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Biomedical subjects

M G Sarr

Publications and source records attributed to M G Sarr.

At least 91 records · Page 5Linked to original sources
PubMed1998

Eosinophil infiltration and degranulation in normal human tissue.

Localization of eosinophil granule major basic protein by immunofluorescence permits recognition of both eosinophil infiltration and degranulation. Over the past decade and a half, our laboratory has shown that eosinophil infiltration and degranulation occur in many diseased tissues in humans; among normal tissues studied as controls, only the gut showed striking eosinophil infiltration and degranulation. Using an indirect immunofluorescence procedure for the detection of major basic protein, we extended our analyses of normal human tissues to include tissues from essentially all body organs; a total of 117 biopsy/autopsy specimens were analyzed. To determine whether the method of tissue procurement affected the level of eosinophil degranulation in the normal gastrointestinal tract, normal proximal jejunum from six patients was biopsied using either an endoscopic forceps or a scalpel at the time of elective surgery and examined by immunofluorescence. Spleen, lymph node, and thymus tissues showed eosinophil infiltration with scant evidence of degranulation, but the only organ showing both eosinophil infiltration and remarkable degranulation was the gastrointestinal tract. Eosinophil degranulation was significantly increased in specimens obtained by endoscopic forceps compared to those obtained by scalpel (P = 0.021). These results indicate that tissue procurement methods affect the degree of eosinophil degranulation in the gut. Thus, among normal human body organs, both eosinophil infiltration and appreciable degranulation consistently occur only in the gut.

Adult↗
PubMed1998

Ischemic necrotizing pancreatitis. Two case reports and review of the literature.

Pancreatic ischemia is a very rare etiology of clinical acute pancreatitis, complicating cardiac surgery, hemorrhagic shock, and transplantation of the pancreas. In this article, we present two patients with acute ischemic necrotizing pancreatitis, complicating a generalized atheromatous disease with extensive lesions in the splanchnic circulation (patient 1) and repair of a descending thoracic aortic aneurysm (patient 2). Diagnostic approach and management of ischemic necrotizing pancreatitis are discussed.

Aged↗
PubMed1998

Management of necrotizing pancreatitis by repeated operative necrosectomy using a zipper technique.

METHODS: From 1983 to 1995, 72 patients with necrotizing pancreatitis were treated with a general approach involving planned reoperative necrosectomies and interval abdominal wound closure using a zipper. RESULTS: Hospital mortality was 25%. Multiple organ failure without sepsis caused early mortality in 3 of 4 patients and sepsis caused late mortality in 11 of the remaining 14. The mean number of reoperative necrosectomies/debridements was 2 (0 to 7). Fistulae developed in 25 patients (35%); 64% were treated conservatively. Recurrent intraabdominal abscesses developed in 9 patients (13%) but were drained percutaneously in 5. Hemorrhage required intervention in 13 patients (18%). Prognostic factors included APACHE-II score on admission < 13 (P = 0.005), absence of postoperative hemorrhage (P = 0.01), and peripancreatic tissue necrosis alone (P < 0.05). CONCLUSIONS: The zipper approach effectively maximizes the necrosectomy and decreases the incidence of recurrent intraabdominal infection requiring reoperation. APACHE-II score > or = 13, extensive parenchymal necrosis, and postoperative hemorrhage signify worse outcome.

APACHE↗
PubMed1998

Effect of motilin and erythromycin on calcium-activated potassium channels in rabbit colonic myocytes.

BACKGROUND & AIMS: Motilin and erythromycin are prokinetic agents that act on the same receptor in gastrointestinal smooth muscle to cause contraction. Both agonists may also cause an increase in outward current. The aim of this study was to determine whether motilin and erythromycin activate calcium-activated potassium (KCa) channels. METHODS: Freshly dispersed longitudinal smooth muscle cells of the rabbit colon were used to measure whole-cell outward current and single-channel activity using patch clamp recording methods. RESULTS: Erythromycin and motilin increased a calcium-dependent outward potassium current and increased the open probability of KCa channels of cell- attached patches. CONCLUSIONS: Erythromycin and motilin activate KCa channels via an intracellular second messenger system. This effect may modulate the increase in contractility caused by these agonists.

Animals↗
PubMed1998

Functional changes in nonadrenergic, noncholinergic inhibitory neurons in ileal circular smooth muscle after small bowel transplantation in rats.

This experiment was designed to determine mechanisms of change in nonadrenergic, noncholinergic (NANC) inhibitory neurons in the ileum after small bowel transplantation (SBT) in the rat and whether nitric oxide (NO) serves as an important NANC inhibitory neurotransmitter in the rat ileum. Eight groups of rats (N > or =8 rats/group) were studied: neurally intact unoperated controls; rats one week after anesthesia and sham celiotomy; and separate groups one and eight weeks after either 40 min of cold ischemia of the jejunoileum, combined jejunal and ileal intestinal transection/reanastomosis, or orthotopic SBT of the entire jejunoileum. Contractile activity was evaluated in full-thickness ileal circular muscle strips under isometric conditions. Spontaneous activity did not differ among groups. In all groups, exogenous NO, NG-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor), and methylene blue (soluble guanylate cyclase inhibitor) had no effect on spontaneous activity, while 8-bromocyclic guanosine monophosphate (8Br-cGMP) inhibited contractile activity in all groups. Low frequency (2-10 Hz) electrical field stimulation (EFS) inhibited contractile activity only in control and SBT groups; L-NMMA and methylene blue did not alter the response to EFS in any group. These results suggest that each aspect of the SBT procedure, ischemia/reperfusion injury, disruption of enteric neural continuity by intestinal transection, and extrinsic denervation, alter function of enteric ileal inhibitory neurons separately early (one week) after operation. NO, a known inhibitory neurotransmitter in other gut regions, does not affect ileal circular muscle in neurally intact tissue nor mediate functional changes in inhibitory nerve function nor smooth muscle contractility after SBT.

Animals↗
PubMed1998

Long-term outcome of necrotizing pancreatitis treated by necrosectomy.

BACKGROUND: Long-term functional outcome after operative treatment of necrotizing pancreatitis (NP) has not been studied extensively. METHODS: Pancreatic function, performance status, recurrence of symptoms and other related problems were analysed in 44 consecutive patients successfully discharged from hospital after operative necrosectomy (1983-1995) and followed up completely for a mean of 5 years. RESULTS: Clinical pancreatic insufficiency developed in half the patients. Diabetes mellitus (11 patients), steatorrhoea (six) or both (five) were associated with a mean estimate of 52, 66 and 67 per cent parenchymal necrosis respectively. Normal pancreatic function was associated with 27 per cent parenchymal necrosis (P < 0.05). Diabetes worsened while steatorrhoea tended to improve over time. Abdominal pain and pancreatitis recurred in six and two patients respectively. Performance status worsened in four patients because of recurrent pancreatitis and severe steatorrhoea. Poor long-term performance was associated with a higher Acute Physiology And Chronic Health Evaluation II score on admission (mean 14 versus 9). CONCLUSION: NP has prominent effects on long-term pancreatic exocrine and endocrine function in half the patients, but most preserve a good overall functional status. The development of pancreatic insufficiency varies with the extent of pancreatic parenchymal necrosis.

APACHE↗
PubMed1998

Duodenal motility in fasting dogs: humoral and neural pathways mediating the colonic brake.

We have previously described a negative feedback loop that inhibits duodenal motility when nutrients are infused into the ileum and colon. In the present study, we examined the role of extrinsic innervation and plasma levels of peptide YY (PYY) in mediating this phenomenon. We perfused neurally intact (n = 5 dogs) or extrinsically denervated (n = 6 dogs) isolated loops of proximal colon with isomolar NaCl or a mixed-nutrient solution at 2 and 6 ml/min for 4 h during fasting or for 2 h beginning 15 min after a meal. Both rates of infusion with NaCl prolonged the cycle length of the duodenal migrating motor complex (MMC) in the group with neurally intact loops but not in the group with extrinsically denervated loops. Nutrient infusions increased the MMC cycle length in both groups. Integrated plasma concentrations of PYY were increased by nutrients but not by NaCl in both groups. These data suggest that increased volumes and unabsorbed nutrients in the proximal colon alter proximal small bowel motility. Volume-induced effects are mediated via extrinsic nerves, whereas nutrient-induced effects may be mediated by humoral factors, such as plasma PYY.

Animals↗
PubMed1998

Effect of nitric oxide on calcium-activated potassium channels in colonic smooth muscle of rabbits.

Nitric oxide (NO) hyperpolarizes intestinal smooth muscle cells. This study was designed to determine the mechanism whereby NO activates KCa channels of circular smooth muscle of the rabbit colon. Transmural biopsies of the rabbit colon were stained for NADPH-diaphorase. Freshly dispersed circular smooth muscle cells were studied in the whole cell configuration, as well as in on-cell and excised inside-out patch recording configurations, while KCa current and the activity of KCa channels, respectively, were monitored. NADPH-diaphorase-positive nerve fibers were found in both muscle layers. NO (1%) increased whole cell net outward current by 79% and hyperpolarized resting membrane voltage from -59 to -73 mV (n = 8 cells, P < 0.01). In the on-cell patch recording configuration. NO (0.5% or 1%) in the bath increased NPo of KCa channels; charybdotoxin (125 nM) in the pipette solution blocked this effect. In the excised inside-out patch recording configuration, NO (1%) had no effect on NPo of KCa channels. In the on-cell patch recording configuration, methylene blue (1 microM) or cystamine (5 mM) in the bath solution decreased the effect of NO (1%) on NPo of KCa channels. NPo was increased by 8-bromo-cGMP (8-BrcGMP; 1 mM), a cGMP analog, and zaprinast (100 microM), an inhibitor of cGMP phosphodiesterase. These data suggest that NO increased whole cell outward K+ current by activating KCa channels through a cGMP pathway.

Animals↗
PubMed1998

Canine small bowel motor patterns and contractions are not neurally regulated during enteric nutrient infusion.

The aims of this study were to determine the effects of duodenal and jejunoileal nutrient infusions on small intestinal motor patterns and intestinal contractions in neurally intact and neurally isolated small bowel. Fifteen dogs were prepared with duodenal and jejunal infusion and manometry catheters and a diverting jejunal cannula. Ten of the dogs underwent in situ neural isolation of the jejunoileum. A mixed nutrient meal (0.5 kcal/ml) was infused into the duodenum or jejunum at 3 ml/min for 5 h. Control experiments involved infusion of a balanced salt solution. Manometric data collected on-line to a microcomputer were analyzed for direction, distance, and velocity of spread of single pressure waves (SPW) and clustered contractions. Isolated duodenal and jejunoileal nutrient infusions inhibited the fasting motor pattern in neurally intact and neurally isolated small bowel. Motor activity (motility index) increased slightly during nutrient infusion within groups, but there were few differences between groups. Neither neural isolation nor nutrient infusion had a consistent effect on spread of SPW or migration of clustered contractions. Isolated duodenal and jejunoileal nutrient infusions in the dog inhibit fasting motor patterns and increase motor activity slightly but have little effect on characteristics of individual and clustered contractions. Extrinsic innervation to the jejunoileum or intrinsic neural continuity of the jejunum with the duodenum had little effect on single or grouped contractions. Although the changes in motor activity demonstrated in this study appear small, alterations in intestinal transit and absorption may still occur and may be of importance physiologically.

Animals↗
PubMed1998

Pancreas-preserving total duodenectomy.

The concept of operations to be 'as resective as necessary and as organ-preserving as possible' has led to the novel technique of resection of the entire duodenum, with complete preservation of the head of the pancreas, as a better alternative to the classic pancreaticoduodenectomy. This operation requires meticulous technique and precise knowledge of pancreatic and peripancreatic anatomy. Indications include benign or premalignant conditions confined to the duodenal mucosa, usually familial adenomatous polyposis. When appropriately performed, pancreas-preserving total duodenectomy leads to shorter operative time, requires less and safer anastomoses, and optimizes postoperative endoscopic surveillance. The available long-term results are encouraging.

Adult↗
PubMed1998

Extrinsic innervation modulates canine jejunal transport of glutamine, alanine, leucine, and glucose.

BACKGROUND: We previously showed a decrease in ileal glutamine transport in vitro and net absorption in vivo after extrinsic denervation of the canine jejunoileum. The aim was to determine whether extrinsic innervation modulates in vivo net absorption and in vitro transport of glutamine and other nutrients in canine jejunum. METHODS: In vivo net jejunal uptakes of glutamine, alanine, leucine, and glucose were measured in five dogs before and 2 and 8 weeks after a model neurally isolating in situ the jejunoileum (extrinsic denervation, intestinal transection). To assess mechanisms, carrier-mediated uptakes were quantitated in jejunal brush border membrane vesicles from six dogs before and at 2 and 8 weeks after neural isolation of the jejunoileum and compared with six control dogs with fully intact extrinsic innervation. RESULTS: In vivo net absorption of glutamine decreased at 2 weeks (p < 0.05) and returned to normal values at 8 weeks; net absorptions of leucine, alanine, and glucose were decreased at both 2 and 8 weeks. In vitro brush border membrane vesicles transport of glutamine, leucine, and alanine followed the patterns of in vivo absorption, but glucose transport did not differ at any time point. Decreased glutamine uptake at 2 weeks resulted from a decrease in Vmax rather than a change in K(m) in sodium-dependent carrier-mediated transport. CONCLUSIONS: Extrinsic denervation down-regulated carrier-mediated transport of amino acids but not glucose. Decreased in vitro glutamine transport was mediated in part by a decrease in number rather than affinity of sodium-dependent transporters.

Alanine↗
PubMed1997

Pancreatic ascites: a rare complication of necrotizing pancreatitis. A case report and review of the literature.

We describe a young patient with a family history of hereditary pancreatitis who developed extensive pancreatic necrosis complicated by pancreatic ascites. Because of failure of medical management, he was successfully treated with operative necrosectomy and primary wound closure over peripancreatic drains. A postoperative low-output pancreaticocutaneous fistula resolved with time. Pancreatic ascites, as a result of pancreatic duct disruption, is more common in chronic rather than acute pancreatitis and is exceedingly uncommon in the context of necrotizing pancreatitis. When it complicates the latter, treatment should be guided by the principles of management of necrotizing pancreatitis. However, when true pancreatic ascites persists, the pancreatic duct anatomy and site of leak should be defined with endoscopic retrograde pancreatography (ERP). Treatment options include endoscopic duct dilatation and stent placement (if a stricture exists proximal to the leak), onlay pancreaticojejunostomy, or distal pancreatectomy (especially if the leak is located in the distal pancreas or in an enterically isolated distal pancreas).

Adult↗
PubMed1997

Laparoscopic colectomy shortens postoperative ileus in a canine model.

BACKGROUND: Proponents of laparoscopic colectomy claim a more rapid return of gastrointestinal function, but objective data supporting this contention are lacking. Our aim was to compare the duration of delay in gastrointestinal transit after total laparoscopic, laparoscopic-assisted, and open colonic resection. METHODS: Thirty-nine female dogs were assigned to three groups: group 1, laparoscopic colectomy; group 2, laparoscopic-assisted colectomy; and group 3, open colectomy. Transit studies were performed before operation and on days 1, 2, 3, and 5 after a mid-descending colectomy with end-to-end anastomosis. Gastric emptying of liquids and small bowel transit of liquids were determined by means of radionuclide techniques. Gastric emptying of solids and colonic transit were measured by following transit of radiopaque spheres instilled into the stomach and proximal colon, respectively. RESULTS: With each dog as its own control, gastric emptying returned to preoperative values by 2 days in group 1, 3 days in group 2, and 5 days in group 3. Small bowel transit returned to preoperative values on day 3 for groups 1 and 2 and on day 5 for group 3. Gastric emptying of solids and colonic transit returned to preoperative values on day 3 for group 1 and on day 5 for groups 2 and 3. CONCLUSIONS: These observations show that laparoscopic resection techniques in this canine model resulted in a more rapid return to normal gastrointestinal transit compared with open colectomy.

Animals↗
PubMed1997

In situ neural isolation of the entire canine upper gut: effects on fasting and fed motility patterns.

BACKGROUND: Multiorgan upper gut transplantation is becoming clinically feasible; however, the effects of multivisceral transplantations on gastrointestinal motility are unknown. Our aim was to determine the neural and hormonal mechanisms controlling motility patterns after complete extrinsic denervation of the upper gut as a model of multivisceral upper gut autotransplantation. METHODS: Seven dogs successfully underwent in situ neural isolation of the stomach, entire small intestine, proximal colon, liver, and pancreas by transecting all connections (distal esophagus, midcolon, all nerves, lymphatics) to this multivisceral complex except the celiac artery, superior mesenteric artery, and the suprahepatic and infrahepatic vena cava; these vessels were meticulously stripped of adventitia under optical magnification. Blood flow was not disrupted to prevent confounding effects of ischemia-reperfusion injury. After 1- to 2-week recovery, myoelectric and manometric recordings of stomach and myoelectric recordings of small bowel were obtained from conscious animals. RESULTS: During fasting the characteristic cycling migrating motor complex (MMC) was observed in the stomach and small intestine. The gastric component of the MMC was absent in one of the seven dogs. Regular cycling of the MMC during fasting, however, was intermittently disrupted and replaced by a noncyclic pattern of intermittent contractions in two of seven dogs 43% of the recording time. A small meal (50 gm liver) did not abolish the MMC as occurs in normal dogs; in contrast, a large meal (500 gm liver) did abolish the MMC. CONCLUSIONS: Extrinsic innervation to the upper gut modulates but is not requisite for interdigestive and postprandial motility of the stomach. Because relatively normal global motility patterns are preserved, multivisceral upper gut transplantation should be a viable option in selected patients.

Animals↗
PubMed1997

Effects of ethyl alcohol on canine jejunal circular smooth muscle.

Ethyl alcohol has many symptomatic effects on the gastrointestinal tract. Our aim was to determine the effects of ethyl alcohol on circular smooth muscle contractility of the canine small bowel. Mechanical and intracellular electrical recordings were made in vitro from the circular muscle of full-thickness strips of muscularis externa from canine jejunum. Ethyl alcohol (20-120 mM) dose-dependently decreased spontaneous contractile amplitude, hyperpolarized the resting membrane potential, and decreased the amplitude of the slow wave. Ethyl alcohol also decreased the amplitude of the inhibitory junction potential (during electrical field stimulation-EFS) but did not alter the maximum absolute cell-polarized potential reached during EFS. An increase in extracellular calcium (15 mM) partially restored spontaneous contractile amplitude, resting membrane potential, and slow-wave amplitude. Ethyl alcohol decreased the amplitude of contractions evoked by acetylcholine, CCK, and substance P. These data suggest that ethyl alcohol has direct effects on jejunal smooth muscle contractility. These effects can be partially reversed by increasing the availability of extracellular calcium.

Animals↗
PubMed1997

Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.

Effects of small bowel transplantation (SBT) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SBT in rats. Orthotopic SBT was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/ reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.

Adrenergic Agonists↗