Gastrointestinal and hepatic manifestations of Sjogren syndrome.

Sjogren syndrome (SS) is an autoimmune disease that affects exocrine glands and therefore may affect the gastrointestinal system, from the mouth, esophagus, and bowel to the liver and pancreas. Oral involvement in SS is mainly characterized by dryness, with a wide spectrum of symptoms, from mild-to-severe xerostomia with dysgeusia and tooth decay. The dysphagia, although common, does not correlate with the reduced salivary flow rate or the dysmotility that may be present. Dyspepsia, found in up to 23% of patients, may be associated with gastritis, reduced acid production, and antiparietal cell antibodies, but rarely pernicious anemia. Pancreatic involvement, although rare, includes pancreatitis and pancreatic insufficiency. The most common causes of liver disease are primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatitis C virus (HCV). Although abnormal liver tests are found in up to 49% of patients, they are usually mild. Although sicca syndrome, abnormal histology of the salivary glands, and abnormal sialograms are common in primary biliary cirrhosis, the antibodies to Ro/SSA or La/SSB antigens are infrequent. Xerostomia, sialadenitis, abnormal salivary flow rates, and abnormal Schirmer test in HCV vary widely among the studies, although the antibodies to Ro/SSA or La/SSB are only 1%. Several studies show that HCV is in saliva, although how this may impact sicca syndrome or SS in HCV is unclear. SS as a disease of exocrine glands affects many parts of the gastrointestinal system.

Gastrointestinal manifestations of leukemia.

Gastrointestinal (GI) manifestations of leukemia occur in up to 25% of patients at autopsy, generally during relapse. Its presence varies with the type of leukemia and has been decreasing over time due to improved chemotherapy. Gross leukemic lesions are most common in the stomach, ileum, and proximal colon. Leukemia in the esophagus and stomach includes hemorrhagic lesions from petechiae to ulcers, leukemic infiltrates, pseudomembranous esophagitis, and fungal esophagitis. Lesions in the small and large bowel are usually hemorrhagic or infiltrative. Infiltration of lymphoreticular organs, mainly spleen, liver, and lymph nodes, is more prominent in chronic than acute leukemia. Neutropenic enterocolitis, a necrotizing process involving the cecum, ascending colon, and terminal ileum, is increasing in incidence due to greater intensity of chemotherapy. Distension of bowel leads to mucosal breaches, permitting entry of organisms that grow profusely in the absence of neutrophils. Ischemic necrosis follows, leading to perforation and/or peritonitis. Patients present with fever, abdominal pain, diarrhea, nausea, vomiting, abdominal distension and tenderness. Ultrasound and computed tomography scans show thickening of the bowel wall. Treatment is supportive with surgery for necrosis and perforation. The main GI causes of death in leukemia are hemorrhage, infection, and necrotizing enterocolitis.

Utilization survey of a rural creek fishery in central Alabama.

A one-year angler intercept survey was conducted on Choccolocco Creek, a rural, limited access tributary to the Coosa River in northeastern Alabama. The purpose of the survey was to collect data and information about the behaviors and fish consumption habits of the recreational anglers who fish there. Nine survey locations were included in the stratified sampling plan, and sampling occurred throughout daylight hours, on weekdays and weekends/holidays, during all four seasons of the year. Surveys were completed on a total of 101 survey days between June 28, 2008 and June 27, 2009.(6) Seventy-two anglers were observed fishing during the survey period, and 52 (72%) of those individuals agreed to participate in the survey. Based on the information collected by the survey clerks, the angler population fishes the Creek between 1 and 54 times per year, with an average frequency of seven trips per year. The average number of months fished was three months per year, with a range of one to nine months. Only 15% of the anglers who participated in the survey (eight individuals) had succeeded in catching fish by the end of their trips, and only four of those individuals (8%) had retained any of the fish they had caught for consumption. Reasons provided for not retaining fish were that they either only fished for sport, did not catch enough fish to eat, or the fish they caught were too small to keep. Because so few anglers used and harvested fish from the resource, fish consumption rates could not be determined with a high degree of confidence. However, from these limited data it was estimated that the three anglers for whom consumption rates could be estimated had annualized average daily fish consumption rates of 0.14, 0.44, and 7.9 grams per day (g/day). The majority of anglers traveled less than 10 miles to fish the Creek. It was estimated that a total population of 173 anglers use the Creek each year. The results of this survey indicated that Choccolocco Creek is a local fishery that is not heavily used by area residents.

Gastrointestinal and hepatic manifestations of systemic lupus erythematosus.

In this review of the gastrointestinal (GI) and hepatic manifestations of systemic lupus erythematosus (SLE), 180 articles from the English literature, found using a medline search from January 1965 to December 2010, were examined. Vasculitis may cause ulcerations, bleeding, stricture formation, and perforation from ischemia and infarction. Otherwise, GI symptoms, occurring in about 50% of patients, are usually mild. Esophageal dysmotility may result in heartburn, regurgitation, and dysphagia. Occasionally, pneumatosis cystoides intestinalis may develop, sometimes associated with benign pneumoperitoneum. Patients are prone to salmonella bacteremia, presenting more commonly with fever and abdominal pain than with diarrhea. Intestinal pseudoobstruction usually is found with active lupus serology, preferentially involving small rather than the large bowel. Protein-losing enteropathy, characterized by diarrhea, edema, and hypoalbuminemia, can be the initial presentation of SLE. Malabsorption with a prevalence of 9.5% is occasionally associated with celiac disease. Pancreatitis, with an annual incidence of 0.4 to 1/1000, has an overall mortality of 27% that is decreased with corticosteroid therapy. Acute and chronic ascites may be due to lupus peritonitis or to associated diseases, such as pancreatitis, nephrotic syndrome, heart failure, or infections. Abnormal liver function tests may be due to steatosis from lupus or from corticosteroid therapy. Only about 10% of patients with autoimmune hepatitis have lupus. Up to 4.7% of patients with SLE have chronic active hepatitis correlating strongly with the presence of antibody to ribosomal P protein. SLE can involve the entire GI tract and the liver. Treatment with corticosteroids, cytotoxic agents, and/or immunosuppressants is often successful.

Gastrointestinal and hepatic manifestations of rheumatoid arthritis.

Rheumatoid arthritis (RA), characterized by inflammation of the synovium and surrounding structures, has a prevalence of 0.5-1%. Rheumatoid vasculitis (RV) is an inflammatory condition of the small- and medium-sized vessels that affects up to 5% of patients with RA with intestinal involvement in 10-38% of these cases. Clinically apparent RV of the gastrointestinal (GI) tract, while rare, is often catastrophic, resulting in ischemic ulcers and bowel infarction. Vasculitis of the colon may present as pancolitis clinically similar to ulcerative colitis. Rectal biopsies that include submucosal vessels are positive for vasculitis in up to 40% of cases. Abnormal esophageal motility in RA may result in heartburn and dysphagia. Chronic atrophic gastritis may be associated with hypergastrinemia and hypo- or achlorhydria, promoting small bowel bacterial overgrowth. RA is the most common cause of secondary amyloidosis with GI symptoms in 22% of affected patients. Although amyloid is usually found in the liver, it is rarely evident clinically. Felty's syndrome occurs in less than 1% of patients with RA and is characterized by neutropenia and splenomegaly. The liver may be involved with portal fibrosis or nodular regenerative hyperplasia. Liver histology is abnormal in 92% of RA patients at autopsy, although the changes are usually mild without associated hepatomegaly. Drug-induced liver disease may occur with aspirin, sulfasalazine, and methotrexate. Significant liver damage is rare if the drug is discontinued or the patient is properly monitored. RA can affect both the GI tract and the liver; changes are usually mild except with RV.

Gastrointestinal and hepatic complications of sickle cell disease.

Sickle cell disease (SCD) is an autosomal recessive abnormality of the beta-globin chain of hemoglobin (Hb), resulting in poorly deformable sickled cells that cause microvascular occlusion and hemolytic anemia. The spleen is almost always affected by SCD, with microinfarcts within the first 36 months of life resulting in splenic atrophy. Acute liver disorders causing right-sided abdominal pain include acute vaso-occlusive crisis, liver infarction, and acute hepatic crisis. Chronic liver disease might be due to hemosiderosis and hepatitis and possibly to SCD itself if small, clinically silent microvascular occlusions occur chronically. Black pigment gallstones caused by elevated bilirubin excretion are common. Their small size permits them to travel into the common bile duct but cause only low-grade obstruction, so hyperbilirubinemia rather than bile duct dilatation is typical. Whether cholecystectomy should be done in asymptomatic individuals is controversial. The most common laboratory abnormality is an elevation of unconjugated bilirubin level. Bilirubin and lactate dehydrogenase levels correlate with one another, suggesting that chronic hemolysis and ineffective erythropoiesis, rather than liver disease, are the sources of hyperbilirubinemia. Abdominal pain is very common in SCD and is usually due to sickling, which resolves with supportive care. Computed tomography scans might be ordered for severe or unremitting pain. The liver typically shows sickled erythrocytes and Kupffer cell enlargement acutely and hemosiderosis chronically. The safety of liver biopsies has been questioned, particularly during acute sickling crisis. Treatments include blood transfusions, exchange transfusions, iron-chelating agents, hydroxyurea, and allogeneic stem-cell transplantation.

The thyroid and the gut.

Thyroid disease is common, and its effects on the gastrointestinal system are protean, affecting most hollow organs. Hashimoto disease, the most common cause of hypothyroidism, may be associated with an esophageal motility disorder presenting as dysphagia or heartburn. Dyspepsia, nausea, or vomiting may be due to delayed gastric emptying. Abdominal discomfort, flatulence, and bloating occur in those with bacterial overgrowth and improve with antibiotics. Reduced acid production may be due to autoimmune gastritis or low gastrin levels. Constipation may result from diminished motility, leading to an ileus, megacolon, or rarely pseudoobstruction. Ascites in myxedema is characterized by a high protein concentration. Graves' disease accounts for 60% to 80% of thyrotoxicosis. Hyperthyroidism is accompanied by normal gastric emptying with low acid production, partly due to an autoimmune gastritis with hypergastrinemia. Transit time from mouth to cecum is accelerated, resulting in diarrhea. Steatorrhea is due to hyperphagia and stimulation of the adrenergic system. Diarrhea in medullary carcinoma of the thyroid (MCT) may be due to elevated calcitonin, prostaglandins, or 5-hydroxyindoleacetic acid. Ileal or colonic function may be abnormal. The esophagus may be compressed by benign processes, but more often by malignancies. MRI and CT scans are the best diagnostic modalities. The gastrointestinal manifestations of thyroid disease are generally due to reduced motility in hypothyroidism, increased motility in hyperthyroidism, autoimmune gastritis, or esophageal compression by a thyroid process. Symptoms usually resolve with treatment of the thyroid disease.

The parathyroids and the gut.

This review discusses gastrointestinal manifestations of parathyroid diseases. Parathyroid hormone is the primary regulator of calcium physiology. Hypoparathyroidism can be idiopathic, hereditary, or secondary to surgery in the neck. Hyperparathyroidism is usually from adenomas or hyperplasia. Hypoparathyroidism is associated with steatorrhea that may improve with medium-chain triglycerides, correction of the hypoparathyroidism, or administration of vitamin D. Hyperparathyroidism results in constipation because of reduction in neuromuscular excitability by high calcium levels. According to old literature, the incidence of peptic ulcer disease (PUD) in patients with hyperparathyroidism is 9% compared with autopsy rates of 4% to 5%. Any association is difficult to prove today, as hyperparathyroidism is usually mild due to early detection of cases through routine automated measurements of calcium. In addition, PUD is less prevalent now than before the advent of proton pump inhibitors. The presence of ulcers or ulcer symptoms may correct in some patients after parathyroidectomy, suggesting an association. The incidence of pancreatitis in patients with primary hyperparathyroidism ranges from 1.5% to 12% and may be because of the hypercalcemia. Complicating the issue is secondary hyperparathyroidism in response to hypocalcemia from pancreatitis. Pancreatitis may improve in some individuals after parathyroidectomy. Pancreatitis may follow parathyroid surgery because of an acute rise in calcium levels with manipulation of the parathyroid glands or to a blunted response of calcitonin-producing cells from fatigue. Parathyroid diseases have a few distinct effects on the gut: steatorrhea in hypoparathyroidism, and constipation, PUD, and pancreatitis in hyperparathyroidism.

Interleukin 21 up-regulates perforin-mediated cytotoxic activity of human intra-epithelial lymphocytes.

Human intra-epithelial lymphocytes (IELs) are predominantly T-cell receptor-alphabeta(+) (TCR-alphabeta(+)) CD8(+) CD45RO(+) memory T cells located between intestinal epithelial cells. They respond to a greater extent to stimulation with interleukin (IL)-15 than to CD3/TCR triggering, suggesting that they react to the cytokine milieu in their local environment rather than to cognate antigen. A newly described member of the gammac cytokine family, IL-21, has potent antitumor effects. As IELs resemble lymphocytes infiltrating neoplastic lesions, their response to IL-21 may be relevant in vivo. Here, IL-21 was shown to increase perforin-mediated cytotoxicity and serine esterase release by IELs. This IL-21-mediated up-regulation occurred without changes in IEL survival or cell division. Interestingly, the effects of IL-21 occurred without increased phosphorylation of signal transducer and activator of transcription (STAT)1, STAT3, STAT4, STAT5, extracellular signal-regulated kinase (ERK), or p38. IL-21 had no effect on Fas ligand (FL)- or tumour necrosis factor-alpha (TNF-alpha)-mediated cytotoxicity, but it down-regulated IL-15-stimulated expression of CD25 and CD94, indicating that it has both positive and negative actions. This functional profile is unique to human IELs, emphasizing that they are a distinct compartment of lymphocytes and that IL-21 may promote their role in tumour immunosurveillance.

Antibody to tropomyosin isoform 5 and complement induce the lysis of colonocytes in ulcerative colitis.

OBJECTIVES: Tropomyosins (TMs) are cytoskeletal microfilament proteins present in all eukaryotic cells. Human TM isoform 5 (hTM5) is the predominant isoform in colonic epithelial cells. Antibodies against hTM5 are found both in the sera and in the mucosa of patients with ulcerative colitis (UC) but not Crohn's disease (CD). We investigated whether anti-hTM5 autoantibodies are pathogenic. METHODS: Normal-appearing colonic mucosal biopsy specimens were incubated with autologous serum. After 45 min, deposition of the complement component C3b was identified by indirect immunofluorescence assay (IFA). Additional specimens were incubated with autologous serum fixed in formalin, and their architecture was examined by hematoxylin and eosin (H&E) staining. RESULTS: For 79% of UC patients, autologous serum caused C3b staining along the colonic epithelium. Recombinant hTM5 or anti-hTM5 monoclonal antibody blocked serum-induced C3b deposition. Immunoglobulin G (IgG) antibody and affinity-purified anti-hTM5 IgG antibody from UC sera with complement caused C3b deposition, indicating specificity of hTM5 as an autoantigen. When analyzed by H&E staining, sera obtained from 71% of UC patients caused a significant loss of epithelium. This process was inhibited by Fc fragments, indicating that it is complement mediated. With medium, normal, or CD serum, there was no C3b deposition or morphological changes of the colonic epithelium, indicating disease specificity. The ileal mucosa was not affected by UC sera, suggesting specificity for the colon. In UC mucosa, expression of hTM5 increased. CONCLUSIONS: hTM5 acts as an autoantigen in UC. hTM5-specific IgG autoantibody in sera from UC patients induces C3b deposition and destruction of colonic epithelial cells, suggesting a direct pathogenic effect. If used as a diagnostic test to distinguish UC from CD, IFA would have 79% sensitivity and 100% specificity. Development of blocking antibodies may lead to novel therapies.

Gastrointestinal manifestations of Behçet's disease.

Behçet's disease is a rare vasculitis diagnosed by the presence of recurrent oral ulcers and two of the following: genital ulcers, typical eye lesions, typical skin lesions, and positive pathergy test. It is most commonly seen in countries along the ancient silk road from Eastern Asia to the Mediterranean Basin. Young adults between the second and fourth decades of life are mainly affected, with abdominal pain being the most common symptom. The ileocecal region is most commonly affected, with ulcerations that may penetrate or perforate. Rarely, the esophagus and stomach may have ulcerations. Bowel wall thickening is the most common finding on computed tomography (CT) scan. Pathology shows a vasculitis mainly involving the small veins or, alternatively, nonspecific inflammation. Corticosteroids, with or without other immunosuppressive drugs, are used for severe eye disease. Their use in intestinal disease is largely empirical. Surgery may be required for perforation. Behçet's disease runs a chronic, unpredictable course with exacerbations and remissions which decrease in frequency and severity over time. Death is mainly due to major vessel disease and neurological involvement.

Dissection of spontaneous cytotoxicity by human intestinal intraepithelial lymphocytes: MIC on colon cancer triggers NKG2D-mediated lysis through Fas ligand.

Human intestinal intraepithelial lymphocytes (IELs), which are T-cell receptor alphabeta+ CD8+ T cells located between epithelial cells (ECs), are likely to participate in the innate immune response against colon cancer. IELs demonstrate spontaneous cytotoxic (SC) activity specifically directed against EC tumours but not against other solid tumour types. The aim of this study was to dissect out the mechanism of SC activity, focusing on the interaction of NKG2D on IELs with its ligands [major histocompatibility complex (MHC) class I chain-related protein (MIC) and UL16 binding protein (ULBP)] found mainly on EC tumours. A novel series of events occurred. The NKG2D-MIC/ULBP interaction induced Fas ligand (FasL) production and FasL-mediated SC activity against HT-29 cells and MIC-transfectants. Tumour necrosis factor-alpha and interferon-gamma, produced independently of this interaction, promoted SC activity. The immune synapse was strengthened by the interaction of CD103 on IELs with E-cadherin on HT-29 cells. Neither T-cell receptor nor MHC class I was involved. While the HT-29 cells were destroyed by soluble FasL, tumour necrosis factor-alpha and interferon-gamma, the IELs were resistant to the effects of these mediators and to FasL expressed by the HT-29 cells. This unidirectional FasL-mediated cytotoxicity of IELs against HT-29 cells, triggered through NKG2D, is unique and is likely to be a property of those CD8+ tumour-infiltrating lymphocytes that phenotypically resemble IELs.

Massive interleukin-12-induced interferon-gamma production by interleukin-15-stimulated lamina propria lymphocytes followed by down-regulation of the interleukin-12 receptor.

The intestinal mucosal immune response must differentiate between harmless foreign antigens and pathogens, a distinction that may depend upon changes in the cytokine milieu. A key cytokine in the adaptive immune response is interleukin-12 (IL-12), secreted by antigen-presenting cells (APC) immediately after encounter with a pathogen. IL-12 is important in the priming and polarization of naïve T cells. Here, we show that IL-12 and IL-15 direct human intestinal lamina propria lymphocytes (LPL) in the absence of T-cell receptor engagement to secrete extremely high amounts of interferon-gamma (IFN-gamma), greater than with any other stimulus. The functional synergy of IL-12 with IL-15 surprisingly operates independently of signal transducer and activator of transcription 1 (STAT1), STAT3, STAT4, or STAT5 phosphorylation and occurs during transcription. Four-colour immunofluorescence showed that IL-12 receptor beta1 is found on the CD4+ T cells expressing intracytoplasmic IFN-gamma. Importantly, IL-12 receptors beta1 and beta2 are not up-regulated by IL-12, unlike findings using antigen-specific T cells, and are lost over time. This study demonstrates the early and massive IFN-gamma response of LPL to IL-12 and IL-15, providing the tools to deal with a pathogen. The down-regulation of IL-12 receptors may curtail any excess damaging inflammation.

Gastrointestinal involvement in polyarteritis nodosa.

Polyarteritis nodosa (PAN) is a necrotizing, focal segmental vasculitis that affects predominantly medium-sized arteries in many different organ systems. It is associated with hepatitis B virus (HBV) in about 7% of cases, a decline from about 30% before the mandatory testing of blood products and the widespread vaccination programs. HBV PAN is an early postinfectious process. The hepatitis is silent in most cases, with mild transaminase level increases in 50% of patients. Gastrointestinal involvement occurs in 14% to 65% of patients with PAN. Postprandial abdominal pain from ischemia is the most common symptom. When transmural ischemia develops, there may be necrosis of the bowel wall with perforation, associated with a poor prognosis. Liver involvement occurs in 16% to 56% of patients, although clinical manifestations related to liver disease are quite rare. Acalculous gangrenous cholecystitis may develop owing to arteritis involving the wall of the gallbladder. Microaneurysms on arteriography or computed tomography angiography are characteristic of PAN, but are seen in other conditions. Tissue biopsy may confirm the diagnosis, although involvement is segmental. Corticosteroids are used for non-HBV PAN with cyclophosphamide added for severe disease. For PAN related to HBV, a 2-week course of corticosteroids is begun, with plasma exchanges and an antiviral agent. Corticosteroids and cyclophosphamide have improved patient outcome so that the 1-year survival rate is now about 85%.

Gastrointestinal and hepatic manifestations of sarcoidosis.

Sarcoidosis is a multisystem disease characterized by noncaseating granulomas in the affected organs, including skin, heart, nervous system, and joints. Diagnosis of sarcoidosis is generally based upon a compatible history, demonstration of granulomas in at least two different organs, negative staining and culture for acid fast bacilli, absence of occupational or domestic exposure to toxins, and lack of drug-induced disease. Involvement of the hollow organs is rare. Rather than being due to sarcoidosis, some reported mucosal lesions may simply have incidental granulomas. Extrinsic compression from lymphadenopathy can occur throughout the gastrointestinal tract. The stomach, particularly the antrum, is the most common extrahepatic organ to be involved, while the small bowel is the least common. Liver involvement frequently occurs and ranges from asymptomatic incidental granulomas to portal hypertension from granulomas in the portal triad, usually with relatively preserved liver function. CT scans show hepatosplenomegaly and adenopathy, followed in frequency by focal low-attenuation lesions of the liver and spleen. Ascites is usually a transudate from right heart failure (because of pulmonary hypertension) or portal hypertension (because of biliary cirrhosis). Rarely, an exudative ascites may occur from studding of the peritoneum with nodules. Pancreatic involvement presents as a mass, usually in the head or a diffusely firm, nodular organ. Corticosteroids should be instituted when organ function is threatened, usually lungs, eyes, and central nervous system. Their role in the treatment of hepatic sarcoidosis is unclear. The overall prognosis is good although most patients will have some permanent organ impairment. Cardiac and pulmonary diseases are the main causes of death.

Hypoxic liver injury.

Hypoxic liver injury is defined as a massive, but transient, increase in serum transaminase levels due to an imbalance between hepatic oxygen supply and demand in the absence of other acute causes of liver damage. It typically occurs in elderly individuals with right-sided congestive heart failure and low cardiac output. Precipitating factors include arrhythmias or pulmonary edema. Symptoms include weakness, shortness of breath, and right upper quadrant pain. Less commonly, hypoxic liver injury is seen in patients with severe hypoxemia or septic shock. Characteristically, the transaminase level is elevated 20-fold but normalizes rapidly over several days. Imaging studies reveal hypoechoic or hypodense lesions that resolve completely with reversal of the initiating event. Treatment and prognosis depend on the underlyIng disease.

Derivation of human health-based ambient water quality criteria: a consideration of conservatism and protectiveness goals.

Under the terms of the Clean Water Act, criteria for the protection of human health (Human Health Ambient Water Quality Criteria [HHWQC]) are traditionally derived using equations recommended by the US Environmental Protection Agency (USEPA) that include parameters for exposure assessment. To derive "adequately protective" HHWQC, USEPA proposes the use of default values for these parameters that are a combination of medians, means, and percentile estimates targeting the high end (90th percentile) of the general population. However, in practice, in nearly all cases, USEPA's recommended default assumptions represent upper percentiles. This article considers the adequacy of the exposure assessment component of USEPA-recommended equations to yield criteria that are consistent with corresponding health protection targets established in USEPA recommendations or state policies, and concludes that conservative selections for exposure parameters can result in criteria that are substantially more protective than the health protection goals for HHWQC recommended by USEPA, due in large part to the compounding effect that occurs when multiple conservative factors are combined. This situation may be mitigated by thoughtful selection of exposure parameter values when using a deterministic approach, or by using a probabilistic approach based on data distributions for many of these parameters.

Gastrointestinal involvement in spinal cord injury: a clinical perspective.

Bowel problems occur in 27% to 62% of patients with spinal cord injuries (SCI), most commonly constipation, distention, abdominal pain, rectal bleeding, hemorrhoids, bowel accidents, and autonomic hyperreflexia. The acute abdomen, with a mortality of 9.5%, does not present with rigidity or absent bowel sounds but rather with dull/poorly-localized pain, vomiting, or restlessness, with tenderness, fever, and leukocytosis in up to 50% of patients. Fecal impaction may present with anorexia and nausea. Methods used for bowel care include laxatives, anal massage, manual evacuation, and enemas. Randomized, double-blind studies demonstrated the effectiveness of neostigmine, which increases cholinergic tone, combined with glycopyrrolate, an anticholinergic agent with minimal activity in the colon that reduces extracolonic side-effects. Improved bowel function occurs with anterior sacral root stimulators which may be combined with an S2 to S4 posterior sacral rhizotomy which interrupts the reflex arc by cutting the posterior roots carrying the spasticity-causing sensory nerves. For severe constipation, a colostomy reduces time for bowel care, providing a clean environment so decubitus ulcers may heal. Gallstones occur in 17% to 31% of patients, and acalculous cholecystitis in 3.7% of patients with acute SCI. A high index of suspicion is needed to properly diagnose bowel problems in SCI.

Infliximab and the TNF-alpha system.

Infliximab, a chimeric monoclonal antibody against TNF-alpha, is efficacious in Crohn's disease (CD) and rheumatoid arthritis (RA). Its main mechanism of action is thought to be the induction of apoptosis. The present study evaluates in detail the effects of infliximab on the TNF-alpha system using peripheral blood monocytes and T cells as well as lamina propria lymphocytes from normal individuals and patients with CD, ulcerative colitis, and RA. Lymphocytes were studied in the resting state in the absence of strong stimuli that may obscure subtle findings. Infliximab did not change the numbers of viable cells. Rather, it caused monocytes to increase their release of soluble TNFR2, which serves to neutralize TNF-alpha, potentiating the action of infliximab. It reduced TNFR2 expression, thereby decreasing TNF-alpha responsiveness. These changes were due to upregulated production of TNFR2 rather than increased shedding. Infliximab did not cause rebound production of TNF-alpha transcripts that would counteract its effects. It specifically enhanced production of IL-10 but not proinflammatory cytokines secreted by leukocytes, thereby promoting an anti-inflammatory microenvironment. In addition, infliximab caused a rise in c-Jun amino-terminal kinase phosphorylation by monocytes. Thus infliximab manipulates the TNF-alpha system to promote its anti-TNF-alpha effects.