Jorge G. Mogilner

Delay of surgery in acute appendicitis

BACKGROUND AND OBJECTIVES It is generally assumed that delayed diagnosis of acute appendicitis results in higher morbidity but this assumption is not strongly supported in the literature. We attempt to define the effect of patient and physician delay on the outcome of patients with acute appendicitis. PATIENTS AND METHODS We studied 486 patients admitted between 1980 and 1992. Patient delay in presenting to a physician and surgeon delay from hospital admission to operation were studied in relation to stage of disease at operation as well as to postoperative complications. RESULTS Postoperative complications occurred in 10% of cases with simple acute appendicitis versus about 20% of cases with gangrenous or perforated appendicitis (P <0.001). The mean patient delay from onset of symptoms to presentation to a physician was 1.7 days in simple acute appendicitis versus 2.3 days in gangrenous or perforated appendicitis (P <0.001). Mean surgeon delay was 13.6 hours in simple acute appendicitis versus 14.5 hours in advanced appendicitis (P = NS). CONCLUSION Delay in patient presentation adversely affects the stage of disease in acute appendicitis and leads to increased incidence of infectious complications and to prolonged hospital stay. Conversely, physician delay does not affect the stage of disease. A surgeons decision to observe patients in hospital in order to clarify the diagnosis is justified, as it does not adversely affect outcome.

Treatment with glutamine is associated with down-regulation of Toll-like receptor-4 and myeloid differentiation factor 88 expression and decrease in intestinal mucosal injury caused by lipopolysaccharide endotoxaemia in a rat

Recent evidence suggests that lipopolysaccharide (LPS) endotoxaemia in a rat causes significant mucosal injury. Our objective was to determine the effects of glutamine (Gln) on Toll‐like receptor 4 (TLR‐4), myeloid differentiation factor 88 (Myd88) and tumour necrosis factor (TNF)‐α receptor‐associated factor 6 (TRAF6) expression in intestinal mucosa following LPS endotoxaemia in a rat. For this purpose, male Sprague–Dawley rats were assigned randomly to one of three experimental groups of 10 rats each: (i) control rats underwent intraperitoneal (i.p.) injection of sterile saline once a day; (ii) rats were treated with LPS given i.p. once a day at a dose of 10 mg/kg for 48 h (two doses); and (iii) rats were pretreated with oral Gln given in drinking water (2%) 48 h before and following injection of LPS. Intestinal mucosal parameters, enterocyte proliferation and apoptosis were determined at death. TLR‐4 and MyD88 mRNA expression was measured with reverse transcription–polymerase chain reaction (RT–PCR). TLR‐4 and MyD88 protein expression were analysed by Western immunoblotting. We observed a statistically significant (P < 0·05) decrease in mucosal weight, mucosal DNA and enterocyte proliferation and a significant increase in enterocyte apoptosis in rat intestine, following LPS administration. These changes were attenuated significantly by dietary Gln. Expression of TLR‐4, MyD88 and TRAF6 mRNA in the mucosal ileum was significantly higher in LPS rats versus control rats (P = 0·0006, P = 0·0015, P = 0·03, respectively) as well as TLR‐4 and MyD88 protein expression. The administration of Gln reduced significantly the expression of TLR‐4, MyD88 and TRAF6 (P = 0·023, P = 0·014, P = 0·035, respectively) mRNA as well as TLR‐4 and MyD88 protein expression in ileum compared to LPS animals. We did not find a significant change in the expression of TLR‐4, MyD88 or TRAF6 in the jejunum of different groups. We conclude that treatment with Gln was associated with down‐regulation of TLR‐4, MyD88 and TRAF6 expression and concomitant decrease in intestinal mucosal injury caused by LPS endotoxaemia in a rat.

The effect of 100% oxygen on intestinal preservation and recovery following ischemia-reperfusion injury in rats.

Objective:Inhalation of oxygen improves the hemodynamic status and attenuates the inflammatory response after intestinal ischemia-reperfusion (IR). Yet, the use of hyperoxia is hindered by concerns that it could exacerbate reperfusion injury by increasing free radical formation. We examined the effect of hyperoxia on enterocyte turnover and intestinal preservation and rehabilitation following IR injury in rats. Design:Animal study. Setting:Research laboratory. Subjects:Male Sprague-Dawley rats. Interventions:Animals were assigned to four experimental groups: 1) Sham rats underwent laparotomy without vascular occlusion and breathed air, 2) Sham-oxygen rats underwent laparotomy without vascular occlusion and breathed 100% oxygen, 3) IR rats underwent occlusion of the superior mesenteric artery and portal vein for 30 minutes and breathed air, and 4) IR group treated with oxygen (IR-O2)rats underwent IR and breathed 100% oxygen starting 10 minutes before and continued for the first 6 hours after reperfusion. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours after IR. Measurements and Main Results:In IR rats, breathing 100% oxygen resulted in a significant decrease in Parks injury score in the ileum (p < 0.05 from untreated IR rats). Rats treated with oxygen also demonstrated a significant increase in mucosal weight (p < 0.05) and mucosal DNA (p < 0.05) in the jejunum and ileum, and an increase in villus height (p < 0.01), and crypt depth (p < 0.05) in the ileum. Enterocyte proliferation (assessed by bromodeoxyuridine uptake) was significantly decreased in the jejunum and ileum in untreated IR rats. Oxygen therapy increased enterocyte proliferation in the ileum, and diminished both the apoptosis index and Bax gene expression in the jejunum and ileum (p < 0.05). Plasma thermochemiluminescence oxidizability assay revealed significantly higher thermochemiluminescence ratios in IR group treated with oxygen than in untreated IR rats (p < 0.05) at 6 hours postreperfusion suggesting a significantly lower prior in vivo molecular oxidation. Conclusions:Hyperoxia reduces small bowel injury, accelerates enterocyte turnover, and improves intestinal rehabilitation after IR.

A rare case of completely isolated duplication cyst of the alimentary tract.

A rare case of a gastrointestinal cystic duplication in a 7-day-old infant is described. The duplication diagnosed antenataly at 25 weeks of gestation was found during surgery to be separated from the gastrointestinal tract, hanging on a vascular pedicle, with no connection to the mesentery. The duplication was excised, and postoperative follow-up of 14 months was uneventful. The possible pathogenesis of this malformation is discussed.

Low-fat diet impairs postresection intestinal adaptation in a rat model of short bowel syndrome

BACKGROUND Low-fat diets (LFD) are utilized frequently in patients with short bowel syndrome (SBS). The purpose of this study was to investigate the effects of LFD on intestinal adaptation, enterocyte proliferation, and enterocyte cell death in a rat model of SBS. METHODS Adult male Sprague-Dawley rats were divided into 3 experimental groups: Sham-NC rats underwent bowel transection and reanastomosis and were fed normal chow (NC), SBS-NC rats underwent 75% small bowel resection and were fed NC, and SBS-rats were fed a low-fat diet (SBS-LFD). Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 14 after operation. RESULTS SBS-NC rats showed a significant increase (v Sham-NC) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. A significant 67% increase in crypt cell proliferation rate and 265% increase in villus enterocyte apoptosis was seen in the ileum of SBS-NC rats compared with control animals (P <.05). SBS-LFD animals showed lower ileal mucosal weight (29%; P <.05), jejunal crypt depth (20%; P <.05), and ileal villus height (21%; P <.05). A significant decrease in villus apoptosis in jejunum (74%; P <.05) and ileum (67%; P <.05) and a decrease in cell proliferation in ileum (35%; P <.05) was seen also after exposure to LFD compared with SBS-NC. CONCLUSIONS In a rat model of SBS, early LFD appears to inhibit parameters of intestinal adaptation. A possible mechanisms for this effect may be decreased cell proliferation. Decreased enterocyte loss via apoptosis, found in this study, may reflect a reduced number of enterocyte.

Oral insulin enhances intestinal regrowth following massive small bowel resection in rat.

Experimental studies have suggested that insulin (INS) plays an important role in small intestinal growth and development. In the present study we investigated the effect of oral INS on structural intestinal adaptation and enterocyte proliferation and loss via apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague–Dawley rats were divided into three experimental groups: sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-INS rats underwent bowel resection and were treated with oral INS given in the drinking water from the 3rd to the 15th postoperative day. Parameters of intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villous height, and crypt depth), enterocyte proliferation, and apoptosis were determined on day 15. SBS-INS rats demonstrated a significant increase (vs SBS rats) in jejunal and ileal overall bowel and mucosal weight, ileal mucosal DNA and protein, ileal villous height, and crypt depth. SBS-INS rats also showed an increased cell proliferation index in jejunum and ileum and decreased apoptotic index in jejunum compared to SBS animals. In conclusion, in a rat model of SBS, oral INS strongly enhances intestinal adaptation.Possible mechanisms may include increased cell proliferation and decreased enterocyte loss via apoptosis.

Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat

BackgroundArginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat.MethodsMale rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression.ResultsMTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels.ConclusionsTreatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.

Parenteral but Not Enteral Omega-3 Fatty Acids (Omegaven) Modulate Intestinal Regrowth After Massive Small Bowel Resection in Rats

BACKGROUND The purpose of the present study was to evaluate the effects of ω-3 fatty acids (Omegaven) on early intestinal adaptation in rats with short bowel syndrome (SBS). METHODS Male Sprague-Dawley rats were randomly assigned to 1 of 4 groups: sham rats underwent bowel transection; SBS rats underwent 75% bowel resection; SBS-O ω-3 rats underwent bowel resection and were treated with oral Omegaven given by gavage; and SBS-I ω-3 rats underwent bowel resection and were treated with Omegaven given intraperitoneally. Rats were killed on day 14. Parameters of intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depths, cell proliferation and apoptosis) were determined at time of death. Real-time polymerase chain reaction was used to determine the level of Bax and Bcl-2 messenger RNA (mRNA). Statistical analysis was performed using Kruskal-Wallis test followed by post hoc test, with P < .05 considered statistically significant. RESULTS Oral ω-3 supplementation did not significantly change intestinal regrowth. In contrast, parenteral ω-3 in rats that underwent resection resulted in higher bowel and mucosal weights, mucosal DNA and protein in ileum, villus height in ileum, crypt depth in jejunum and ileum, and greater rates of cell proliferation in jejunum and ileum compared with SBS animals. The initial decreased levels of apoptosis corresponded with the early decrease in Bax and increase in Bcl-2 mRNA levels. CONCLUSIONS Parenteral but not enteral Omegaven augments and accelerates structural bowel adaptation in a rat model of SBS. Increased cell proliferation and decreased apoptosis reflect increased cell turnover in Omegaven-treated animals.

Leptin affects intestinal epithelial cell turnover in correlation with leptin receptor expression along the villus-crypt axis after massive small bowel resection in a rat.

In this study, we examine the responsiveness of intestinal epithelial cell turnover to leptin (LEP) in correlation with leptin receptor (LEPr) expression along the villus-crypt axis in a rat with short bowel syndrome (SBS). Adult rats underwent either a 75% intestinal resection or a transection. SBS-LEP rats underwent bowel resection and were treated with LEP starting from the fourth postoperative day. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined at sacrifice. RT-PCR technique was used to determine Bax and Bcl-2 gene expression in ileal mucosa. Villus tips, lateral villi, and crypts were separated using laser capture microdissection. LEPr expression for each compartment was assessed by quantitative real-time PCR (Taqman). Treatment with LEP significantly stimulated all parameters of adaptation. LEPr expression in crypts significantly increased in SBS rats (vs Sham rats) and was accompanied by a significant increase in enterocyte proliferation and decreased apoptosis after LEP administration. A significant increase in LEPr expression at the tip of the villus in SBS rats was accompanied by decreased cell apoptosis. In conclusion LEP accelerated enterocyte turnover and stimulated intestinal adaptation. The effect of LEP on enterocyte proliferation and enterocyte apoptosis correlated with receptor expression along the villus-crypt axis.

Hypnosis for Postradiation Xerostomia in Head and Neck Cancer Patients: A Pilot Study

Xerostomia, the sensation of dry mouth, affects almost all patients who undergo radiotherapy for cancer in the head and neck area. Current therapies for xerostomia are inadequate, and the condition negatively impacts the quality of life. This prospective observational pilot study aimed to evaluate whether hypnosis could improve salivation and decrease xerostomia. Twelve patients with xerostomia after radiotherapy for head and neck cancer were assessed for severity of xerostomia symptoms and sialometry. They then received a single hypnosis session with specific suggestions to increase salivation. The session was recorded on a compact disk (CD), and the participants were instructed to listen to it twice a day for one month. Sialometry was repeated immediately after hypnosis. Validated xerostomia questionnaires were completed at one, four, and 12 weeks after hypnosis. A substantial overall improvement was reported by eight patients at 12 weeks (66%). The saliva flow rate increased on sialometry in nine patients following hypnosis (75%). There was no correlation between the magnitude of changes in the measured saliva flow rate and changes in subjective measures (Spearmans correlation coefficient r=0.134). Symptomatic improvement significantly correlated with the number of times the patients listened to the hypnosis CD (r=0.714, P=0.009). No adverse events were reported. The data from this small observational trial suggest that hypnosis may be an effective treatment for xerostomia. Confirmation in a larger randomized and controlled investigation is warranted.