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Biomedical subjects

M G Sarr

Publications and source records attributed to M G Sarr.

At least 145 records · Page 8Linked to original sources

Effect of a model of canine jejunoileal orthotopic autotransplantation on jejunal and ileal transport of water and electrolytes.

Canine jejunoileal transplantation induces an early profuse watery diarrhea of uncertain etiology. Our aim was to determine the temporal effects of a canine model of jejunoileal autotransplantation (a model devoid of confounding effects of ischemia-reperfusion or immune rejection) on basal jejunal and ileal absorption of water and electrolytes to determine if impaired absorption is responsible for the diarrhea. Our hypothesis was that net absorption of water and electrolytes in an enterically isolated loop would decrease after jejunoileal transplantation. Four groups of dogs (N > or = 6) were prepared with 80-cm modified Thiry-Vella loops: group I, neurally intact jejunum; group II, autotransplanted jejunum; group III, neurally intact ileum; and group IV, autotransplanted ileum. The loops were perfused for 3 hr with 150 mM NaCl at 3 ml/min under fasted conditions; transit time through the loop was determined by bolus of a nonabsorbable marker. Dogs were studied on three separate days at one, two, eight, and nine weeks postoperatively. Net absorptive fluxes of water and electrolytes and transit times were similar (P > 0.05) between neurally intact and autotransplant groups (group I vs II and group III vs IV) at each time point. Ileal loops absorbed more than jejunal loops, and transit was slower in ileal loops (each P < 0.05). Our findings suggest that, despite the obligate disruption of extrinsic innervation, enteric (intrinsic) neural continuity, and lymphatic drainage that accompanies this canine model of jejunoileal autotransplantation, net basal absorptive function of water and electrolytes during the fasted state was not decreased nor was transit altered either in jejunum or ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Duodenal nutrients inhibit canine jejunal fasting motor patterns through a hormonal mechanism.

Ingestion of a meal converts the fasting motor pattern, the migrating motor complex (MMC), to a fed pattern of motility. The role of specific anatomic gut regions involved in these changing patterns of motility and the neurohormonal factors which mediate these changes, however, are unknown. Our aim was to determine the neurohormonal mechanisms by which nutrients within the duodenal lumen alter proximal jejunal motility. Fifteen dogs were prepared with a gastric cannula, duodenal infusion catheter, duodenal and proximal jejunal manometry catheters, and a totally diverting cannula in the most proximal portion of the jejunum. Ten of the dogs also underwent complete in situ neural isolation of the entire jejunoileum. Experiments were performed in the fasting state with no infusion (0 ml/min) and during a 5-hr duodenal infusion (3 ml/min) of either a nonnutrient electrolyte solution or a mixed nutrient solution while diverting distal duodenal chyme from the jejunum. During sham infusion (0 ml/min), the MMC was present in neurally intact dogs (group 1) and dogs with neurally isolated jejunoileum (group 2). Nonnutrient infusion did not inhibit or consistently alter the MMC in either group. Nutrient infusion limited to the duodenum inhibited the MMC in both duodenum and jejunum in dogs with neurally intact and neurally isolated jejunoileum. Latency of onset of the fed pattern in the duodenum and jejunum did not differ between groups. We conclude that postprandial inhibition of the MMC in the jejunum is mediated, in part, by a hormonal mechanism induced by duodenal lumenal nutrients.

Animals↗

Prospective evaluation of gastric acid secretion and cobalamin absorption following gastric bypass for clinically severe obesity.

The pathophysiologic mechanism(s) responsible for cobalamin deficiency after Roux-en-Y gastric bypass for clinically severe obesity remains unexplained. Inadequate secretion of intrinsic factor has been postulated, but decreased gastric acid secretion resulting in maldigestion and inadequate liberation of free cobalamin from its native protein-bound form is also possible. The aim of this study was to determine prospectively secretion of gastric acid and absorption of crystalline (free) and protein-bound cobalamin before and after gastric bypass. Eight patients (two men, six women) underwent orogastric intubation of the intact stomach preoperatively and the proximal gastric pouch postoperatively. Gastric acid secretion in the basal and stimulated (pentagastrin, 6 micrograms/kg) states was determined by a perfused, nonabsorbable marker technique to quantitate recovery of gastric secretion. Absorption of radiolabeled (57Co) crystalline and protein-bound cobalamin was assessed on separate days by 24-hr urinary excretion. After gastric bypass, acid secretion (mean +/- SEM) was markedly reduced in basal (9.1 +/- 3.6 vs 0.005 +/- 0.003 meq/hr; P = 0.04) and stimulated (12.8 +/- 1.8 vs 0.008 +/- 0.003 meq/30 min; P = 0.002) states. Absorption of crystalline cobalamin was decreased (15.8 +/- 2.5 vs 9.4 +/- 1.4%; P = 0.08) to a lesser extent than was protein-bound cobalamin (5.9 +/- 1.0 vs 1.1 +/- 0.3%; P = 0.004). In summary, gastric acid secretion from the gastric pouch is negligible after gastric bypass, and food-bound cobalamin is maldigested and subsequently malabsorbed presumably due to pouch achlorhydria. Decreased absorption of free cobalamin suggests decreased cobalamin-intrinsic factor complex formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

Mesenteric venous thrombosis: still a lethal disease in the 1990s.

PURPOSE: This study was designed to evaluate progress in diagnosis, management, and clinical outcome of mesenteric venous thrombosis (MVT). METHODS: We retrospectively reviewed the clinical course of 72 patients treated for mesenteric venous thrombosis between 1972 and 1993. RESULTS: Fifty-three patients had acute and 19 had chronic mesenteric venous thrombosis. Fifty-seven patients had secondary mesenteric venous thrombosis; previous abdominal surgical procedure and hypercoagulable states were the most prevalent associated conditions. Computed tomography was abnormal in all patients who underwent this test for acute mesenteric venous thrombosis and in 93% of those who had chronic disease. Angiography diagnosed acute mesenteric venous thrombosis in five (72%) of seven patients. Acute mesenteric venous thrombosis presented most frequently as abdominal pain (83%), anorexia (53%), and diarrhea (43%). Thirty-three (75%) had symptoms longer than 48 hours. Thirty-four (64%) patients with acute mesenteric venous thrombosis underwent a surgical procedure. Bowel resection was necessary in 31 patients. One patient had unsuccessful mesenteric venous thrombectomy. Seven patients with acute mesenteric venous thrombosis underwent anticoagulation without a surgical procedure, and 12 were observed. All patients with chronic mesenteric venous thrombosis were observed; nine of the 19 underwent anticoagulation. The median delay in diagnosis for patients with acute mesenteric venous thrombosis was 48 hours and did not decrease during the last decade. Mesenteric venous thrombosis recurred in 19 (36%) patients. The 30-day mortality was 27%. Long-term survival of patients with acute mesenteric venous thrombosis was significantly worse than that of those with chronic disease (36% vs 83% survival at 3 years). The patients with acute mesenteric venous thrombosis who underwent anticoagulation with and without surgical procedure had improved survival when compared with the observed group. CONCLUSION: Acute mesenteric venous thrombosis remains a lethal disease. Mortality has not improved in the last 22 years. Computed tomography is the most sensitive diagnostic test. Anticoagulation and surgical procedure enhanced survival in the acute subgroup. The underlying disease determined survival in chronic disease.

Acute Disease↗

The natural history of surgically treated primary adenocarcinoma of the appendix.

OBJECTIVE: The aim of this investigation was to determine the prognostic variables and optimal surgical procedure for patients with adenocarcinoma of the appendix. SUMMARY BACKGROUND DATA: Primary adenocarcinoma of the appendix is a rare malignancy that constitutes less than 0.5% of all gastrointestinal neoplasms. However, the prognostic factors and the preferred surgical procedure and outcome are poorly understood. METHODS: The authors reviewed their institutional experience from 1976 to 1992 in treating 94 consecutive patients with primary adenocarcinoma of the appendix. Patients with carcinoid tumors or those in whom the diagnosis of primary cecal cancer could not be ruled out were excluded from the study. RESULTS: Fifty-two (55%) patients had the mucinous variety, of which 22 had pseudomyxoma peritonei; the other 45% had the colonic and adenocarcinoid types of tumor. The most common presentation was that of acute appendicitis. Interestingly, in no patients was the correct diagnosis made before surgery, and it was entertained intraoperatively in only 30 patients (32%). The cure 5-year survival rate was 55%, but it varied with stage (A, 100%; B, 67%; C, 50%; and D, 6%; p < 0.01) and with grade (I, 68%, and III, 7%; p < 0.01). Patients with the mucinous type had a better prognosis than those with the colonic type (p < 0.01). The survival rate was superior after right hemicolectomy versus appendectomy alone (68% vs. 20%, p < 0.001). Right hemicolectomy performed as a secondary procedure resulted in the upstaging of 38% of the patients' tumors. A second primary malignancy occurred in 33 patients (35%), of which 17 were located in the gastrointestinal tract. CONCLUSIONS: Primary adenocarcinoma of the appendix should be treated by right hemicolectomy, even if it is a secondary procedure. Surveillance for synchronous or metachronous tumors, especially in the gastrointestinal tract, is warranted.

Actuarial Analysis↗

Role of the duodenum in postprandial release of pancreatic and gastrointestinal hormones.

In previous studies we found that duodenectomy abolished the interdigestive cycles of plasma motilin and pancreatic polypeptide (PP). In the current studies, we tested the hypothesis that an intact duodenopancreatic axis is necessary for normal postprandial release of pancreatic (PP, insulin) and gut peptides (gastric inhibitory peptide, GIP; cholecystokinin octapeptides, CCK-8; neurotensin; and gastrin). Consequently, we measured plasma concentration of pancreatic and gut hormones in normal and duodenectomized dogs after gavage feeding of a 250-ml liquid formula diet in conscious animals. After completing the experiments, pancreatic tissue concentrations of PP and insulin were measured. Removal of the duodenum was associated with decreases in postprandial plasma concentrations of PP (p < 0.05) and insulin (p < 0.05) and in pancreatic tissue concentrations of insulin (p = 0.01). Duodenectomy, however, did not alter postprandial plasma concentrations of GIP, CCK-8, neurotensin, or gastrin nor pancreatic tissue concentrations of PP. These effects of duodenectomy may be due to disruption of duodenopancreatic neural connections or loss of vagus sensitive (non-GIP) humoral factors. Decreased postprandial insulin concentrations may be due to lack of a neural or humoral insulinotropic factor arising from the duodenum.

Animals↗

Pancreatic lymphoma: is it a surgical disease?

Primary pancreatic lymphoma is a rare neoplasm that reportedly regresses promptly with aggressive chemotherapy. Recently, the role of surgical management has been relegated to biopsy alone. The aim of this study was to review our experience with primary pancreatic lymphoma and to determine the outcome of patients managed by radiation therapy and/or chemotherapy. From 1952 to 1991, 107 patients with non-Hodgkin's lymphoma involving the pancreas were identified. Twelve patients (11%) had primary pancreatic lymphoma. The presenting symptoms and signs were nonspecific: abdominal pain (83%), weight loss (50%), and a palpable mass (58%). Six of the 12 patients (50%) undergoing celiotomy had a preoperative diagnosis of pancreatic carcinoma. These lymphomas were large (x = 8 +/- 2 cm) and deemed unresectable because of size, alleged mesenteric vessel encroachment, regional lymph node metastasis, or because of an intraoperative diagnosis of lymphoma. Biopsy alone was performed in 50% of patients and biliary bypass and/or gastroenterostomy was performed in 25% of patients. A single resection (pancreatoduodenectomy) was performed 1 year after a full course of chemotherapy had failed. Ten patients, all of whom died of progressive lymphoma, received primary postoperative radiation therapy and/or chemotherapy, and no patient was disease-free at follow-up. Mean survival was 13 months for patients who received chemotherapy alone (n = 2), 22 months for those treated with radiation therapy only (n = 5), and 26 months for those receiving combined radiation therapy and chemotherapy (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Jejunal responses to absorptive and secretory stimuli in the neurally isolated jejunum in vivo.

BACKGROUND: Our aim was to assess changes in transport of water and electrolytes under basal, proabsorptive, and prosecretory conditions after an in situ neural isolation of the jejunoileum. METHODS: Eight dogs underwent intraoperative perfusion of 50 cm of jejunum with a balanced electrolyte solution during sham operation and after neural isolation of the jejunoileum. Jejunal perfusion studies were later conducted in seven conscious dogs with a triple-lumen technique before and 2 and 8 weeks after neural isolation of the jejunoileum during intravenous infusion of 150 mmol/L sodium chloride (basal conditions), vasoactive intestinal polypeptide (VIP conditions), 500 pmol/kg per hour (prosecretory conditions), and the alpha 2-adrenergic agonist alpha-methylnorepinephrine (MNE), 900 nmol/kg per hour (proabsorptive conditions). RESULTS: Neural isolation decreased intraoperative net absorption of water (4.4 +/- 0.9 vs 2.2 +/- 0.5 microliters/cm/min; p < 0.05) and electrolytes (sodium, chloride, bicarbonate, potassium). In conscious dogs during basal conditions, net absorptive flux was decreased (p < 0.05) at 2 but not at 8 weeks. VIP produced similar absolute decreases in net absorptive flux at all three time points. MNE increased net absorption before and at 8 weeks, but not at 2 weeks after autotransplantation. CONCLUSIONS: In situ neural isolation of the jejunoileum decreased net basal jejunal absorption of water and electrolytes immediately and for at least 2 weeks. Proabsorptive responses to MNE but not prosecretory responses to VIP were altered at 2 weeks. Jejunal adaptation allowed absorptive function to return to near normal by 8 weeks.

Animals↗

Use of gastroduodenal manometry to differentiate mechanical and functional intestinal obstruction: an analysis of clinical outcome.

OBJECTIVES: Our aim was to assess the outcome of patients whose gastrointestinal motility recording suggested intestinal mechanical obstruction. METHODS: Medical records were reviewed for operative reports and alternative diagnoses during at least 1-yr follow-up. RESULTS: During 1988-1992, 27 of 890 consecutive manometric recordings suggested mechanical obstruction: 20 with non-propagated, prolonged contractions, seven with a pattern of non-propagated clustered contractions that lasted > 30 min. Obstruction was confirmed at laparotomy in 17 (including two with progressive systemic sclerosis) and by radiology in one. In confirmed obstruction, 12 of 18 contrast radiographs performed prior to manometry were either normal or nondiagnostic. One laparotomy was negative for obstruction; nine patients who did not undergo laparotomy were classified as unobstructed. Manometric recordings showed prolonged contractions in two, clustered contractions in three, and a mixed pattern in four. Positive predictive values of these patterns for obstruction were: prolonged contractions, 82%; clustered contractions, 57%; and mixed pattern, 56%. CONCLUSIONS: Thus, non-propagated, prolonged contractions in small bowel should prompt a search for obstruction, even when this is equivocal on barium small bowel radiography.

Adolescent↗

Diagnosis and management of gastric emptying disorders.

In summary, although gastric emptying disorders are relatively uncommon, they are potentially devastating conditions resulting from pathophysiologic motor disturbances. Rapid gastric emptying of liquids is the hallmark of the dumping syndrome and occurs after operations, including vagotomy. Vagal denervation abolishes receptive relaxation and accommodation in the proximal stomach (the storage site for ingested liquids) resulting in increased intragastric pressure which forces liquids through an ablated or bypassed pylorus. Dumping symptoms may occur in up to 50% of postgastrectomy patients, but most patients are treated satisfactorily by dietary manipulation or, in the rare incapacitated patient, by the long-acting somatostatin analogue octreotide. Reconstructive gastric surgery may rarely be indicated to slow gastric emptying and alleviate the dumping syndrome. Reoperative procedures include pyloric reconstruction after pyloroplasty, small intestinal pouches, interposed isoperistaltic and antiperistaltic jejunal segments, and a Roux-en-Y gastrojejunostomy. Interposed jejunal loops and the Roux-en-Y gastrojejunostomy provide the most satisfactory results. Delayed gastric emptying may occur in the acute postoperative period or be a late complication of gastric surgery. Loss of vagal input to the gastric antrum and resection of the antrum with vagotomy may produce an atonic stomach or atonic gastric remnant, respectively, which fails to grind and propel solids into the small intestine. Scintigraphic imaging of both the liquid and solid components of the meal is a valuable diagnostic adjunct. Gastric ileus occurring in the early postoperative period generally resolves within 6 weeks of operation, and the temptation to reoperate on a nonobstructed stomach should be avoided. Pharmacologic therapy of chronic gastric stasis with the benzamide prokinetic agents (metoclopramide, cisapride, renzapride), domperidone, and the motilin agonist erythromycin, may be effective initially, but long-term results are still undefined, and postvagotomy and postgastrectomy patients have not been studied adequately. Persistent postoperative gastric atony and the Roux stasis syndrome should be managed surgically by near-total gastrectomy which should result in symptomatic improvement in two thirds of patients.

Gastrectomy↗

Absorption of simple nutrients from the in vivo neurally isolated canine jejunum and ileum.

BACKGROUND: The effects of intestinal transplantation on enteric absorptive function are not well understood. Our aim was to determine the effects of in situ isolation of the jejunoileum, a large animal model of jejunoileal autotransplantation, on absorption of simple nutrients from the jejunum and ileum separately. METHODS: Four groups of dogs were prepared with modified Thiry-Vella loops: group 1, neurally intact jejunum; group 2, neurally isolated jejunum; group 3, neurally intact ileum; and group 4, neurally isolated ileum. Intestinal loops were perfused with five different isosmolar solutions of NaCl alone, 30 mmol/L glucose, 2.5 mmol/L glycine, 2.5 mmol/L phenylalanine, and 5 mmol/L oleic acid at 1 to 2 weeks and 8 to 9 weeks after operation. RESULTS: Net absorption of water and electrolytes, glucose, glycine, phenylalanine, and oleic acid were not different statistically between neurally intact and neurally isolated intestinal loops at either time point. Ileal loops absorbed more than jejunal loops. CONCLUSIONS: Absorption of simple nutrients from the canine jejunum and ileum is not altered by this model of intestinal autotransplantation. These observations suggest that the extrinsic denervation that accompanies intestinal transplantation does not affect the transport systems for glucose, glycine, phenylalanine, or oleic acid.

Amino Acids↗

Intraluminal measurement of enteric mucosal perfusion: relationship to superior mesenteric artery flow during basal and postprandial states in the dog.

BACKGROUND: Several in vivo techniques that assess mucosal perfusion by intraluminal probes have recently been developed and validated, including laser Doppler flowmetry, reflectance spectrophotometry, and tonometry. METHODS: With these techniques, a canine model where the entire vascular supply to the jejunoileum was isolated as the superior mesenteric artery and vein was used to examine the relationship between enteric mucosal blood perfusion and adjusted decrements in arterial flow under fasting and postprandial conditions. RESULTS: Mucosal perfusion measured by laser Doppler flowmetry and reflectance spectrophotometry correlated linearly with decrements in superior mesenteric artery flow (r2 = 0.96 and 0.98, respectively); estimation of mucosal pH by tonometry decreased only after a critical level of arterial inflow was reached (less than 50% of baseline flow). Mucosal perfusion increased after the meal throughout the jejunoileum with unrestricted superior mesenteric artery flow. However, with restricted superior mesenteric artery flow, nutrient delivery to the jejunum was accompanied by increased mucosal perfusion at that level but by decreased perfusion in the distal ileum not exposed to nutrients. This latter response represents a distal to proximal redistribution of blood, i.e., an intramesenteric steal phenomenon. CONCLUSIONS: In vivo measurements of mucosal perfusion reflected changes in large mesenteric vessel blood flow. These intraluminal techniques discriminated between a normal and an impaired mesenteric circulation in an acute model and may have clinical application.

Animals↗

Enteroendocrine peptides in a canine model of orthotopic jejunoileal autotransplantation.

The enteroendocrine cells of the small bowel provide a rich source of regulatory peptides involved in the modulation of gastrointestinal function. Recent work from our laboratory showed that in situ neural isolation (autotransplantation) of the jejunoileum produced marked changes in tissue expression of several neuropeptides. In the present study, we examined the influence of extrinsic innervation on the tissue expression of endocrine peptides localized to various regions of the gastrointestinal tract. Concentrations of immunoreactive gastric inhibitory polypeptide (GIP), neurotensin (NT) and peptide tyrosine tyrosine (PYY) in fasting plasma and regional tissue biopsies were determined before and at varying time points (2, 6, 12 weeks) after a model of canine orthotopic jejunoileal autotransplantation. GIP was not altered in plasma or tissue at any time point. Plasma concentrations of NT and PYY increased after autotransplantation. Following a decrease in tissue concentrations two weeks after autotransplantation, NT increased progressively from 2 to 6 to 12 weeks, reaching a maximal increase of 895% over baseline in proximal ileum. Tissue concentrations of PYY followed much the same pattern as NT, but these trends never achieved statistical significance. Chromatographic characterization of tissue biopsy extracts revealed molecular heterogeneity of NT-like immunoreactivity, while GIP and PYY immunoreactivity coeluted as single species with authentic standards. Taken together with our earlier observations, it appears that disruption of extrinsic and intrinsic neural continuity to the jejunoileum (autotransplantation) does not affect gut endocrine peptides such as GIP and PYY to the same extent as enteric neuropeptides. NT has been localized to neural as well as endocrine cells and is involved in the temporal adaptive response to autotransplantation.

Animals↗