Bowel necrosis

Support for the PAF-cytokine feedback system is not only provided by our in vitro data demonstrating that PAF antagonists drastically reduce TNF-stimulated PMN superoxide generation, but also by the in vivo observations of Sun and Hsueh [324] who have shown that the PAF antagonist SRI 63-119 prevents TNF-induced bowel necrosis in the rat. 

Gastric and upper small bowel necrosis have been described after oral ingestion of massive amounts of concentrated saline (1 kg of sodium chloride in 660 ml of water) as an emetic. 

Two women were investigated for cramping abdominal pain and bloody diarrhea (22). In only one did the episodes completely disappear after withdrawal of sumatriptan. The other underwent an exploratory laparotomy and right hemicolectomy for transmural bowel necrosis. 

PAF also has potent effects on many other biological systems. For example, PAF induces hepatic phosphoinositide turnover and glycogenolysis which is accompanied by glucose release into the plasma. PAF has also been implicated as a mediator of ischemic bowel necrosis since it can independently induce lesions morphologically similar to those present during human necrotizing enterocolitis. Furthermore, the role of PAF or a PAF-like lipid as an endogenous antihypertensive substance is currently under intense experimental scrutiny. 

Fig. 1.36a-c. Pneumatosis intestinalis in a 1-week-old infant. Anteroposterior (a) and lateral (b) plain radiographs show small and large bowel loops sharply outlined by collections of gas in bowel wall. Most of these collections of gas are linear, indicating a submucosal location, c Surgical image of the same patient demonstrates diffuse bowel necrosis... 

Most important in these cases is to exclude conditions that are life-threatening for the patient. As intestinal malrotations may lead to bowel ischemia, which may subsequently lead to bowel necrosis, the patient s life is at risk when less than 3 in. of small bowel remain (Andrassy and Mahour 1981). 

The preferred reduction technique is either that of the air enema under fluoroscopic guidance or of air or hydrostatic enema under ultrasound guidance. The only absolute contra-indication to attempted enema reduction is full thickness bowel necrosis (which will present with features of shock and peritonitis) or if there is imaging evidence of perforation with free air. 

Human tumor necrosis factor (TNF) (Fig. 1) is a hormone-like proinflammatory peptide belonging to the group of cytokines. It is mainly produced by cells of the immune system in response to infection, inflammation, or cell damage. Disregulated TNF is an important factor in many pathological situations, like sqDsis, rheumatoid arthritis, inflammatory bowel disease (Crohn s disease), and Cachexia. The cytotoxic activity of TNF is of interest in development of new antitumoral strategies. 

Clinical signs associated with widespread pancreatic inflammation and necrosis include marked epigastric tenderness, abdominal distention, hypotension, and low-grade fever. In severe disease, bowel sounds are diminished or absent. Dyspnea and tachypnea are signs of acute respiratory complications. 

Gastrointestinal diseases Inflammatory bowel disease, nontropical sprue, subacute hepatic necrosis... 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Komatsu M, Kobayashi D, Saito K, Furuya D, Yagihashi A, Araake H, Tsuji N, Sakamaki S, Niitsu Y, Watanabe N. Tumor necrosis factor-alpha in serum of patients with inflammatory bowel disease as measured by a highly sensitive immuno-PCR. Clin Chem 2001 47(7) 1297-1301. 

Traditional endoscopic and surgical procedures provide whole tumor samples well suited for microscopic examination and analysis in the pathology laboratory. The use of whole tissue tumor biopsies for proteomic studies has, however, raised several important issues that have been well demonstrated in CRC [9]. These include cellular heterogeneity in the different bowel parietal layers (mucosa, submucosa, muscularis mucosa, serosa) that may or may not be infiltrated, epithelial cell diversity in the mucosa itself, tissue infiltration by inflammatory cells such as lymphocytes, contamination with other body fluids, and protein degradation following tumor necrosis. In fact, epithelial cell content was found to vary between 9 and 67% in whole biopsies of normal mucosa and between 7 and 95% in tumor biopsies [10]. This study clearly demonstrates the likelihood of large cellular variation between tissue samples. 

Two remarkable successes of cytokine therapy are the treatment of multiple sclerosis with interferon-p and the treatment of rheumatoid arthritis and inflammatory bowel disease with tumor necrosis factor-a inhibitors. 

Sandborn, W.J. Hanauer, S.B. Antitumor necrosis factor therapy for inflammatory bowel disease a review of agents, pharmacology, clinical results, and safety. Inflamm. Bowel Dis. 1999, 5, 119-133. 

Amidotrizoate enemas are still sometimes used to treat meconium ileus or constipation, and it is important to give intravenous fluids so as to avoid dehydration. Hypomagnesemia can also occur (150). Osmotic effects lower in the gastrointestinal tract have even led to distention and cecal perforation (151). Stasis of amidotrizoate in dilated loops of bowel can cause inflammatory changes or necrosis (152,153). 

After rectal and oral administration, intestinal ulcers and necrosis have occnrred (13,19). Several cases affecting the large bowel have been reported and critically ill and nremic patients are at particular risk. 

In another case, colonic necrosis presented as an acute abdomen within 24 hours of administration of sodium polystyrene sulfonate in sorbitol (23). After prompt surgical resection of the necrotic transverse colon there was rapid recovery of bowel function. 

The possible involvement of CB2 receptors in inflammatory bowel disease has been hypothesised on the basis of recent in vitro studies indeed, cannabinoids exert an inhibitory effect on the expression of tumour necrosis factor (TNF)-a-induced interleukin-release from a human colonic epithelial cell line HT-29, and this effect was reversed by the CB2 receptor antagonist SR144528 (Ihenetu et al. 

ESR erythrocyte sedimentation rate IBD inflammatory bowel disease NSAID nonsteroidal anti-inflammatory drug TPMT thiopurine S-methyltransferase TNF-a tumor necrosis factor-alpha... 

Any disorder that results in necrosis of skeletal muscle cells (i.e., rhabdomyolysis) can result in the release of large amounts of intracellular phosphorus into the systemic circulation. This condition is frequently associated with acute renal failure and thus severe hyperphosphatemia may develop due to increased endogenous phosphorus release coupled with decreased renal phosphorus excretion. Bowel infarction, malignant hyperthermia, and severe hemolysis are also conditions that may increase endogenous release of phosphorus. 

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