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S W Ashley

Publications and source records attributed to S W Ashley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Feline model of chronic obstructive pancreatitis: effects of acute pancreatic duct decompression on blood flow and interstitial pH.

BACKGROUND: The mechanism by which duct decompression (DD) relieves pain in patients with chronic pancreatitis (CP) is unknown. CP is associated with increased tissue pressure (IP), low pancreatic microvascular blood flow (PMBF), and interstitial pH (pH(I)). The aims of this study were to examine the effects of acute DD on PMBF, increased IP, and pH(I) in cats with CP. METHODS: The main pancreatic duct was partially obstructed. At 6 weeks PMBF (ml/min/100g H2 gas clearance), IP (mmHg needle electrode), and pH(I) (microelectrode) were measured before and after secretin stimulation. The duct was then opened, and the studies were repeated. RESULTS: PMBF normally increased with secretin stimulation (118 +/- 20 versus 271 +/- 52, P < 0.05). IP was unaltered, and pH(I) decreased as hydrogen ions produced during bicarbonate secretion were dissipated (7.41 +/- 0.01 versus 7.38 +/- 0.01, P < 0.05). In CP, basal PMBF was lower than normal (51 +/- 6 versus 118 +/- 20, P < 0.05) and decreased with stimulation (51 +/- 3.5 versus 31 +/- 3.5, P < 0.05). Basal pancreatic IP was increased (3.47 +/- 0.7 versus 0.05 +/- 0.3, P < 0.05) and increased further with secretory stimulation (3.47 +/- 0.7 versus 4.41 +/- 0.7, P < 0.05) (a compartment syndrome). The low basal pancreatic pH(I) (7.23 +/- 0.02) did not change with secretin stimulation, since bicarbonate secretion was minimal. DD decreased IP (3.66 +/- 0.5 versus 2.81 +/- 0.5, P < 0.05) and increased PMBF (50 +/- 6 versus 79 +/- 6, P < 0.05) and pH(I) (7.24 +/- 0.02 versus 7.34 +/- 0.02, P < 0.05). The normal increase in PMBF after stimulation was restored (79 +/- 6 versus 218 +/- 54, P < 0.05). pH(I) now increased with stimulation (7.34 +/- 0.002 versus 7.37 +/- 0.002, P < 0.05), perhaps due to the marked hyperaemic response. CONCLUSIONS: DD acutely restored basal and stimulated PMBF and IP towards normal. Basal pancreatic pH(I) also improved and reflects the underlying ischaemia.

Animals↗
PubMed1999

Effect of pancreaticojejunostomy on fibrosis, pancreatic blood flow, and interstitial pH in chronic pancreatitis: a feline model.

OBJECTIVE: To study the relation between fibrosis, pancreatic blood flow (PMBF), interstitial pH (pHi), and the effects of pancreaticojejunostomy (PJ) in chronic pancreatitis. BACKGROUND: Chronic pancreatitis is associated with low PMBF and pHi, suggesting the existence of underlying ischemia. METHODS: In cats, the main pancreatic duct was partially obstructed and the animals were studied 2, 4, 6, and 8 weeks later. PJ was performed after 2 and 4 weeks of ductal obstruction and studied 4 weeks later. PMBF and pH were measured before and after stimulation with secretin and cholecystokinin. pHi was measured with microelectrodes, PMBF by hydrogen gas clearance. Histologic analysis of the pancreas with Sirius red (collagen stain) and fast green FCF (noncollagen protein) stains allowed semiquantitative analysis of the ratio between collagen and total protein (C/TP). RESULTS: With the evolution of chronic pancreatitis, there is a progressive increase in the collagen content and C/TP ratio, a reduction in basal PMBF and pHi, and loss of the normal response to stimulation. Early PJ restores collagen content, C/TP ratio, and basal and stimulated PMBF and pHi to normal. PJ performed in established CP returns the C/TP ratio to normal, improves basal PMBF, and restores the normal hyperemic response to secretion. Basal pHi is improved and the "acid tide" associated with secretin returns, but there is still no response to cholecystokinin. CONCLUSIONS: Pancreaticojejunostomy restores the elevated collagen and C/TP ratio to normal and reverses the ischemia present in CP. The authors speculate that restoration of PMBF and its normal response to stimulation allows "regeneration" and restoration of secretory function.

Animals↗
PubMed1999

Paracellular glucose transport plays a minor role in the unanesthetized dog.

Traditionally, intestinal glucose absorption was thought to occur through active, carrier-mediated transport. However, proponents of paracellular transport have argued that previous experiments neglected effects of solvent drag coming from high local concentrations of glucose at the brush-border membrane. The purpose of this study was to evaluate glucose absorption in the awake dog under conditions that would maximize any contribution of paracellular transport. Jejunal Thiry-Vella loops were constructed in six female mongrel dogs. After surgical recovery, isotonic buffers containing L-glucose as the probe for paracellular permeability were given over 2-h periods by constant infusion pump. At physiological concentrations of D-glucose (1-50 mM), the fractional absorption of L-glucose was only 4-7% of total glucose absorption. Infusion of supraphysiological concentrations (150 mM) of D-glucose, D-maltose, or D-mannitol yielded low-fractional absorptions of L-glucose (2-5%), so too did complex or nonabsorbable carbohydrates. In all experiments, there was significant fractional water absorption (5-19%), a prerequisite for solvent drag. Therefore, with even up to high concentrations of luminal carbohydrates in the presence of significant water absorption, the relative contribution of paracellular glucose absorption remained low.

Absorption↗
PubMed1998

Intragastric alcohol causes endothelin release from feline pancreas.

The mechanism by which alcohol causes pancreatic damage is still largely unknown. One important contributory factor may be the endothelins, potent vasoconstricting endothelial-derived peptides. The aim of this study was to examine in vivo endothelin release from the pancreatic vascular endothelium after alcohol ingestion. In anesthetized cats immunoreactive endothelin was measured in serum after instillation of alcohol into the stomach (20 ml, 40%). After intragastric alcohol, a rise in endothelin was seen in pancreatic venous effluent (to a mean of 24.5 +/- 7.7 pg/ml at 60 min). Control serum from the femoral artery exhibited no rise in endothelin (2.11 +/- 1.2 pg/ml). Pancreatic blood flow was significantly decreased in a further group to 93% basal after intravenous infusion of 0.1 nmol/kg ET-1 and to 61% after infusion of 1 nmol/kg ET-1. Portal serum levels of endothelin were 105 pg/ml and 15 pg/ml, respectively, immediately following bolus infusion and decreased to normal levels within 120 sec. We conclude that the serum endothelin rise after intragastric ethanol may be a major factor behind the drop in pancreatic blood flow.

Animals↗
PubMed1998

Ethanol-mediated neutrophil extravasation in feline pancreas.

Ethanol is a common cause of both acute and chronic pancreatitis. Studies in other organs suggest that polymorphonuclear neutrophils activated by ethanol may cause tissue injury in a variety of conditions. The aim of this study was to investigate the effects of ethanol on neutrophil extravasation in the feline pancreas. Pancreata were isolated and perfused at different flow rates with varying concentrations of ethanol in either a physiological or neutrophil depleted perfusate. Neutrophil extravasation was assessed by measuring pancreatic tissue myeloperoxidase (MPO) activity. Ethanol at 2.5% (54.25 mmol/liter) was the lowest concentration that still caused significant neutrophil extravasation (3.1+/-0.8 vs 1.9+/-0.2 units, P<0.05) and was accompanied by an increase in vascular resistance of 15%. Reduction of pancreatic perfusion by 15% did not significantly increase neutrophil extravasation. (1.1+/-0.3 vs 1.6+/-0.2 units, NS) Perfusion of the pancreas with neutrophil-depleted blood containing either ethanol or saline, followed by perfusion with an ethanol-free perfusate, showed an increase in neutrophil extravasation in the ethanol group compared to the control group (3.2+/-0.9 vs 1.9+/-0.2 units, P<0.05). In conclusion, ethanol causes neutrophil extravasation in the feline pancreas independent of blood flow changes and occurs despite the absence of direct neutrophil exposure to ethanol.

Animals↗
PubMed1998

Stenting does not decompress the pancreatic duct as effectively as surgery in experimental chronic pancreatitis.

BACKGROUND: In humans with chronic pancreatitis (CP), pancreatic interstitial pressure (IP) is elevated and pancreatic blood flow (PBF) is reduced. The efficacy of surgical decompression (SD) of the pancreatic duct (ie, pancreaticojejunostomy) is believed to be due to its ability to decrease IP and pancreatic vascular resistance (Rp), which increases PBF. Pancreatic duct stenting (STE) also probably reduces IP and Rp, which may explain its efficacy. The purpose of this study was to compare the efficacy of SD with STE. METHODS: CP in cats was created by narrowing the main pancreatic duct. Six weeks later, CP and normal pancreata were isolated and perfused ex vivo under basal conditions and after secretin stimulation. In normal and CP glands, IP and perfusion pressure were measured and Rp (U) was calculated. In two additional groups, the pancreatic duct was decompressed, either by stenting or by complete transection of the duct with a longitudinal capsulotomy. RESULTS: In CP glands, IP and Rp were increased and secretory output was markedly reduced compared with the normal (0.65 +/- 0.30 mm Hg and 0.46 +/- 0.04 U vs 3.90 +/- 0.80 mm Hg and 1.68 +/- 0.05 U; P < .05). Secretin administration (2 units) increased IP and Rp in CP glands (6.60 +/- 1.10 mm Hg and 2.87 +/- 0.07 U; P < .05), but these values did not chang in normal glands (0.81 +/- 0.20 and 0.53 +/- 0.03 U; NS). STE and SD decreased IP and Rp in CP glands (2.20 +/- 0.20 to 1.0 +/- 0.40 mm Hg and 1.20 +/- 0.015 to 0.90 +/- 0.01 U, respectively; P < .05). Both methods prevented an increase of IP and Rp after secretin administration. IP and Rp decreased to a greater degree following SD, compared with STE (P < .05). CONCLUSIONS: Both STE and SD decreased IP and Rp in this experimental model of CP. However, SD was significantly more effective than STE.

Animals↗
PubMed1998

Diverting loop versus end ileostomy during ileoanal pullthrough procedure for ulcerative colitis.

A two-stage ileoanal pullthrough procedure (IAPP) is often used for patients with ulcerative colitis (UC) requiring proctocolectomy. We analyzed the recent University of California at Los Angeles experience with diverting end and loop ileostomies in patients undergoing a two-stage IAPP. A retrospective analysis of 21 patients with UC undergoing loop ileostomy between March 1992 and March 1995 was performed. Comparison was made with 21 age- and gender-matched patients undergoing end ileostomy between January 1991 and December 1995. There was no mortality or major septic complications. A second laparotomy was required in all patients with end ileostomies, whereas loop ileostomies were closed without abdominal exploration. During ileostomy closure, operative time and mean hospital stay were significantly reduced with the use of loop ileostomy. The time to oral feeding was not significantly different between end and loop ileostomy groups after ileostomy closure. The complication rate after IAPP was similar between groups. However, after ileostomy closure, the complication rate was significantly reduced with the use of loop ileostomy. We conclude that loop ileostomy is a desirable option for UC patients undergoing intestinal diversion during IAPP. Loop ileostomies can be created easily and without an increase in operative time. Subsequent ileostomy closure can be performed as a local procedure, which may shorten operative time and length of hospital stay.

Adolescent↗
PubMed1997

Interleukin-10 prevents early cytokine release in severe intraabdominal infection and sepsis.

Early release of macrophage-derived proinflammatory cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, are important in the pathogenesis of septic shock and multisystem organ failure in various models of sepsis. IL-10 is a mediator that inhibits cytokine release from activated macrophages. The aim of this study was to determine if IL-10 would decrease serum cytokine elevation in a murine model of cecal ligation and puncture (CLP). CLP in animals is a model that closely mimics the physiologic changes seen in human sepsis. Four groups of 14 female Swiss-Webster mice were used. Group 1 underwent laparotomy alone, groups 2, 3, and 4 underwent laparotomy and CLP. Groups 1 and 2 received intraperitoneal (IP) saline injections to serve as control vehicle. Group 3 (prophylactic) received 10,000 U IP IL-10 1 hr prior to CLP and every 3 hr thereafter. Group 4 (therapeutic) received 10,000 U IP IL-10 1 hr following CLP and every 3 hr thereafter. Animals were sacrificed at 3 and 9 hr following CLP. Serum TNF-alpha, IL-1 beta, and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA), CLP produced a significant rise in serum TNF,IL-6, and IL-1 in untreated controls. Prophylactic or therapeutic administration of IL-10 significantly attenuated this early rise in serum cytokines. These results support the hypothesis that (1) CLP produces an early systemic rise in macrophage-derived cytokines and (2) IL-10 given either before or after the onset of CLP-induced intraabdominal infection and sepsis is able to inhibit this early release of macrophage-derived systemic mediators. IL-10 has potential clinical benefits in the therapeutic management of intraabdominal infection and sepsis.

Abdomen, Acute↗
PubMed1997

Epidermal growth factor selectively enhances functional enterocyte adaptation after massive small bowel resection.

After massive small bowel resection, the intestine adapts to compensate. In addition to proliferation, enterocytes also undergo selective functional adaptation. In this study we examined the effect of intraperitoneal administration of epidermal growth factor (EGF) on the expression of the brush border dissacharidase sucrase, the sodium glucose cotransporter (SGLT1), and the sodium-potassium ATPase pump (NaK ATPase) by enterocytes in the remnant intestine after massive small bowel resection. Adult Lewis rats underwent either ileal transection or 70% proximal intestinal resection. These animals were subdivided into groups that received either saline or EGF intraperitoneally for 1 week. Ilea from each group were harvested 4 weeks postoperatively. Enterocytes were separated from these segments by calcium chelation. The total protein from the isolated cells was subjected to Western blot analysis. Administration of EGF to animals that underwent transection did not significantly alter the expression of sucrase, SGLT1, or NaK ATPase. After intestinal resection, the expressions of sucrase and SGLT1 were significantly increased. The combination of EGF administration and intestinal resection resulted in a further increase in SGLT1 expression. The intraperitoneal administration of EGF selectively enhanced the expression of SGLT1 by enterocytes after massive small bowel resection. Administration of EGF to sham-operated animals did not have similar effects. These results suggest that EGF augments the adaptive response and may therefore have a therapeutic role in the management of patients with short bowel syndrome.

Adaptation, Physiological↗
PubMed1997

Intraluminal peptide YY induces colonic absorption in vivo.

INTRODUCTION: Peptide YY (PYY) is a 36 amino acid hormone released into the circulation and lumen of the intestine after a meal. Previous studies have shown that exogenous administration of intravenous PYY stimulates water and electrolyte absorption in both the small and large intestines. The purpose of this study was to examine the effects of intraluminal administration of PYY on colonic absorption of electrolytes and water. METHODS: Six conditioned 25-kg dogs had 20 cm of colonic Thiry-Vella fistulae surgically constructed under general anesthesia. After a two-week recovery period, the animals received intraluminal PYY at 600 pmol/kg/hour after a 90-minute steady-state basal period. The Thiry-Vella fistulae were perfused with an isotonic buffer solution containing [14C]polyethylene glycol as a volume marker. Ion and water transport were measured every 15 minutes. RESULTS: On intraluminal infusion of PYY, increased absorption of water, sodium, and chloride was observed in the colon. A twofold increase in absorption rates occurred compared with basal rates lasting more than one hour after cessation of intraluminal PYY (N = 6; P < 0.05 vs. basal by analysis of variance). CONCLUSION: PYY-secreting cells of the colon may contribute to the regulation of absorption after a meal. Exogenous administration of intraluminal PYY may also be a therapeutic treatment modality for malabsorption.

Animals↗
PubMed1997

Interleukin-10 reduces the systemic inflammatory response in a murine model of intestinal ischemia/reperfusion.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in distant organs. This study was designed to investigate the effect of interleukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulation, and histologic changes in a murine model of I/R. METHODS: Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours, starting 1 hour before reperfusion (Pretreatment). Group 4 was treated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays were performed for serum cytokine levels, and lung myeloperoxidase activity and intestinal histology were scored. RESULTS: Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before or after reperfusion. CONCLUSIONS: IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when given before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distant organ neutrophil accumulation.

Animals↗
PubMed1997

An ETa/ETb endothelin antagonist ameliorates systemic inflammation in a murine model of acute hemorrhagic pancreatitis.

BACKGROUND: Endothelin peptides are polykines with strong vasoconstrictor properties. We have previously shown that endothelin antagonism (PD145065) reduces the local severity of acute pancreatitis. We now investigated the effect of endothelin antagonism on systemic inflammation in a model of acute hemorrhagic pancreatitis. METHODS: Forty-two mice were divided into four groups. Group 1 was fed standard food plus PD145065 every 8 hours. Group 2 was fed a choline-deficient ethionine (CDE) supplemented diet and given saline every 8 hours. Group 3 was fed a CDE diet and treated with PD145065 every 8 hours from initiation of diet. Group 4 was fed a CDE diet and given PD145065 from 48 hours after initiation of diet. Animals were killed at 70 hours. Serum was collected. Pancreata and lung tissue were harvested. RESULTS: Histology score, serum amylase level, lung myeloperoxidase, and interleukin (IL)-10 were all significantly reduced in both treatment groups (groups 3 and 4) (p < 0.05). IL-6 levels were reduced in group 3 only (p < 0.05). The mortality rate did not differ among any of the groups. CONCLUSIONS: Endothelin antagonism decreased the severity of acute pancreatitis and reduced markers of systemic inflammation. Late treatment at 48 hours failed to prevent the rise in IL-6. Mortality rates were unaffected by treatment.

Acute Disease↗
PubMed1997

Antisecretory mechanisms of peptide YY in rat distal colon.

Peptide YY (PYY) is a potent regulator of intestinal secretion. These studies investigated the role of Y1 and Y2 receptor subtypes in mediating the antisecretory effects of PYY on mucosa-submucosa preparations of rat distal colon. Addition of vasoactive intestinal peptide (VIP) to these tissues resulted in a 140 +/- 18% increase in basal short-circuit current (Isc) and the induction of Cl- secretion. VIP-stimulated increases in Isc were abolished by the addition of each of PYY, (Pro34)-PYY, a Y1 receptor-selective agonist, and PYY-(3-36), an endogenous Y2 receptor-selective ligand. However, when tissue neural transmission was blocked with tetrodotoxin, neither PYY nor its receptor subtype-selective analogs were able to inhibit VIP-stimulated increases in Isc. These results suggest that in the rat distal colon, the antisecretory actions of PYY are mediated through a combination of Y1 and Y2 receptor subtypes or through a novel receptor subtype that is unable to discriminate between (Pro34)-PYY and PYY-(3-36).

Animals↗
PubMed1997

Jejunal lymphangioma. An unusual cause of chronic gastrointestinal bleeding.

We discuss a case of lymphangioma of the small bowel that caused chronic anemia secondary to gastrointestinal blood loss. We believe that this is the first jejunal lymphangioma to be diagnosed by Sonde endoscopy. There are several other lymphatic abnormalities of the small intestine that are briefly discussed. In the Western literature, anemia or chronic gastrointestinal blood loss is an unusual presentation of lymphangioma of the small bowel.

Adult↗
PubMed1997

Interleukin 10 reduces the severity of acute pancreatitis in rats.

BACKGROUND & AIMS: Previous studies have documented the effectiveness of interleukin (IL)-10 if given before the onset of experimental acute pancreatitis. This study examined whether IL-10, a cytokine that inhibits macrophage release of inflammatory mediators, would alter the severity of acute pancreatitis if given before or after the induction of disease. METHODS: Eighty-four Sprague-Dawley rats were divided into four groups. Group 1 received intravenous saline, and groups 2, 3, and 4 received intravenous cerulein (8.5 microg x kg(-1) x h(-1)). Group 3 was also given 150,000 U of intraperitoneal IL-10 1 hour before cerulein infusion and every 3 hours thereafter. Group 4 received 150,000 U intraperitoneal IL-10 2 hours after cerulein infusion and every 3 hours thereafter. Serum amylase and tumor necrosis factor (TNF)-alpha levels were measured before and 3, 9, or 15 hours after induction of pancreatitis. Animals were killed at these time points. Pancreata were analyzed for edema and TNF-alpha mRNA and TNF-alpha protein concentrations and were graded histologically. RESULTS: Serum amylase, TNF-alpha mRNA, and TNF-alpha protein levels, pancreatic edema, and histological score were significantly reduced when IL-10 was administered either before or after induction of pancreatitis. Serum TNF-alpha levels were undetectable. CONCLUSIONS: IL-10 attenuated the severity of experimental acute pancreatitis if given either before or after the induction of the disease. These results are consistent with the hypothesis that the macrophage is important in determining the severity of acute pancreatitis in this model.

Acute Disease↗
PubMed1997

Effect of ethanol on pancreatic interstitial pH and blood flow in cats with chronic pancreatitis.

OBJECTIVE: The objective of this study was to investigate the effects of ethanol on pancreatic blood flow and interstitial pH in chronic pancreatitis. BACKGROUND: Ethanol is known to contribute to the development of both acute and chronic pancreatitis. However, it is unclear how ethanol precipitates episodes of acute pancreatic inflammation in the setting of chronic pancreatitis. In a model of chronic pancreatitis in cats, it is known that pancreatic blood flow is abnormally low and decreases further after ethanol ingestion. Because it is possible that this reduction in blood flow might be damaging to the pancreas, we investigated the effects of ethanol on pancreatic interstitial pH, an index of pancreatic ischemia. METHODS: In normal cats and cats with obstructive chronic pancreatitis, pancreatic blood flow and interstitial pH were measured using the hydrogen gas clearance technique and pH microelectrode, respectively. RESULTS: In normal cats, intragastric, but not intravenous, ethanol reduced both pancreatic blood flow by 62% (p < 0.05) and interstitial pH (7.38 +/- 0.03 to 7.20 +/- 0.03, p < 0.05). In cats with chronic pancreatitis in which basal pancreatic blood flow was already only 60% of normal flow, both intragastric and intravenous ethanol decreased both pancreatic blood flow (intragastric, 40% decrease, p < 0.05; intravenous, 34% decrease, p < 0.05) and interstitial pH (intragastric, 7.24 +/- 0.04 to 7.08 +/- 0.04, p < 0.05; intravenous 7.20 +/- 0.08 to 7.07 +/- 0.07, p < 0.05). CONCLUSIONS: This profound decrease in pH, lasting up to 2 hours after ethanol exposure in the chronic pancreatitis animals, suggests the possibility of ischemic cellular damage to the pancreas. These findings may explain the pathogenesis of bouts of acute pancreatic inflammation after ethanol ingestion in the setting of chronic disease.

Animals↗