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Ochratoxin A (OTA) is reported to cause intestinal damage following ingestion of contaminated foods. Tibetan kefir (TK) is a fermented dairy product that possesses antioxidant, anti-inflammatory, and gut microbiota-regulating properties. However, it is not clear if TK can alleviate OTA-associated intestinal toxicity. Here, we investigated whether TK can prevent OTA-induced intestinal barrier disruption in mice. To this end, OTA-fed mice were treated with sterile water (control) or TK by oral gavage once daily, for 3 weeks. The histological changes of ceca, the expression of tight junction proteins and mucins, and the levels of oxidative stress, inflammatory response, and gut microbiota were then assessed. Results revealed that treatment with TK reversed OTA-driven histopathological changes in the ceca, and was associated with increased cecal mucin levels. TK administration to OTA-treated mice significantly elevated the expression levels of tight junction proteins (claudin-1, zonula occludens-1, and occludin). Additionally, TK supplementation suppressed OTA-induced oxidative stress and reduced inflammation via the NF-κB signaling pathway in the ceca. Moreover, TK supplementation depleted harmful bacteria (e.g., Turicibacter and Desulfovibrio), while supporting short-chain fatty acids (SCFAs)-producing bacteria (e.g., Lachnospiraceae, Blautia, and Ruminococcus), which maintained the SCFAs levels. Taken together, our findings indicate that TK may emerge as a viable dietary strategy to prevent intestinal toxicity-based injuries., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: Competing interests: None declared.

A 34-year-old man who had been referred to our hospital was diagnosed with acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA), oral administration, was initiated. On day 25, he developed fever and respiratory distress with bilateral pulmonary infiltrates, suggesting differentiation syndrome (DS) caused by ATRA. These symptoms showed amelioration after discontinuing ATRA and initiating methylprednisolone. ATRA was re-started on day 29 at half the original dose because of residual APL blasts. The patient subsequently developed fever, severe stomatitis, and oropharyngeal ulcers, which persisted even after discontinuing ATRA. On day 48, he suddenly developed severe abdominal pain with free air, observable on an abdominal X-ray, and underwent emergency ileocecal resection. Pathological examination of the resected ileocecal intestines revealed multiple ulcers and perforations. No leukemic cell infiltration was observed. In this case, only ATRA was administered for APL treatment. These findings suggest that ileocecal ulcerations and perforations, as well as oropharyngeal ulcers, might have been caused by DS or ATRA. Furthermore, DNA typing of the HLA-B locus revealed that the patient had HLA-B51 associated with Behçet's disease. Therefore, hypercytokinemia with DS might have induced Behçet's disease-like symptoms, including stomatitis and ileocecal perforation, complications that are particularly observed in patients with HLA-B51.

Acute appendicitis is a common surgical diagnosis but several differential diagnoses exist and should be considered. Internal concealment is one such diagnosis. We present a case of a young man taken to the operating room with a preoperative diagnosis of complicated acute appendicitis. A ruptured caecum was encountered and several free-floating drug pellets were present. Attending doctors should consider this differential in the high prevalence areas and, whenever encountered, they should strongly consider early reporting., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Systemic lead poisoning may occur from ingested lead foreign bodies. Rarely, these may cause a retained appendolith. The risks of lead toxicity from these appendoliths, the time course of retention in the appendix, the rapidity of inhibition of heme synthesis, and the best approach to removal remain controversial. Fourteen days post-ingestion of a "handful" of lead shot, a 15-year-old male was admitted for elevated lead level; an x-ray showed aggregation of many pellets in the teen's appendix. A laparoscopic appendectomy was performed; examination of the removed appendix revealed greater than 50 retained pellets. An abdominal film obtained post-procedure showed removal of all but three of the pellets. Results from admission blood work found a blood lead level of 41 mcg/dL and free erythrocyte porphyrin (FEP) level of 114 μmol/mol heme (reference normal <70). After a short recovery the patient was discharged on succimer chelation therapy and on follow up, his lead level was <5 mcg/dL., (Copyright © 2012 Informa Healthcare USA, Inc.)

Background: Adhesion formation after abdominal surgery is a major cause of postoperative bowel obstruction, infertility, and chronic abdominal pain. In this study, we evaluated the effect of normal saline and methylene blue (MB) on postoperative adhesion formation in a rat cecum model., Methods: A total of 30 Wistar female rats in 2 treatment and 1 control groups underwent midline laparotomy and standardized abrasion of the visceral peritoneum. Normal saline and methylene blue were administrated intraperitoneally at the end of the surgical procedure in 2 treatment groups. Fourteen days after surgery, a re-laparotomy was performed for macroscopic and pathological assessment., Results: The adhesion grade and extent of the normal saline group was lower than control and MB groups in macroscopic assessment (P<0.05 for both). A comparison of adhesion stages in pathological assessment showed increment in abdominal adhesion by usage methylene blue 1% and demonstrated significant difference between MB and 2 other groups (P<0.05)., Conclusions: Administrated normal saline individually reduce the adhesion grade near cecum. Conversely, usage of methylene blue 1% may unpredictably increase risk of adhesion formation., (Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: Hemostatic agents are frequently used during abdominal surgery and some are linked to adhesion formation. We sought to evaluate the impact of several commonly used hemostatic agents on adhesion formation in a rat peritoneal model., Methods: In our study, Wister outbred rats underwent laparotomy and excision of a portion of their peritoneum to initiate adhesion formation process. One of six different hemostatic agents, namely, activated starch microspheres (Arista AH; Medafor Inc., Minneapolis, MN), glutaraldehyde activated collagen (BioGlue; Cryolife Inc., Kennesaw, GA), thrombin coated collagen microspheres (FloSeal; Baxter Inc., Deerfield, IL), thrombin activated fibrin polymer (Tisseel, Baxter), polyethylene glycol polymer (CoSeal, Baxter), or oxidized cellulose (Surgicel; Ethicon Inc., Somerville, NJ), was placed in the area of peritoneal defect. All animals were sacrificed on post-op day 7 and strength and extent of adhesion formation was determined. Histopathological examination of rat caecum was also performed., Results: Arista and CoSeal showed significantly lower adhesion formation than controls (P < 0.05). Higher adhesion scores were seen in BioGlue (P < 0.05) treated rats. Additionally, histopathologic examination showed that BioGlue caused statistically more inflammation and necrosis than controls (P < 0.05). Total adhesion score increased with residual amount of agent present at 7 d., Conclusions: Use of Arista and CoSeal may help in reducing peritoneal adhesions after intra-abdominal surgeries. Furthermore, there appears to be a relationship between the creation of inflammation and necrosis in tissues and the eventual formation of adhesions. This could aid in improving the design of these agents in the future.

Intussusception of the appendix is a rare occurrence. Due to the similarity of its symptoms with appendicitis, preoperative diagnosis of this condition is extremely difficult. In this report, we present appendiceal intussusception with histological melanosis coli that occurred in a patient on long-term anthranoid laxative use for chronic constipation. Melanosis coli in the appendiceal tissue, as an indicator of chronic laxative intake, may be a clue implying that the appendical exposure to hyperperistalsis for a long time in our case led to the intussusception. We conclude that colonoscopy may help in preoperative diagnosis of appendiceal intussusception in patients with suspicious appendicitis, particularly in those using laxative medication.

Purpose: To assess the rate of severe bowel complications during treatment with the anti-vascular endothelial growth factor monoclonal antibody bevacizumab., Methods and Materials: We performed a retrospective evaluation of bevacizumab-associated severe intestinal adverse events from our institutional database., Results: A total of 33 patients started treatment with bevacizumab at our institution during the first 6 months after its approval in Germany. Three patients (9%) presented with severe bowel complications: two with acute ischemic colitis and one with gastrointestinal perforation with a fatal outcome. All 3 patients had undergone radiotherapy directed to the pelvis before treatment with bevacizumab. None of the 30 patients without bowel complications had been pretreated with infradiaphragmatic irradiation. Histologic evaluation of bowel biopsies and resection specimens revealed severe ischemic bowel damage as the pathophysiologic background of the clinical findings., Conclusion: This report contributes to the pathophysiologic clarification of bevacizumab-induced bowel complications and points to a potentially increased risk of severe ischemic damage during treatment with bevacizumab in patients who have undergone previous radiotherapy.

We present a case of severe lower gastrointestinal bleeding due to appendiceal ulcer associated with intake of enteric coated aspirin. Urgent colonoscopy revealed the location and characteristics of the source of bleeding during the acute episode, allowing effective treatment through simple appendicectomy to be performed.

Background: Cecal perforation due to neutropenic colitis is a known and described side effect of many chemotherapy regimens. We present a case of a patient with gastric adenocarcinoma who developed spontaneous cecal perforation during chemotherapy without the classic pattern of typhlitis., Case Report: A 58-year-old woman was on chemotherapy for an adenocarcinoma of the gastric junction, when she developed a cecal perforation. There was neither evidence for leucopenia nor for typhlitis. Laparotomy was performed and cecostomy was established using the perforated bowel. Postoperative course was uneventful. The patient died from tumor progression 8 months after the diagnosis was made., Conclusion: There is no evidence for a connection between this event and chemotherapy treatment but neither can it be excluded. Even if unusual, colon toxicity could be a potential life-threatening complication associated with more drugs than usually thought.

Neutropenic colitis, characterized by neutropenia plus cecal and ascending colon inflammation, is a rare complication of chemotherapy in hematological malignancies and, less commonly, of medication used to treat other diseases (e.g., hyperthyroidism). We report a case of neutropenic colitis with cecal perforation in a 44-year-old woman treated with methimazole for hyperthyroidism. The patient had received subtotal thyroidectomy for hyperthyroidism in 1984 and recurrent hyperthyroidism was found in 1993. She was then treated with methimazole for almost 3 months, when sustained fever, diarrhea, weakness, and progressive abdominal pain developed. Due to the findings of peritonitis and neutropenia, she underwent emergent laparotomy. During the operation, chronic ulceration of the cecum with perforation was found and resection of the ileocecal segment and ileostomy were performed. Three months later, closure of the ileostomy with anastomosis of the ileocolostomy was performed. Her condition was stable during 9 years' follow-up. In conclusion, neutropenic enterocolitis has a broad spectrum of clinical presentations that require alertness in patients with neutropenia. When detected late, it may lead to bowel perforation and even mortality.

The aim of the study was to investigate the etiology of cecal and hepatic lesions in mice and rats after intravenous administration of gas-carrier contrast agents (GCAs). A modified fluorescein flowmetry technique and 24 h necropsy were used in mice (conventional and germ free), rats, and guinea pigs after GCA administration. Different diets and oral nonabsorbable antibiotics were used. Nonfluorescence, edema, congestion, hemorrhage, and mucosal erosion in cecum and colon and nonfluorescent areas in the liver were observed from 16 min after GCA administration in conventional mice on standard diet. Numerous gas bubbles (>50 microm) were observed in the vasculature around the nonfluorescent areas of cecum and colon and in mesenteric vessels draining to the portal vein. Acute inflammation, edema, hemorrhage, and ulceration of the cecum and colon and liver necrosis were seen 24 h after GCA administration in conventional mice on standard diet. When mice were maintained on either a diet with glucose as the only carbohydrate source or on a standard diet supplemented with antibiotics, uniform fluorescence and no organ lesions were observed after GCA administration. Uniform fluorescence and no organ lesions were observed in germ-free mice, rats, and guinea pigs dosed with GCAs and in control animals (mice, rats, and guinea pigs) dosed with sucrose. The results indicate that intravascular growth of GCA microbubbles occurs in the cecal and colonic wall of mice, leading to occlusive ischemia and necrosis in these intestinal segments and secondary gas embolisation in the liver. Transmural gas supersaturation in the cecal wall may explain the intravascular bubble growth in mice.

Introduction: Acute typhlitis is usually associated with severe immunosuppressive conditions. Initially described as closely associated with infantile myeloid leukaemia, its incidence increased along the last decade., Design: retrospective review., Patients: 12 immunodepressed patients affected of acute typhilis in our hospital between 1994 and 2001. Suspected diagnosis was established by clinical symptoms and abdominal CT findings, and was confirmed with pathological finding in the surgical specimen. Clinical and radiological diagnosis, treatment, complications and survival of patients are discussed., Results: 3 patients with a previous diagnosis af acute myeloid leukemia, 2 patients with non-Hodgkin lymphoma, 2 patients with aplastic anaemia, one patient with AIDS, and 4 patients with kidney transplantation were included in our study. Prednisone, cyclosporine, Ara-C and vincristine were the most frequently involved drugs. Most frequent clinical findings included abdominal pain, fever, nausea-vomiting and abdominal distension. CT diagnosis revealed caecum and colic involvement with rarefaction of pericaecal fat. Medical treatment was successful in only 33% of all patients, the other patients requiring a surgical procedure including right hemicolectomy with or without intestinal anastomosis. Mortality reached 58.3 per cent, representing multiorganic sepsis the main cause of death., Conclusions: although early diagnosis of acute typhlitis bears a better prognosis, mortality rates are up 50 % in spite of an established treatment.

Introduction: Enterocolic phlebitis is an entity characterized by ischemic injury of the gastrointestinal tract caused by thrombophlebitis of the mesenteric veins without arterial involvement or systemic disease., Exegesis: We report a case of enterocolic phlebitis in a 57-year-old female treated by rutoside, revealed by intestinal obstruction related to a pseudotumoral lesion of the caecum., Conclusion: This case adds to the four cases of enterocolic phlebitis under rutoside already reported in the literature, suggesting a possible involvement of this drug in this rare disease.

Objectives: Cyclic administrations of dextran sulphate sodium (DSS) alternating with distilled water usually induce chronic colitis after a few weeks. In order to obtain stable chronic colitis (without recovery or relapse) in a few days, a new continuous DSS treatment was tested and characterized. Short-chain fatty acids (SCFAs), which remain poorly documented in experimental colitis, were also investigated., Methods: Thirty-six Sprague-Dawley rats were treated with 5% DSS for 7 days (DI) followed by 3% DSS for 7 days (DM) or 14 days (DF). Control rats received only water. Inflammatory injuries in the caecum and the colon were assessed by macroscopic (colon length, caecum weight, damages score) and histological parameters. SCFAs (acetate, propionate, butyrate) were quantified individually in caecal, proximal and distal contents., Results: Macroscopic and histological observations revealed that this continuous DSS treatment induced acute inflammation (DI) followed rapidly by chronic active colitis. The latter was uncommonly predominant in the caecum and the distal colon, and was also associated with some fermentative disturbances. Caecal SCFA concentrations decreased with DSS at DI and DM. The molar ratio of caecal butyrate increased with DSS. Acetate decreased in the colon while propionate increased., Conclusion: This new DSS treatment is able to induce in a few days stable chronic inflammation with caecal and distal predominant injuries, and mild fermentative caeco-colonic alterations. This model could contribute to the study of potential anti-inflammatory effects of prebiotics.

The chronic toxicity of clinafloxacin, a fluoroquinolone antibacterial agent, was evaluated in multiple strains of mice and rats. In 5 separate studies, mice and rats that were orally administered up to 1,000 mg/kg of clinafloxacin from 9 to 104 weeks developed dose-related cecal dilatation and deaths that were attributable to cecal torsion. Cecal rupture was observed in association with torsion. Although cecal dilatation is commonly observed in rodents given antibacterials such as fluoroquinolones, cecal torsion has not been a reported sequelae to dilatation.

Injection of Brown-Norway rats with mercuric chloride (HgCl2) activates a T helper type 2 (Th2) autoimmune response, with production of a number of autoantibodies and vasculitis primarily affecting the gut. Glucocorticoids have been shown to suppress Th1 and to promote the development of Th2-type responses. Conversely dehydroepiandrosterone (DHEA) promotes Th1 responses with suppression of Th2 responses. This study set out to define the role of these hormones in this animal model. Rats were adrenalectomized (Adx) with no steroid replacement (n = 11), Adx with basal steroid replacement given by a 25 mg corticosterone pellet inserted subcutaneously (n = 13), or sham-Adx (n = 14) prior to administration of HgCl2. In both groups of Adx animals there was a delay in the production of immunoglobulin E (IgE) and serum concentrations on day 9 were marginally lower (P = 0.035, repeated measures ANOVA). All of the animals Adx with no steroid replacement and two Adx animals with steroid replacement died between 10 and 14 days after HgCl2 challenge. There was no difference in the severity of caecal vasculitis between the groups. A significant increase in adrenal size was noted following administration of HgCl2. Administration of subcutaneous DHEA implants (100 mg and 200 mg) had no significant effect on IgE concentrations or severity of vasculitis. These observations do not support the hypothesis that corticosterone and DHEA play a central role in setting the Th1/Th2 balance in this experimental Th2-mediated autoimmune disease; in contrast with the Th1-mediated autoimmune disease experimental allergic encephalomyelitis where corticosterone plays a key role in immunoregulation.

Sodium chloride transport across isolated cecum mucosa was investigated in normal rats and rats with adaptive cecum growth induced by dietary polyethylene glycol (PEG). The normal cecum absorbed Cl in excess of Na with a small short-circuit current (ISC). Dietary adaptation led to large equivalent increments of Na and Cl net absorption without adequate ISC change. Inhibitor studies (mucosal amiloride 10(-3) and 10(-4) M; mucosal 4, 4-diisothiocyanatostilbene-2,2-disulfonic acid 5 x 10(-5) M; serosal furosemide 10(-3) M; serosal ouabain 10(-3) M) suggested that normal cecal NaCl absorption involves electroneutral Na/H and Cl/HCO3 exchange at the apical and Na-K-ATPase-mediated exit across the basolateral cell membrane. Dietary adaptation stimulates the loosely coupled antiports and possibly activates a small serosally located NaCl cotransport. Comparative histology showed flattening of all tissue layers and widening of crypts in PEG animals. Crypt widening may facilitate ion access to underutilized transport sites and, at least in part, explain the increased absorption of the enlarged cecum.

A case is described of an elderly woman who developed an obstructing barolith in the sigmoid colon following a barium enema. Colonic ischaemia developed in the proximal colon. Predispositions and prevention of baroliths are discussed.

Background: The treatment of acute leukemia in childhood has been increasingly successful. Concurrently, severe leukemia-related gastrointestinal complications have become more common., Methods: We evaluated the findings of the abdominal ultrasound (US) examinations of 52 children with acute lymphoblastic leukemia (ALL) who had severe clinical symptoms indicating infection or abdominal complication during chemotherapy treatment or after the cessation of such treatment and assessed the impact of these findings on patients' subsequent treatment and survival., Results: Our study presents ten cases of typhlitis with a prevalence of 9%, all of which were rapidly diagnosed by US and had a favourable outcome. We also found focal intra-abdominal parenchymal lesions in six children, five of them due to fungal infection and one due to leukemic infiltration. Several other intra-abdominal pathologies significant for the patients' treatment are also reported., Discussion: We believe that abdominal US is a useful, rapid, safe, and accurate imaging method for children with ALL suspected to suffer from leukemia- or chemotherapy-related gastrointestinal complications. More invasive imaging methods are seldom needed., Conclusions: According to our results, abdominal US gives the necessary information in most of the cases and provides prompt diagnosis, which may prevent possible fatal complications.

Kayexalate (Roxane Labs, Columbus, OH) in sorbitol is commonly administered by the oral and rectal route for the treatment of hyperkalemia in patients with renal failure. It is believed to have minimal toxicity because it functions as a cation exchanger and is not absorbed. We herein report on a patient who developed identical serpiginous ulcers in the stomach and the terminal ileum after the use of Kayexalate. We believe that this drug could have significant gastrointestinal toxicity in specific patient groups and suggest tentative guidelines, both for the identification of such patients and for the safer use of Kayexalate in these circumstances.

Mercuric chloride (HgCl2) induces a T cell-dependent autoimmune syndrome in Brown-Norway (BN) rats characterized by a humoral response, tissue injury with an accumulation of CD8+ and CD4+ T cells, and an increase in tissue IL-4 mRNA and serum IgE suggesting Th2 cell activation. In other models of autoimmune disease, CD8+ cells act in both anti- and pro-inflammatory capacities, suggesting that functionally distinct CD8+ populations exist in vivo. The effect of treatment with OX8, a depleting anti-CD8 MoAb, on the initiation of HgCl2-induced autoimmunity was assessed in two experiments in a total of 20 BN rats, and compared with 20 animals treated with a control MoAb or PBS. OX8 significantly depleted peripheral blood CD8+ lymphocytes, had no effect on HgCl2-induced anti-collagen or myeloperoxidase antibodies, nor on the incidence or severity of caecal vasculitis. The severity of HgCl2-induced arthritis was significantly reduced in OX8-treated animals; median peak score reduced from 7.5 to 3.0 (experiment 1) and from 7.0 to 4 (experiment 2) (P = 0.009, Mann-Whitney U-test). OX8 treatment also exacerbated the early rise in HgCl2-induced IgE and induced a significant rise in plasma interferon-gamma (IFN-gamma), suggesting that CD8+ cells may have a regulatory influence on Th cell populations. These data provide direct evidence that CD8+ cells may act in a proinflammatory capacity in both this model of autoimmunity and the pathogenesis of inflammatory arthritis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a variety of gastrointestinal side effects. Effects on the large intestine have been reported with increasing frequency. Recognition of NSAID-induced colonic lesions has been confounded by variable clinical presentations, variable pathologic findings, and unfamiliarity of this entity among clinicians. We have recently seen three cases of NSAID-induced cecal ulcerations in patients undergoing right colectomy. A correct preoperative diagnosis was not made in our patients, one of whom presented with an acute abdomen and two in whom there was an inability to rule out carcinoma. The gross, radiographic, and histologic findings in each case consisted of a characteristic transverse ulceration with thin diaphragm-like scarring. NSAID-induced cecal ulcers can have a variety of presentations to the general surgeon, are likely to be misdiagnosed preoperatively, but may be recognized based on characteristic gross features evident by radiography and colonoscopy, along with a careful history. Review of recent literature suggests that laparotomy can be avoided when diagnosis is considered, but operation is indicated for complications, such as hemorrhage, obstruction, or perforation, and when carcinoma cannot be adequately excluded.

Benign ulcers of the colon are a rare source of colorectal bleeding. The present case report describes a woman who experienced several episodes of bleeding from an NSAID-induced ulcer of the caecum. The differential diagnosis of colonic ulcers is discussed.

The phosphodiesterase inhibitor oxpentifylline (OXP) has a number of potentially important immunomodulatory actions which include a selective inhibition of the Th1 subset of CD4+ cells in vitro and inhibition of tumor necrosis factor (TNF)-alpha mRNA transcription. In vivo, it has a dramatic protective effect against experimental allergic encephalomyelitis. In this animal model, tissue injury is associated with both a Th1 response and with TNF-alpha production, either of which could be targets for the protective action of OXP. In an attempt to clarify the relative importance of the Th cell subsets and TNF-alpha in pathogenesis, we investigated the effect of OXP on a Th2 model of T cell-dependent disease, mercuric chloride (HgCl2)-induced autoimmunity in the Brown Norway rat. The effects of OXP on the Th1:Th2 response, TNF-alpha mRNA transcription in spleen and ankle joints, and on the incidence and severity of arthritis and cecal vasculitis have been examined and the effects in vivo have been compared with those of a soluble TNF receptor-IgG1 fusion protein (sTNFR) that neutralizes rat TNF-alpha. In two separate experiments, OXP significantly enhanced unstimulated levels of splenic interleukin-4 (IL-4) mRNA (median 62%, of an artificial IL-4 mRNA construct, vs. 36.5% in controls) and in one experiment, exaggerated the total IgE response to HgCl2. OXP inhibited HgCl2-induced TNF-alpha mRNA transcription in spleen and ankle joints. In three separate experiments, OXP had a significant protective effect against arthritis, with the mean incidence reduced from 100% to 30% and mean peak score reduced from 7.2 to 2.59 (experiments 1 and 2). The protection against arthritis was indistinguishable from that produced by sTNFR. There was no such protection against cecal vasculitis with either OXP or sTNFR. These results demonstrate that OXP induces a shift towards a Th2 response, inhibits TNF-alpha mRNA transcription locally in joint and systemically in spleen, and has a protective effect against arthritis similar to that produced by sTNFR in the HgCl2-treated BN rat. We conclude that TNF-alpha is a critical cytokine in the pathogenesis of arthritis but not cecal vasculitis in this model, and that inhibition of TNF-alpha transcription is the most important mode of action of OXP in this situation. OXP may be a potential therapeutic agent in the treatment of other arthritides, such as human rheumatoid arthritis, in which TNF-alpha has been implicated in pathogenesis.

Unlabelled: The most common risk factors for the development of necrotizing enterocolitis (NEC) are prematurity and enteral feeding. Most models of NEC involve ischemic insult resulting in generalized necrosis, different from the classical ileocecal predilection of NEC. This anatomic predisposition is explained by dysmotility of immature gut, leading to bacterial overgrowth in the terminal ileum and colon. Infant formula containing lactose as the sole carbohydrate source overwhelms partially developed lactase activity, allowing enteric bacteria to ferment excess carbohydrate to short-chain fatty acids, decreasing intraluminal gut pH and predisposing to mucosal injury. Impaired clearance of intraluminal contents exacerbates this effect. In the present study the authors used a model of NEC, originally developed in rabbits and based on analysis of intestinal contents of NEC babies, modified and adapted here to neonatal piglets, the gastrointestinal tract of which more closely resembles the human neonate., Method: Piglets < 3 days old and 2 weeks old were laparotomized. Loops created from the distal ileum to the proximal colon were injected with isoosmolar acidified casein solution or 0.9% saline. Segments were harvested 3 hours later, sectioned for H&E, and graded from 0 (intact villi) to 4 (transmural necrosis)., Results: Acidified casein-induced damage included areas of necrosis, submucosal edema, inflammatory cell infiltrate, and lymphatic distension. In younger animals, lesions were more pronounced (3.25 +/- 0.13 for the < 3-day-old v 2.43 +/- 0.14 for the 2-week-old piglets; P < .005)., Conclusion: The authors believe that this piglet NEC model most closely approximates human NEC because it incorporates two of the most common risk factors: dysmotility (by creating intestinal loops) and enteral feeding (by intraluminal injection of acidified casein).

We report mycobacterial granulomatous inflammation in the ulcerated caecum of rats that received indomethacin. Two groups of male rats were treated with dietary indomethacin 3 mg/kg/day or untreated diet for 3 weeks. Six out of 8 indomethacin treated rats showed both ulceration and inflammation of the caecal mucosa. Two of the rats showing caecal ulceration also showed distinct granulomatous inflammation of the caecal mucosa and acid-fast bacilli were identified within granulomata. None of the other indomethacin treated or control rats contained acid-fast bacilli within caecal tissue sections but they were present, in the same sections, within the lumen of most rats in both groups. Polymerase chain reaction analysis identified the mycobacterial 65 kDa GroEL gene within control and granulomatous caecal tissue. In a repeat of indomethacin administration to a third group of rats, culture of both non-granulomatous caecal tissue (containing histologically identified luminal acid-fast bacilli) and faecal samples for mycobacteria was negative.

This case report concerns a 30-year-old man who survived a 4.2 g diltiazem overdose. He sustained vasoplegic shock with a junctional escape rhythm which required high doses of norepinephrine and epinephrine. Among other complications, ileus with paralytic intestinal pseudo-obstruction developed on day three. Cecal distention was demonstrated by abdomen computed tomodensitometry. The ileus resolved on day seven following the poisoning. Diltiazem plasma concentrations were determined during the first three days. The possible role of other medications, activated charcoal and sufentanil, is noted.

Background: Patients on nonsteroidal anti-inflammatory drugs can develop curious intestinal fibrotic diaphragms., Methods: Groups of rats received indomethacin mixed into a powdered diet at 3 mg.kg/day for 6 and 12 weeks and 6 mg.kg/day for up to 6 weeks. In an attempt to reproduce a human dosing regimen, another group of rats, for a total of 30 weeks, received consecutive periods of indomethacin at 3 mg.kg/day for 12 weeks, 4.5 mg.kg/day for 1 week, 6 mg.kg/day for 1 week, control diet for 6 weeks, 4.5 mg.kg/day for 2 weeks and finally, a control diet for a healing period of 8 weeks. Control rats received powdered diet alone. At termination, the small and large intestines were examined macroscopically and histologically., Results: Indomethacin caused microcytic anaemia, hypoalbuminaemia, small intestinal ulceration, caecal ulceration and inconspicuous raised mucosal lesions in the caecum that histologically showed submucosal fibrosis with disruption and thickening of the apical muscularis mucosae. No control rats showed any abnormality., Conclusion: These fibrotic lesions of the rat caecum resemble human diaphragms and may arise from healed caecal ulcers.