Raphael Udassin

Age-related changes in the morphology of the myenteric plexus of the human colon

Aging is believed to affect the structure and function of the enteric nervous system, but little specific information on this topic is available, particularly in humans. The aim of this study was to investigate the effect of age on the structure of myenteric ganglia in the human colon. We examined myenteric ganglia in colonic specimens obtained from 168 patients aged 10 days to 91 years. Nerves were stained in whole mount preparations using the vital fluorescent dye 4-(4-dimethylaminostyryl)-methylpyridinium iodide (4-Di-2-ASP) and other staining methods. Human myenteric ganglia were classified into three types: normal, those containing empty spaces (cavities) and those containing large nerve fiber bundles. We found a statistically significant increase with age in the proportion of ganglia with cavities. Conversely, there was a decrease with age in the proportion of normal ganglia. The proportion of fiber-containing ganglia did not change with age. These findings indicate that there is an increase with age in the number of abnormally appearing myenteric ganglia in the human colon, which may contribute to the disturbed colonic motility in the aging population.

Postischemic intestinal motility in rat is inversely correlated to length of ischemia

An inverse correlation between postischemic gastrointestinal motility and the length of intestinal ischemia was found in an animal model. Intestinal ischemia was caused without concurrent laparotomy and for a predetermined time period (ischemia time) by pulling on an external nylon thread that was threaded through a double-lumen catheter. This catheter was passed into the abdominal cavity to encircle the superior mesenteric artery. Gastrointestinal motility was determined by the introduction of a color-marked meal into the animals stomach and the measurement of the proportionate length of the small bowel filled with it (transit index). This simple and reliable animal model can also be used for the evaluation of techniques and pharmacological manipulations aimed at modulation of the effects of intestinal ischemia on intestinal motility and its consequences.

Nitric oxide-containing nerves in bowel segments of patients with Hirschsprung's disease.

To assess the role of nerves that synthesize nitric oxide (NO) in Hirschsprungs Disease (HD), the authors studied the distribution of the enzyme NADPH diaphorase (NADPHd) in normal and diseased bowel segments. In the proximal (ganglionic) segment of the colon, NADPHd-positive neurons were present in both myenteric and submucosal plexuses. In the distal involved colonic segments from HD patients, the typical pattern of the neuronal network was completely missing in the regions of the two plexuses; instead, only disorganized NADPHd-positive nerve fibers were present and NADPHd-reactive neurons were absent. Mucosal NO synthase activity was 2.76 +/- 0.38 nmol/g/min in the proximal segment and only 0.83 +/- 0.49 nmol/g/min in the distal segment (P < .05, N = 3).

Comparison of Pediatric Appendectomy Outcomes Between Pediatric Surgeons and General Surgery Residents

BACKGROUNDnAppendectomy is the most common urgent procedure in children, and surgical outcomes may be affected by the surgeons experience. This studys aim is to compare appendectomy outcomes performed by pediatric surgeons (PSs) and general surgery residents (GSRs).nnnMATERIALS AND METHODSnA retrospective review of all patients younger than 16y treated for appendicitis at two different campuses of the same institution during the years 2008-2009 was performed. Appendectomies were performed by PS in one campus and GSR in the other. Primary end points included postoperative morbidity and hospital length of stay.nnnRESULTSnDuring the study period, 246 (61%) patients were operated by senior GSR (postgraduate year 5-7) versus 157 (39%) patients by PS. There was no significant difference in patients characteristics at presentation to the emergency room and the rate of appendeceal perforation (11% versus 15%, P=0.32), and noninfectious appendicitis (5% versus 5% P=0.78) also was similar. Laparoscopic surgery was performed more commonly by GSR (16% versus 9%, P=0.02) with shorter operating time (54±1.5 versus 60±2.1, P=0.01). Interestingly, the emergency room to operating room time was shorter for GSR group (419±14 versus 529±24min, P<0.001). The hospital length of stay was shorter for the GSR group (4.0±0.2 versus 4.5±0.2, P=0.03), and broad-spectrum antibiotics were used less commonly (20% versus 53%, P<0.0001) and so was home antibiotics continuation (13% versus 30%, P<0.0001). Nevertheless, postoperative complication rate was similar (5% versus 7%, P=0.29) and so was the rate of readmissions (2% versus 5%, P=0.52).nnnCONCLUSIONSnThe results of this study suggest that the presence of a PS does not affect the outcomes of appendectomies.

Laparoscopic Nissen fundoplication in children under 2 years of age

AbstractBackground: Antireflux operations have been recommended for infants and children suffering from complications related to gastroesophageal reflux (GER). In recent years, the laparoscopic approach has been used increasingly for antireflux surgery in adult patients. This is our initial experience with Nissen fundoplication in infants and children under 2 years of age.n Patients: We operated on 11 patients weighing between 3.0 and 10.0 kg. The main indications for surgery were GER-induced aspiration pneumonia and failure to thrive, in spite of intensive conservative treatment. All patients except one had an associated neurological abnormality, including six patients with familial dysautonomia.n Results: All attempted operations were completed successfully laparoscopically, with only a few postoperative complications and acceptable short-term results. The clinical considerations and technical aspects unique to this specific group of patients are discussed.n Conclusion: Laparoscopic Nissen fundoplication is feasible, safe, and effective, even in very small babies.

Decreased density of ganglia and neurons in the myenteric plexus of familial dysautonomia patients

BACKGROUNDnFamilial dysautonomia (FD) is a hereditary disease of the autonomic and sensory nervous system. A prominent manifestation of FD is gastrointestinal dyscoordination, which contributes to the morbidity and mortality in FD.nnnAIMnAs the myenteric plexus is an essential factor in gastrointestinal motility control, we compared its morphology in appendices of FD patients and controls.nnnMETHODSnAppendices from FD patients (N=19) were obtained during surgery of fundoplication and gastrostomy; normal appendices (N=17) were obtained from patients suspected to suffer from acute appendicitis, in whom, however, the appendix was found to be normal. Specimens were stained histochemically for NADPH diaphorase (NADPH-d) and in a blinded manner examined under a light microscope for seven morphologic parameters: ganglionic density, neuronal density, ganglionic area, number of stained neurons per ganglion, nerve bundle width, ratio between nervous tissue area and total area, and neuronal area.nnnRESULTSnGanglionic density was 10.13 per mm(2) in controls versus 5.01 per mm(2) in FD (p<0.05). Neuronal density was 70.12 per mm(2) in controls, compared with 22.09 per mm(2) in FD (p<0.01). The other parameters were not different between the two groups.nnnCONCLUSIONnDensities of myenteric ganglia and neurons of FD patients were significantly lower than in controls. This deficiency may contribute to the pathogenesis of FD gastroenteropathy.

Is non-operative intussusception reduction effective in older children? Ten-year experience in a university affiliated medical center

Ileo-colic intussusception in older children is frequently caused by a pathological lead point. Therefore, in many cases, no attempts at hydrostatic or air reduction are performed in non-pediatric hospitals. This study summarizes our experience in management of intussusception in children aged 3xa0years or older, in order to determine its efficacy and safety in this age group. We retrospectively reviewed medical records and radiological images of 26 cases of intussusception in 24 children older than 3xa0years admitted to our hospital over a 10-year period. In one child no attempt of reduction was made. Three children underwent unsuccessful imaging-guided reduction and an underlying tumor was identified at surgery and resected. In 18 cases air reduction was successful and no pathological lead point was discovered. In four children hydrostatic or air reductions failed. Manual reduction was performed, with no predisposing cause found. No complications were observed in any of our patients. Older age is not a contraindication for imaging-guided intussusception reduction attempt. Most of these patients can benefit from such an attempt, thereby avoiding surgery.

Pentoxifylline attenuates ischemia/reperfusion injury to the small intestine in the rat

There is a large body of evidence that neutrophils may play an important role in the mucosal injury that follows ischemia of the intestine. Pentoxifylline (PTF), a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and restores intestinal blood flow following hemorrhagic shock and sepsis. The purpose of this study was to evaluate the protective properties of PTF in an ischemia-reperfusion model of the intestine and whether its action is mediated through tissue neutrophils as assessed by myeloperoxidase (MPO) determination. Intestinal ischemia of either 1 or 2 h was induced in rats by clamping the superior mesenteric artery, followed by a 17-min reperfusion period. PTF (25 mg/kg) or saline solution was injected IP 10 min prior to ischemia. Multiple bowel samples were harvested at the end of the reperfusion period and evaluated for histology and tissue MPO. PTF significantly changed the resultant histologic damage to the intestinal mucosa exerted by prolonged ischemia of 1 and 2 h duration, although the beneficial effect of PTF in this animal model was independent of the number of tissue neutrophils as assessed by tissue MPO levels. Pretreatment with PTF can thus reduce the histologic damage caused by prolonged ischemia to the intestine.

Effect of Morphine on Small Bowel Propulsion after Intestinal Ischemia

OPIOIDS are known to reduce the motility of both the colon and the small intestine. However, some investigators have reported, both in animal models and in humans, that morphine increases duodenal motility. In vivo studies of the effect of morphine on small bowel motility are complicated because most have been performed in the postoperative period, where the additional trauma of laparotomy and bowel manipulation had already affected bowel motility. Previous studies have reported that intestinal ischemia also causes prolonged inhibition of bowel motility. The effect of morphine on intestinal motility has not been well assessed in situations in which ischemic injury to the bowel occurs without concurrent surgical injury. Recently, Zhang et al. reported that in a rat model of intestinal ischemia and reperfusion, pretreatment with morphine before ischemia and reperfusion markedly attenuated intestinal injury. The aim of the current study was to evaluate the effect of morphine on small bowel propulsion activity in a rat model in which controlled bowel ischemia was caused without concurrent abdominal surgery.

Plasma-to-lumen clearance of para-aminohippurate can replace 51Cr EDTA clearance in the evaluation of intestinal mucosal injury

Abstract Intestinal mucosal injury of various degrees occurs in many clinical situations and is initially evidenced by altered mucosal permeability. The latter may be assessed in animal models by determination of plasma-to-intestinal lumen clearance of specific molecules, usually chromated 51Cr EDTA. The purpose of this study was to evaluate the usage of para-aminohippurate (PAH) as a substitute for the commonly used radioactive material, i.e., 51Cr-EDTA, in the evaluation of intestinal mucosal injury. An isolated loop of ileum was created in rats and constantly perfused with warmed normal saline. Both renal pedicles were ligated. Either 51Cr-EDTA (18.5u2009Bq/kg) or PAH (58u2009mg/kg) was injected IV. Fifteen-minute intestinal ischemia was produced by clamping the superior mesenteric artery immediately after the end of an equilibration period. The perfusate was collected for 10u2009min prior to the initiation of intestinal ischemia, during the last 10u2009min of ischemia, and during the following three 10-min periods of reperfusion. Blood samples were collected at the end of each collection period for the determination of either PAH or 51Cr-EDTA concentrations and the calculation of either PAH or 51Cr-EDTA plasma-to-lumen clearances. PAH and 51Cr-EDTA plasma-to-lumen clearances followed the same pattern in all five assessed periods with no statistical difference between the two. PAH plasma-to-lumen clearance is a feasible, reliable, and inexpensive method for the evaluation of ischemia/reperfusion injury to the intestinal mucosa. It can safely replace the commonly used method in animal models that utilizes radioactive materials such as 51Cr-EDTA.