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Biomedical subjects

J J Cullen

Publications and source records attributed to J J Cullen.

At least 55 records · Page 3Linked to original sources
PubMed1994

Gastrointestinal peptide hormones during postoperative ileus. Effect of octreotide.

The hypothesis was that postoperative ileus might be caused by a disturbed balance between the motor-stimulating hormones, motilin and substance P, and the motor-inhibitory hormone, vasoactive intestinal polypeptide, and that octreotide might prevent this disturbance and so ameliorate the ileus. In 15 conscious dogs with chronic gastrointestinal electrodes, electrical activity was recorded and blood was drawn for radioimmunoassay of motilin, substance P, and vasoactive intestinal peptide (VIP) during fasting and after a liquid meal. Ileus was then induced by celiotomy and intestinal abrasion. During and after operation, five dogs received 154 mM NaCl only, five dogs octreotide, 0.19 micrograms/kg/hr, and five octreotide, 0.83 micrograms/kg/hr. Plasma levels of motilin, substance P, and VIP were changed little by operation, but cyclical increases in plasma motilin, which occurred preoperatively during phase III of the interdigestive myoelectric complex, were completely abolished postoperatively during ileus, as was the complex itself. Octreotide ameliorated the ileus and restored the cyclic increases in motilin found in health, nor did it alter plasma substance P and VIP. In conclusion, octreotide ameliorates postoperative ileus, but it does not do so by increasing plasma motilin or substance P or decreasing plasma VIP.

Animals↗
PubMed1994

Prospectively evaluating anal sphincter function after ileal pouch-anal canal anastomosis.

The decreased anal sphincter pressure that occurs after ileal pouch-anal canal anastomosis (IPAA) has usually been attributed to damage of the internal and sphincter. We hypothesized that the operation damages both the internal and the external anal sphincter. Resting pressure in the anal canal (a function of internal and external sphincters), anal squeeze pressure (a function of external sphincter only), and the rectal-anal inhibitory reflex (involving the internal sphincter) were measured manometrically in 10 patients with ulcerative colitis (4 women and 6 men; mean age, 33 years; range: 20 to 49 years). The patients were studied while awake before IPAA, under general anesthesia with striated muscle blockade just before incision, awake 2 months later before ileostomy takedown, and again under anesthesia with blockade just before takedown. The operation decreased maximum resting anal pressure while awake and during anesthesia with blockade. The decrease was detected in the proximal anal canal but not in the distal anal canal. In addition, the operation impaired anal squeeze pressure and abolished the rectal-anal inhibitory reflex. We conclude that IPAA damages both the internal and the external anal sphincter.

Adult↗
PubMed1994

Pancreatic anastomotic leak after pancreaticoduodenectomy: incidence, significance, and management.

Anastomotic leak at the pancreaticojejunostomy remains a common and dreaded complication after pancreaticoduodenectomy. Our aim was to determine the incidence, presentation, methods of management, and preoperative and postoperative factors that influence the clinical outcome. We reviewed our collective experience with 375 consecutive patients undergoing pancreaticoduodenectomy from 1980 to 1992 for a variety of pathologic indications. Clinical, biochemical, intraoperative, and postoperative factors were reviewed in an attempt to determine prognostic factors. Sixty-six patients (18%) developed a pancreatic anastomotic leak as determined by increased amylase in drainage fluid (44%), radiographic documentation (41%), operative re-exploration (9%), or percutaneous drainage of a peripancreatic, amylase-containing fluid collection (6%). Most leaks (73%) were clinically insignificant and were managed by simple maintenance of intraoperatively placed drains. Active intervention was required in 18 patients (27%) and included percutaneous drainage in 8, completion pancreatectomy in 7, and reoperative drainage with or without anastomotic repair in 3. Although octreotide was used therapeutically in 13 patients (20%), a significant, objective response was noted in only 1 patient. Five (8%) of the 66 patients died, all related directly to the pancreatic leak. The overall operative mortality was lower, 15 (4%) of 375 patients. Of the clinical, biochemical, intraoperative, and postoperative factors reviewed to determine prognostic factors, only postoperative intra-abdominal hemorrhage predisposed the patient to mortality as a result of the pancreatic anastomotic leak. We conclude that most anastomotic leaks at the pancreaticojejunostomy after pancreaticoduodenectomy can be managed conservatively. Use of octreotide to aid in closure of the pancreatic leak was disappointing, whereas patients with postoperative intra-abdominal hemorrhage or those requiring completion pancreatectomy to manage the anastomotic leak have increased mortality.

Adult↗
PubMed1994

Surgical management of Meckel's diverticulum. An epidemiologic, population-based study.

OBJECTIVE: The authors determined whether Meckel's diverticulum, discovered incidentally at operation, should be removed. SUMMARY BACKGROUND DATA: It is not clear from the medical literature whether the risk of an incidental Meckel's diverticulectomy is greater than the risk of leaving the diverticulum in place. METHODS: The authors used the medical experience of Olmsted County, Minnesota residents for the period 1950 to 1992 to answer the question. RESULTS: During the period, 58 residents developed Meckel's complications that required diverticulectomies. The incidence of complications was 87 per 100,000 person-years, and the lifetime risk (to 80 years of age) of developing them was 6.4%. The risks were similar throughout the period and at all ages of life, but were greater among men (124 per 100,000 person-years) than women (50 per 100,000 person-years, p < 0.05). Diverticulectomies for complications carried an operative mortality and morbidity of 2% and 12% and a cumulative risk of long-term postoperative complications of 7%, whereas incidental diverticulectomies done in 87 residents during the period carried corresponding rates of only 1%, 2%, and 2%, respectively. CONCLUSIONS: Meckel's diverticula discovered incidentally at operation should be removed for most patients, regardless of age.

Adolescent↗
PubMed1994

Captopril decreases stress ulceration without affecting gastric perfusion during canine hemorrhagic shock.

The renin-angiotensin axis has recently been called the source of disproportionate splanchnic vasoconstriction during shock, and blocking this axis decreased gastric stress ulceration during swine cardiogenic shock. The present study tested whether the angiotensin converting enzyme inhibitor captopril would prevent stress ulceration when given after the onset of canine hemorrhagic shock, and whether any detrimental effects would result from enhancing splanchnic perfusion with captopril during hemorrhagic shock. We found that captopril treatment was associated with a decrease in gastric mucosal injury and with a marked decrease in systemic acidosis. Captopril enhanced blood flow to the small intestine, pancreas, liver, and spleen, but not flow to the stomach, during shock. Following the reinfusion of shed blood, the captopril-treated animals had decreased mean blood pressures and increased heart rates compared with untreated animals. We found captopril alleviated the stress ulceration produced by canine hemorrhagic shock, but concluded that the likely mechanism was alleviating systemic acidosis through enhanced perfusion of other viscera rather than a specific enhancement of gastric perfusion.

Analysis of Variance↗
PubMed1994

Influence of proximal gastric vagotomy on canine gastric motility and emptying.

BACKGROUND: The aim was to determine the effect of proximal gastric vagotomy on proximal gastric tone, distal gastric motility, and gastric emptying in seven conscious dogs. METHODS AND RESULTS: Before vagotomy, insulin (1 unit/kg intravenously) caused a prompt decrease in proximal gastric tone measured with a barostat and a marked increase in distal gastric motility measured with a perfused, pressure-sensitive catheter, both of which were maximal at 30 minutes. Proximal gastric tone then returned to the control level during the ensuing 30 minutes, whereas the increase in distal gastric motility continued. Gastric emptying of an inert marker, polyethylene glycol, was unchanged by insulin. After vagotomy, insulin again caused a prompt decrease in proximal gastric tone, an increase in distal gastric motility, and no change in gastric emptying of marker, but the decrease in proximal gastric tone now persisted for the entire hour after administration of insulin. CONCLUSIONS: Relaxation of the proximal stomach is mediated by pathways not solely dependent on the proximal gastric vagal nerves, but the ability to regain proximal gastric tone is impaired by proximal vagotomy. In contrast, vagal drive to distal gastric motility and gastric antral emptying are preserved after proximal gastric vagotomy.

Animals↗
PubMed1994

The future of intestinal pacing.

Pacing the human heart, first done in 1952, is commonly used today. Pacing the canine stomach and small intestine has also been accomplished and has been used to treat a variety of disease models, including dumping, the short bowel syndrome, gastroparesis, the Roux stasis syndrome, and tachygastria. In contrast, pacing the human stomach and small intestine has not progressed as far. Pacing of these organs in man has only been done for short intervals. Moreover, no clear-cut therapeutic applications have as yet emerged. Nonetheless, pacing holds promise as a future therapeutic modality for a variety of disorders of the human stomach and small bowel.

Animals↗
PubMed1993

Treatment of acute postoperative ileus with octreotide.

Our hypothesis was that postoperative ileus is caused by the release of neurotransmitters in the gut wall that inhibit motility. We reasoned that blocking the release with octreotide would prevent ileus. We placed serosal electrodes on the small intestine and stomachs of 15 dogs and inserted a duodenal cannula. After the animals recovered, electrical activity was recorded, and small bowel transit, colonic transit, and gastric emptying were studied radiographically and scintigraphically. Ileus was induced by celiotomy and intestinal abrasion. Dogs were randomized to receive on postoperative days 0 through 3 either a placebo (n = 5), octreotide, 1.5 micrograms/kg/8 hr subcutaneously (n = 5), or octreotide 0.83 micrograms/kg/hr intravenously (n = 5). Both doses of octreotide resulted in a faster return to preoperative values of small bowel interdigestive myoelectric activity and transit and colonic transit than did the placebo. The larger dose of octreotide, however, slowed gastric emptying. In conclusion, octreotide shortened the duration of postoperative ileus in the small bowel and colon of dogs.

Animals↗
PubMed1993

Gastric motor physiology and pathophysiology.

The stomach has two distinct physiologic motor areas: the proximal stomach and the distal stomach. The proximal stomach, with its slow, sustained contractions, has a key role in regulating intragastric pressure and gastric emptying of liquids, while the distal stomach, with its peristaltic contractions, has a major role in mixing, trituration, and emptying of solids. Diseases and operations that disturb the motility of these two areas can result in unique adverse motor sequelae. For example, operations that impair proximal gastric motility, such as proximal gastric resection, may cause rapid gastric emptying of liquids and subsequent dumping and diarrhea. In contrast, operations that impair distal gastric contractions, such as truncal vagotomy, may cause slow gastric emptying of solids and chronic gastric atony. Knowledge of the physiology of the stomach in health and of the pathophysiology with disease and after operation provides a basis for the successful treatment and prevention of these disorders.

Animals↗
PubMed1987

Regulation of sodium absorption by canine tracheal epithelium.

To regulate the quantity of respiratory tract fluid, the airway epithelium either secretes chloride, Cl-, or reabsorbs sodium, Na+. Many secretagogues inhibit Na+ absorption, but the decrease may result from a fall in the electrochemical gradient for Na+ absorption. We examined regulation of Na+ absorption independent of Cl- secretion, by bathing canine tracheal epithelium in Cl--free, gluconate Ringers solution. Prostaglandin E2, 2-chloroadenosine, and isoproterenol increased short-circuit current (Isc) and the rate of Na+ absorption. In contrast, indomethacin, which inhibits endogenous prostaglandin production, decreased Isc. These agents regulate cellular levels of cAMP; direct addition of 8-Br-cAMP also acutely increased Isc. We examined chronic regulation of Na+ absorption in cell monolayers grown on permeable supports in serum-free media. Exposure to aldosterone for two days increased baseline Isc by 50% and the amiloride-inhibitable current by 55%. These data indicate that Na+ absorption is both acutely and chronically regulated in the airway epithelium.

2-Chloroadenosine↗
PubMed1986

The effects of high-nutrient urea on in vitro bullfrog fundic mucosa.

The effects of nutrient urea (240 mM) on H+ secretion, potential difference, and resistance were studied in isolated sheets of bullfrog fundic mucosa. H+ secretion was significantly reduced while transmucosal resistance was significantly increased and potential difference was significantly decreased. Measurement of CO2 utilization by, and distribution across, the mucosal sheets demonstrated that oxidative metabolism is increased (tCO2, 4.93 +/- 0.2 to 5.83 +/- 0.3 mumole/cm2 hr-1, P less than 0.05) and that generation of protons (H+) within the oxyntic cell is stimulated (delta CO2, 1.48 +/- 0.1 to 2.22 +/- 0.2 mumole/cm2 hr-1, P less than 0.05, and nutrient HCO-3 1.35 +/- 0.2 to 2.21 +/- 0.2 mueq/cm2 hr-1, P less than 0.05) in spite of paradoxically diminished H+ appearance on the secretory surface. Studies using 120 and 60 mM urea suggest that the effects may be dose dependent. Results with 240 mM sucrose on the nutrient surface would indicate that those seen with urea cannot be attributed entirely to the hyperosmolality. Pretreatment of the mucosal sheets with metiamide (10(-3) M) resulted in the expected decrease in titratable H+ (to 0) but had no effect on urea-stimulated oxidative metabolism (tCO2, 2.09 +/- 0.2 to 2.91 +/- 0.4 mumole/cm2 hr-1, P less than 0.02) or the generation of protons by the oxyntic cell (delta CO2, 0.68 +/- 0.1 to 1.35 +/- 0.3 mumole/cm2 hr-1, P less than 0.02, and nutrient HCO3- 0.83 +/- 0.1 to 1.65 +/- 0.3 mueq/cm2 hr-1, P less than 0.05). Both simultaneous or subsequent treatment with theophylline (5 X 10(-3) M) reversed the inhibitory effect of urea on H+ secretion. Transmission electron microscopy revealed involution of the secretory membrane following treatment with urea but maintenance of the microvillous secreting configuration of the membrane when theophylline was added to the nutrient solution. These results suggest that although nutrient urea stimulates the generation of H+ within the cell it simultaneously inhibits release of H+ by the secretory membrane. Failure to inhibit urea-stimulated generation of H+ within the cell by metiamide indicates that the increased oxidative metabolism and generation of protons stimulated by nutrient urea is probably not histamine-mediated. It is suggested that urea inhibits adenylyl cyclase and thus cAMP-mediated evolution of the secretory membrane with reduced H+ transport, an effect that can be reversed by inhibiting phosphodiesterase with theophylline.

Animals↗
PubMed1986

Paracellular back-diffusion of H+ across bullfrog fundic mucosa resulting from Ca2+ depletion and its effects on taurocholate-induced mucosal injury.

The effects of calcium depletion (by washout and by chelation with EDTA) on the net appearance of hydrogen ions (H+) on the secretory surface of in vitro sheets of bullfrog fundic mucosa have been studied. A CO2 distribution method was used to distinguish between true and apparent inhibition of H+ secretion. Our data indicate that Ca2+ depletion produces apparent inhibition of H+ secretion by increasing paracellular back-diffusion of H+ across the mucosa. Ca2+ washout resulted in a decrement of measurable H+ (1.42 +/- 0.07 to 0.93 +/- 0.09 muEq/cm2 hr-1, P less than 0.05) without altering delta CO2 (1.18 +/- 0.15 to 1.26 +/- 0.17 muEq/cm2 hr-1, not significant). Chelation of Ca2+ with EDTA produced a similar decrease in H+ (1.61 +/- 0.09 to 0.78 +/- 0.12 muEq/cm2 hr-1, P less than 0.05) without affecting delta CO2 (1.60 +/- 0.13 to 1.68 +/- 0.22 muEq/cm2 hr-1, not significant). The possibility that H+ back-diffusion (induced by Ca2+ depletion) via a paracellular shunt might ameliorate injury was examined in bullfrog fundic mucosa exposed to a bile salt. H+ secretion, potential difference, resistance, and ultrastructural changes were studied in isolated mucosal sheets treated with 10 mM sodium taurocholate with or without Ca2+ depletion. Measurable H+, potential difference, and resistance were significantly lower in the Ca2+ depleted tissues. Scanning electron microscopy revealed identical changes in the surface epithelial cells of both depleted and nondepleted mucosae, but there was significantly less cell loss from depleted mucosae (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Standard Roux-en-Y gastrojejunostomy vs. "uncut" Roux-en-Y gastrojejunostomy: a matched cohort study.

Roux-en-Y gastrojejunostomy is a common method of reconstruction after subtotal gastrectomy. Maintaining myoneural continuity has been proposed to decrease the incidence of Roux stasis syndrome, with an "uncut" Roux-en-Y reconstruction. The aim of our study was to compare the clinical results in patients who have undergone uncut Roux-en-Y gastrojejunostomy with those in patients who have undergone a standard Roux-en-Y gastrojejunostomy. Eleven patients underwent gastrectomy and uncut Roux-en-Y gastrojejunostomy and were compared with a cohort of 14 patients who underwent gastrectomy and standard Roux-en-Y gastrojejunostomy. Patients were contacted and charts were reviewed for Visick grade, early and late morbidity and mortality, and incidence of staple line dehiscence. Early postoperative morbidity was 18% in patients undergoing uncut Roux gastrojejunostomy and 28% in patients undergoing standard Roux reconstruction. There were no early postoperative deaths in either group. In the patients undergoing the uncut Roux procedure, no cases of staple line dehiscence were detected clinically (mean follow-up 9 months, range 1 to 48 months). Visick grade improved following the uncut Roux procedure, but changed little after standard Roux reconstruction. Uncut Roux-en-Y gastrojejunostomy can be performed safely with improvement in symptoms. The uncut Roux procedure may provide an alternative for reconstructive gastric surgery.

Adult↗
PubMedDate not supplied

Endotoxin temporarily impairs canine jejunal absorption of water, electrolytes, and glucose.

Enteral feeding during and after episodes of sepsis may be beneficial. The aim of our study was to determine the effects of a single sublethal dose of endotoxin on canine jejunal absorption. Following a 240 kcal liquid meal, absorption studies were performed in eight dogs with 75 cm jejunal Thiry-Vella fistulas. These fistulas were perfused with an isotonic solution containing polyethylene glycol to calculate absorption. Each dog was then given a single dose of Escherichia coli lipopolysaccharide, 200 microg/kg intravenously, and the studies were repeated for the next 3 days. Following endotoxin bolus infusion, net absorption of water, electrolytes, and glucose was decreased for 2 days and returned to baseline values on postendotoxin day 3. A single sublethal dose of endotoxin temporarily impairs canine jejunal absorption. Although enteral feeding may be advantageous, jejunal absorption may be temporarily impaired following an episode of endotoxemia.

Animals↗
PubMedDate not supplied

Effect of endotoxin on canine colonic motility and transit.

Diarrhea is a common problem in patients who have episodes of sepsis and are being fed enterally. Endotoxemia results in gastrointestinal motor dysfunction characterized by slowed gastric emptying and rapid intestinal transit; however, the effect of endotoxin on colonic motility is unknown. The aim of our study was to determine the effects of a single sublethal dose of endotoxin on colonic motility and transit. Seven dogs underwent construction of a 50 cm colonic Thiry-Vella fistula. Five manometry catheters were sewn into the colonic lumen at 8 cm intervals along the fistula. Following recovery, the fistula was perfused with an isotonic solution at 2.9 ml/min, and fasting and postprandial colonic motility was determined. Liquid transit was assessed by bolus of a nonabsorbable marker instilled into the proximal end of the Thiry-Vella fistula. Recordings of gastrointestinal contractile activity were made digitally to determine contractile frequencies and motility indexes. Following completion of the baseline studies, each dog was given a single dose of E. coli lipopolysaccharide, 200 microgram/kg intravenously, and studies were repeated daily for the next 3 days. Endotoxin doubled the fasting colonic contractile frequency on postendotoxin day 1 and also increased motility indexes on that same day. Fasting motility indexes and contractile activity were decreased on postendotoxin days 2 and 3. The postprandial frequency of contractions and motility indexes were decreased on postendotoxin day 3. Fasting colonic liquid transit was rapid on postendotoxin day 1, whereas postprandial liquid transit was rapid on both postendotoxin days 1 and 2. Endotoxin temporarily speeds liquid transit and increases both the frequency and strength of colonic contractions. These effects may contribute to the diarrhea that occurs during episodes of sepsis.

Animals↗