Efficacy and Safety of Subcutaneous Neostigmine for Ileus, Acute Colonic Pseudo-obstruction, or Refractory Constipation.

BACKGROUND: Neostigmine is traditionally administered intravenously for treatment of acute colonic pseudo-obstruction (ACPO), though use is associated with administration constraints and adverse effects. OBJECTIVE: To evaluate whether an alternative route of administration for neostigmine via subcutaneous (SQ) delivery is safe and effective in a broad cohort of medical and surgical patients. METHODS: This multicenter, retrospective observational study included adult patients administered SQ neostigmine for ileus, ACPO, or refractory constipation. Efficacy indicators were time to first bowel movement (BM) following initiation of the medication, total SQ neostigmine dose administered to produce a BM, and administration of a rescue intervention to produce a BM. Safety events evaluated were cardiac arrest, bradycardia, bronchospasm requiring intervention, nausea requiring intervention, or severe salivation, lacrimation, or diarrhea. RESULTS: A total of 182 patients were eligible for inclusion. The most commonly utilized dosing strategy of neostigmine was 0.25 mg SQ 4 times daily. The median time to first BM following initiation of SQ neostigmine was 29.19 hours (interquartile range = 12.18-56.84) with a median dose administered before first BM of 1.25 mg. Three patients (1.65%) experienced an adverse drug event leading to drug discontinuation, with 2 developing bradycardia that resolved with drug discontinuation alone. CONCLUSIONS: SQ neostigmine may be reasonable for management of ileus, ACPO, or refractory constipation, though use should be avoided in patients with new-onset heart block, a history of second-degree heart block, or following bowel resection with primary anastomosis. Despite the low incidence of adverse drug events observed, monitoring for bradycardia with telemetry may be considered.

A case of refractory intestinal Behçet's disease treated with tocilizumab, a humanised anti-interleukin-6 receptor antibody.

We describe a young female patient who had refractory intestinal Behçet's disease that responded to tocilizumab, a humanised anti-interleukin-6 receptor antibody. The patient had suffered from long disease activity courses and was treated with multiple medications, and the disease became refractory when immunosuppressants (e.g., thalidomide, sulfasalazine and azathioprine) were limited for poor remission, methylprednisolone pulse therapy, cyclophosphamide, and biological agents (e.g., adalimumab or infliximab) were restricted due to side effects after administration. Therefore, tocilizumab was considered as a therapeutic option and the symptoms resolved during 9 months of administration. Tocilizumab may be a good choice for intestinal Behçet's disease refractory to conventional treatment.

The Impact of Resveratrol on Oxidative Stress Induced by Methotrexate in Rat Ileum Tissue: Evaluation of Biochemical and Histopathological Features and Analysis of Gene Expression.

OBJECTIVE: The aim of this study was to assess the impact of resveratrol (RST) on oxidative stress induced by methotrexate in rat ileum tissue. MATERIALS AND METHODS: Twenty-four rats were divided into 4 groups with 6 in each group. Each rat was orally administered the following every day for 30 days: group 1 (MTXG), methotrexate (MTX; 5 mg/kg); group 2 (RMTXG), MTX (5 mg/kg) plus RST (25 mg/kg/day); group 3 (RSTG), RST alone (25 mg/kg/day), and group 4 (controls), distilled water. After the rats had been sacrified, the ilea were removed for the assessment of malondialdehyde (MDA), total glutathione (tGSH) and glutathione peroxidase (GSH-Px). Gene expression analyses for interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) were also performed. Hematoxylin and eosin-stained paraffin-embedded sections of the ileum were analyzed under a light microscope and the findings were recorded. Statistical analyses of the data were performed using one-way ANOVA. RESULTS: The administration of MTX in group 1 yielded a higher level of MDA (8.33 ± 2.5 µmol/g protein, p < 0.001) and lower levels of tGSH (0.97 ± 0.29 nmol/g protein) and GSH-Px (5.22 ± 0.35 U/g protein, p < 0.001) compared to the other groups. MTX also increased IL-1ß (40.33 ± 5.43 gene expression levels), TNF-α (6.08 ± 0.59) and MPO gene expression (9 ± 1.41) in group 1 compared to the controls (11.33 ± 2.07, 2.15 ± 0.33 and 3.43 ± 0.48, respectively, p < 0.001). The impact of RST on IL-1ß, TNF-α and MPO gene expression induced by MTX was observed as a reversal of these findings (p < 0.05). Severe inflammation, damage to the villus epithelium and crypt necrosis was observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the RMTXG group. CONCLUSION: In this study, ileal damage caused by MTX was inhibited by RST.

Changes of Crohn's disease phenotype over time.

Background - Crohn's disease is a clinically heterogeneous condition. Our aim was to identify the phenotype evolution of Crohn's disease over time according to the Montreal Classification and to precise predictive factors of the need for immunosuppressant treatment or surgery. Methods - We included Crohn's disease patients who were followed up for at least 5 years. We excluded patients who were lost to follow up before five. Patients were classified according to the Montreal classification for phenotype at diagnosis and five years later. The evolution of phenotype over time and the need for surgery, immunosuppressive or immunomodulatory drugs were evaluated. Results - One hundred twenty consecutive patients were recruited: 70 males and 50 females. At diagnosis, 68% of patients belong to A2 as determined by the Montreal classification. Disease was most often localized in the colon. The disease location in Crohn's disease remains relatively stable over time, with 93.4% of patients showing no change in disease location. Crohn's disease phenotype changed during follow up, with an increase in stricturing and penetrating phenotypes from 6% to 11% after 5 years. The only predictive factor of phenotype change was the small bowel involvement (OR=3.7 [1.2-7.6]). During follow-up, 82% of patients have presented a severe disease as attested by the use of immunosuppressive drugs or surgery. The factors associated with the disease severity were: small bowel involvement (L1), the stricturing (B2) and penetrating (B3) phenotypes and perineal lesions (OR=17.3 [8.4-19.7]; 12 [7.6-17.2]; 3[1.7-8.3] and 2.8 [2.2-5.1] respectively), without association with age, sex or smoking habits. Conclusion - Crohn's disease evolves over time: inflammatory diseases progress to more aggressive stricturing and penetrating phenotypes. The ileal location, the stricturing and penetrating forms and perineal lesions were predictive of surgery and immunosuppressant or immunomodulatory treatment.

A case of ileocecal actinomycosis treated by preoperative antibiotic treatment to reduce mass size followed by surgical resection.

A 65-year-old woman presented to a nearby clinic with a painful mass in the right lower abdominal region. She was suspected of having an appendiceal tumor on abdominal computed tomography (CT) and was referred to our hospital for surgery. Blood testing revealed increased inflammatory markers. Contrast-enhanced abdominal CT revealed a mass with poorly defined margins in the ileocecal region, which was adjacent to the external iliac vessels. A barium enema revealed unilateral wall deformities in the cecum through to the terminal ileum, whereas lower gastrointestinal endoscopy showed no clear epithelial tumor component. The patient was clinically diagnosed with ileocecal actinomycosis and treated with high-dose penicillin G. On day 15 of treatment, contrast-enhanced abdominal CT showed a reduction in mass size. On day 26, right hemicolectomy (D3) with combined resection of the external iliac vein (which could not be separated from the mass) was performed. Pathological examination revealed granulation tissue with granules of actinomyces, with filamentous bacteria detected by Grocott staining. With no evidence of malignancy, the final diagnosis of ileocecal actinomycosis was made. This report presents a case of clinically suspected ileocecal actinomycosis treated by preoperative antibiotic treatment to reduce mass size, followed by surgical resection.

Resveratrol Reduces Morphologic Changes in the Myenteric Plexus and Oxidative Stress in the Ileum in Rats with Ischemia/Reperfusion Injury.

BACKGROUND: Intestinal ischemia/reperfusion injury can be caused by surgical procedures and inflammatory bowel disease. It is normally associated with the increased production of free radicals and changes in the enteric nervous system. AIMS: Given the antioxidant and neuroprotective properties of resveratrol, the present study assessed its influence on oxidative stress in the intestinal wall and the morphology of myenteric neurons in the ileum of rats subjected to ischemia/reperfusion. METHODS: Resveratrol was orally administered daily at a dose of 10 mg/kg for 5 days. Changes in the ileum response to ischemia after 45 min were investigated followed by 3 h reperfusion. Lipoperoxide and carbonylated protein levels, and the activity of the antioxidant enzymes glutathione reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase were measured following ischemia/reperfusion injury. RESULTS: The density and morphometry of the general neuronal population, nitrergic neurons and glial cells, and morphometry of VIP varicosities in the ileum were also studied. Lipoperoxide and carbonylated protein levels were 171 and 40% higher during the ischemia/reperfusion, respectively, compared to control cohorts, and resveratrol attenuated these values. The glutathione ratio was 64% lower during ischemia/reperfusion, compared to control cohorts. Resveratrol increased the reduced/oxidized glutathione ratio, attenuated the changes in the activity of the antioxidant enzymes and the detrimental morphologic changes caused by ischemia/reperfusion in the general neuronal population and nitrergic neurons. CONCLUSIONS: Oral treatment with resveratrol reduced the oxidative stress in the ileum and attenuated the morphologic changes that occurred in the myenteric plexus of the ileum in rats subjected to ischemia/reperfusion.

The Effect of Midazolam on Decreasing the Duration of Intussusception Hydrostatic Reduction in Children.

BACKGROUND AND OBJECTIVE: The use of sedative medications may be effective in the success and facilitation of the intussusception non-surgical treatment. Therefore, the purpose of this study was to examine the effect of midazolam on decreasing the duration of intussusception hydrostatic reduction in children. MATERIALS AND METHODS: In a double-blind clinical trial, 32 children were diagnosed with ileocolic intussusception based on sonographic findings, were studied and randomly divided into two groups. After obtaining written informed consent from the parents, 5 minutes before reduction, an intravenous Midazolam at the concentration of 1.0 mg/kg (up to 3 mg) was infused, and then barium reduction was performed under fluoroscopy guideline. In the control group, sterile water was injected as placebo and the remaining reduction steps were performed compared with the experiment group. RESULTS: Of 16 patients that received Midazolam, 15 patients demonstrated successful reduction; and of 16 patients that received distilled water, only 11 patients showed successful reduction (P=0.07). The mean duration of a successful reduction in the Midazolam group and placebo was 34.8±11.35 and 32.73±19.2 min, respectively (P=0.733). CONCLUSIONS: The use of Midazolam as a benzodiazepine with known sedative and muscle relaxant effects can increase the success rate of enema reduction in intussusception.

Microscopic polyangiitis complicated with ileal involvement detected by double-balloon endoscopy: a case report.

BACKGROUND: Microscopic polyangiitis is characterized by pauci-immune, necrotizing small-vessel vasculitis and an anti-neutrophil cytoplasmic antibody-associated vasculitis. Although gastrointestinal involvement in microscopic polyangiitis is not rare, endoscopic observation of it is extremely rare. To the best of our knowledge, this is the first case report of small intestinal involvement in microscopic polyangiitis detected and followed up by double-balloon endoscopy. CASE PRESENTATION: A 70-year-old Japanese woman was transferred to our hospital for close examination of suspected small intestinal lymphoma. Retrograde double-balloon endoscopy revealed various forms of ulcers with redness and edema in the ileum. Histological findings suggested ischemic changes. Because mononeuritis multiplex and a fever spike appeared later, vasculitis was suspected. The perinuclear anti-neutrophil cytoplasmic antibody titer was elevated. Nerve biopsy results suggested vasculitis. From these findings, microscopic polyangiitis was diagnosed. It was suggested that microscopic polyangiitis caused the intestinal involvement. Intravenous pulse cyclophosphamide and oral predonisolone were started. After treatment, perinuclear anti-neutrophil cytoplasmic antibodies decreased to the normal range. Retrograde double-balloon endoscopy after treatment showed ulcer scars and no ulcer. CONCLUSION: The cause of gastrointestinal involvement in microscopic polyangiitis is ischemia due to vasculitis. It is difficult to diagnose small-vessel vasculitis by endoscopic biopsy. Although histological evidence of microscopic polyangiitis is important, the treatment should not be delayed by repeating the biopsy, because such delay can result in adverse sequela.This case report shows that microscopic polyangiitis should be considered as a differential diagnosis when small intestinal changes like those in the present case are observed by endoscopy.

Dietary long-chain PUFA enhance acute repair of ischemia-injured intestine of suckling pigs.

Infant formula companies have been fortifying formulas with long-chain PUFA for 10 y. Long-chain PUFA are precursors of prostanoids, which stimulate recovery of intestinal barrier function. Supplementation of milk with PUFA increases the content of arachidonic acid (ARA) in enterocyte membranes; however, the effect of this enrichment on intestinal repair is not known. The objective of these experiments was to investigate the effect of supplemental ARA on intestinal barrier repair in ischemia-injured porcine ileum. One-day-old pigs (n = 24) were fed a milk-based formula for 10 d. Diets contained no PUFA (0% ARA), 0.5% ARA, 5% ARA, or 5% EPA of total fatty acids. Following dietary enrichment, ilea were subjected to in vivo ischemic injury by clamping the local mesenteric blood supply for 45 min. Following the ischemic period, control (nonischemic) and ischemic loops were mounted on Ussing chambers. Transepithelial electrical resistance (TER) was measured over a 240-min recovery period. Ischemia-injured ileum from piglets fed 5% ARA (61.0 ± 14%) exhibited enhanced recovery compared with 0% ARA (16 ± 14) and 0.5% ARA (22.1 ± 14)-fed pigs. Additionally, ischemia-injured ileum from 5% EPA (51.3 ± 14)-fed pigs had enhanced recovery compared with 0% ARA-fed pigs (P < 0.05). The enhanced TER recovery response observed with ischemia-injured 5% ARA supplementation was supported by a significant reduction in mucosal-to-serosal flux of (3)H-mannitol and (14)C-inulin compared with all other ischemia-injured dietary groups (P < 0.05). A histological evaluation of ischemic ilea from piglets fed the 5% ARA showed reduced histological lesions after ischemia compared with the other dietary groups (P < 0.05). These data demonstrate that feeding elevated levels of long-chain PUFA enhances acute recovery of ischemia-injured porcine ileum.

Budesonide use in pediatric Crohn disease.

BACKGROUND AND AIM: Budesonide (BUD) is being used in pediatric Crohn disease (CD) because it is believed to have the potential to reduce corticosteroid-related toxicity; however, few data are available describing its use. The aim of the present study was to describe BUD use in an inception cohort of pediatric patients with CD. METHODS: Data were derived from the prospective Pediatric IBD Collaborative Research Group Registry established in 2002 in North America. Use of BUD in children with CD was examined. RESULTS: BUD was used in 119 of 932 (13%) of children with newly diagnosed CD, with 56 of 119 (47%) starting BUD ≤ 30 days of diagnosis (26/56 with ileum and/or ascending colon [IAC] disease). BUD was used as monotherapy (9%), in combination with 5-aminosalicylates (77%), or in combination with immunomodulators (43%). Forty-three percent (24/56) went on to receive conventional corticosteroid at some point following their first BUD course. For the 63 of 119 (53%) who started BUD beyond the diagnosis period, 51 of 63 (81%) also received prednisone, with BUD used as a means of weaning from prednisone in 17 of 63 (27%). Patients with IAC disease who received BUD ≤ 30 days of diagnosis were just as likely to have received conventional corticosteroids by 1 year as were those who did not receive BUD ≤ 30 days of diagnosis. Two-thirds (77/119) of patients received BUD for ≤ 6 months. CONCLUSIONS: BUD is being used among pediatric patients newly diagnosed as having CD, although the majority does not have disease limited to the IAC. BUD monotherapy was rare, and further data are required to better define the role of BUD in the treatment of pediatric CD.

The role of steroids in children with multiple recurrences of intussusception.

We describe the case of a boy who had 9 recurrences of intussusception, for which no pathological lesion at the leadpoint was identified. A contrast follow-through study revealed a follicular/nodular mucosal pattern, particularly prominent in the terminal ileum and caecum. Patients with multiple recurrences usually have an identifiable lesion at the leadpoint, but sometimes recurrences may be due to lymphoid hyperplasia, as presumed in our case. No further recurrences occurred after a two month tapering course of oral prednisolone.

Early Combined Immunosuppression May Be More Effective for Reducing Complications in Isolated Colonic- vs Ileal-Dominant Crohn Disease.

BACKGROUND: We assessed whether differential efficacy of early combined immunosuppression (ECI) in comparison with conventional management (CM) is present in patients with Crohn disease (CD) according to disease location. METHODS: In this posthoc analysis of the Randomized Evaluation of an Algorithm for Crohn's Treatment trial, the effect of ECI vs CM modified by disease location (isolated-colonic vs ileal-dominant) in terms of time to first complication (hospitalization, surgery, or disease-related complications-presence of a new abscess, fistula, or stricture; serious worsening of disease activity; extraintestinal manifestations) was analyzed using a marginal Cox proportional hazard model to account for cluster randomization. Factors adjusted included practice size, country, and other covariates selected in a backward logistic regression analysis with the first composition as outcome and P < 0.10. RESULTS: Of the 1969 patients with CD, 435 had isolated colonic CD (ECI n = 257, CM n = 178) and 1534 had ileal CD (ECI n = 817, CM n = 717). Over 24 months there was a significant differential impact for ECI vs CM for reducing the risk of a CD-related complication between patients with colonic CD and ileal CD (colonic CD hazard ratio [HR] = 0.51; 95% CI, 0.30-0.85 vs ileal CD HR = 0.79; 95% CI, 0.57-1.10; P = 0.033). No difference was identified between ECI vs CM for reducing the risk of surgery (colonic HR = 0.52 vs ileal HR = 0.74; P = 0.468) or hospitalization (colonic HR = 0.77 vs ileal HR = 0.83; P = 0.806). CONCLUSIONS: In this posthoc analysis of the Randomized Evaluation of an Algorithm for Crohn's Treatment trial, symptom-based ECI was associated with greater efficacy for reducing the risk of CD-related complications in patients with colonic disease location relative to ileal disease location.

Oxytocin or social housing alleviates local burn injury in rats.

BACKGROUND: Thermal injury may cause distant organ inflammation and multiorgan failure. Oxytocin (OT), a nonapeptide, modulates the immune and inflammatory processes. MATERIALS AND METHODS: To investigate the effects of oxytocin on burn-induced tissue injury, Sprague-Dawley rats were subjected to a partial thickness burn. Immediately after burn, half of the burned rats were placed single in the cages, while others were caged in groups. All the rats then were treated with either OT (5 microg/kg, s.c) or saline twice daily for 5 d. The control rats had no burn injury and received no treatments. On day 5, the rats were decapitated, tissue and serum samples were obtained to score the severity of damage and to assay TNF-alpha levels. RESULTS: Burn trauma resulted in oxidative ileal damage, as evidenced by increased apoptotic rate, increased neutrophil recruitment, and enhanced lipid peroxidation. OT treatment depressed the TNF-alpha level and alleviated dermal degeneration, while attenuating ileal damage. Although a higher degree of skin damage was observed in the animals kept isolated following burn injury, keeping the rats in groups did not affect the level of TNF-alpha or the severity of dermal or ileal injury, but abolished the burn-induced elevations in ileal lipid peroxidation and myeloperoxidase activity. Moreover, OT treatment reduced the ileal apoptosis when applied to rats housed in groups, while the treatment did not alter apoptotic ratio in the isolated rats. CONCLUSION: Oxytocin can be considered as a potential agent in treating burn-induced distant organ injury.

Invasive aspergillosis of the small bowel in an infant with acute myeloid leukemia and intestinal obstruction.

Acute myeloid leukemia was diagnosed in an infant with fever and pancytopenia. Intestinal obstruction was present at diagnosis and laparotomy performed after failure of conservative management demonstrated leukemic infiltration of the resected terminal ileum. Fever and intestinal obstruction persisted, necessitating a second ileal resection, which revealed invasive aspergillosis. Subsequent retrospective analysis identified occasional fungal hyphae in the initial resection specimen. With the combination of intensive chemotherapy and aggressive prolonged antifungal therapy the child survived. Invasive aspergillosis may unusually present at nonpulmonary sites at initial presentation of acute leukemia. Microbiological or histological diagnosis is needed to guide aggressive appropriate management.

Hereditary angio-oedema as a rare cause of small-bowel obstruction.

A 52-year-old man with known hereditary angio-oedema (HAE) presented with a 2-day history of progressive severe abdominal pain, distension, nausea, vomiting and constipation. CT of his abdomen and pelvis showed small-bowel obstruction and ascites. HAE is a rare autosomal dominant disorder caused by a C1 esterase deficiency and involves episodic oedema of subcutaneous and mucosal tissues. It commonly affects the face and limbs, causing deformity; the respiratory tract, causing life-threatening laryngeal swelling; and the gastrointestinal tract, causing small-bowel obstruction. An infusion of a C1 esterase inhibitor was given to the patient. His symptoms resolved within 6 hours, and a repeat CT showed complete resolution 24 hours later. Small-bowel obstruction in HAE is often misdiagnosed, leading to ineffective treatment and unnecessary surgery. Therefore, this should be suspected in patients with HAE presenting with an acute abdomen, and clinicians should understand the unique treatment required.