective in some patients. However, complete normalization of fat absorption with restoration of body weight and nutritional well-being requires careful management of multiple dietary and behavioral factors, as well as long-term follow-up. Unfortunately, this appears to be an elusive goal, as many patients with chronic pancreatitis continue to die of malnutrition.

Digestion↗

PubMed1989

Comparison of gas clearance and radioactive microspheres for pancreatic blood flow measurement.

Measurement of pancreatic blood flow (PBF) is technically demanding. Although radiolabeled microspheres are considered the "gold standard" for PBF assessment, they have practical limitations. In the current study, H2 and xenon-133 gas clearance techniques were adapted to PBF measurement and compared to radiolabeled microsphere techniques. Simultaneous measurements of PBF were made using either hydrogen or xenon gas washout and radiolabeled microspheres. Measurements were made under basal, vasoconstricted (vasopressin 2U i.v. or nicotine 4 micrograms/kg/h) and stimulated (secretin 125 ng/kg/h or 2 U/kg i.v.) conditions (random order). Mean PBF was 26.9 +/- 5.3, 50.5 +/- 2.3 and 27.6 +/- 5.2 ml/min/100 g basally, 36.9 +/- 8.0, 90.1 +/- 18.9, and 81.7 +/- 14.5 ml/min/100 g in the stimulated state, and 24.2 +/- 7.8, 25.0 +/- 3.5, and 14.9 +/- 7.5 ml/min/100 g in the vasoconstricted state for hydrogen gas clearance, xenon gas clearance, and radiolabeled microspheres, respectively. The H2 clearance technique resulted in tissue trauma, was complicated by frequent electrode displacement, and correlated poorly (r2 = 0.36, p greater than 0.05) with microsphere values. In contrast, xenon clearance measurement had no apparent effect on the pancreas and correlated well (r2 = 0.83, p less than 0.01) with microsphere data. We conclude that xenon clearance offers an attractive, validated alternative to radiolabeled microspheres for measuring pancreatic blood flow.

Animals↗