Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As our understanding of integrins as multifunctional adhesion and signaling molecules has grown, so has their recognition as potential therapeutic targets in human diseases. Leukocyte integrins are of particular interest in this regard, as they are key molecules in immune-mediated and inflammatory processes and are thus critically involved in diverse clinical disorders, ranging from asthma to atherosclerosis. Antagonists that interfere with integrin-dependent leukocyte trafficking and/or post-trafficking events have shown efficacy in multiple preclinical models, but these have not always predicted success in subsequent clinical trials (e.g., ischemia-reperfusion disorders and transplantation). However, recent successes of integrin antagonists in psoriasis, inflammatory bowel disease, and multiple sclerosis demonstrate the tremendous potential of antiadhesion therapy directed at leukocyte integrins. This article will review the role of the leukocyte integrins in the inflammatory process, approaches to targeting leukocyte integrins and their ligands, and the results of completed clinical trials.
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PMID:Targeting leukocyte integrins in human diseases. 1554 73

Mesenteric venous thrombosis (MVT) is a rare but potentially catastrophic clinical complication, which may lead to ischemia or infarction of the intestine and/or the emergence of portal hypertension. An association between inflammatory bowel disease (IBD) and MVT has previously been described, but clinical factors that may contribute to this complication in the setting of IBD are not well characterized. Diagnosis of MVT in IBD is difficult, as patients frequently present with nonspecific abdominal discomfort, which may delay diagnosis and initiation of treatment. We report 6 of 545 IBD patients at our center (1.1%) that developed MVT, and describe presentation, diagnostic approaches, treatment options, underlying contributing factors, and outcome. The diagnosis was determined with abdominal computed tomography (CT) in 5 of 6 cases. Clinical factors, which were thought to contribute to MVT, included underlying hypercoagulability, low-flow state, uncontrolled inflammation, perioperative time period, and prior surgical manipulation of the portal vein following orthotopic liver transplantation. There were no deaths as a result of MVT, although 1 patient developed severe portal hypertension and another experienced intestinal infarction requiring extensive resection. We conclude that MVT is an important clinical consideration in IBD patients, specifically during the perioperative setting, and diagnosis is facilitated with the use of CT scan.
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PMID:Mesenteric venous thrombosis in inflammatory bowel disease. 1559 6

Clinically significant anastomotic strictures usually only occur with very low colorectal anastomoses below the level of the peritoneal reflection. The reported rate averages 8 percent and has been attributed to tissue ischemia, localized sepsis, anastomotic leak, proximal fecal diversion, radiation injury, inflammatory bowel disease, and recurrent rectal cancer. Most patients will have symptoms of obstipation, frequent small bowel movements, and bloating. Symptomatic strictures are often approached by dilation (balloon or Hegar) or less often repeat resection. Many of these patients have anastomoses that are too low to consider repeat resection. Strictureplasty with linear stapling devices, stricture resection by use of the circular stapling device, and repeat dilations have all been described. Steroid injections into the stricture have been described in strictured esophagogastric anastomoses but have not been commonly used for strictured coloproctostomies. We describe three cases of coloanal stricture following resections that were complicated by postoperative pelvic abcesses, anastomatic leaks, and pelvic fibrosis. Two cases had undergone low coloanal anastomosis that was protected by a loop ileostomy and developed as significant stricture in the early postoperative period. The third case was managed without a protective loop ileostomy. These were initially managed by repeated dilation of the anastomosis. Each episode was followed by rapid recurrence of the stricture. All patients underwent subsequent dilation with injection of 40 mg of triamcinolone acetate (divided dose in four quadrants) into the stricture and subsequent complete resolution of the stricture. Those patients with loop ileostomies had them taken down and all have been followed for up to 12 months without clinical or endoscopic evidence of recurrent stricture.
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PMID:The strictured anastomosis: successful treatment by corticosteroid injections--report of three cases and review of the literature. 1574 75

Schering-Plough's interleukin (IL)-10 (ilodecakin) is under investigation for the potential treatment of autoimmune diseases, solid tumors, ulcerative colitis, Crohn's disease and organ transplantation. In June 1996, ilodecakin entered phase II trials for Crohn's disease, ulcerative colitis and rheumatoid arthritis and, as of June 1999 was reported to be in phase III trials for Crohn's disease and rheumatoid arthritis. It has also demonstrated promising effects in the treatment of inflammatory bowel disease. In January 1997, phase I trials began in HIV-infected patients. Initial results from a pilot study, carried out by the National Institute of Allergy and Infectious Disease Control, indicated that a single dose of IL-10 decreases the blood viral load. The results, however, were transient. Early clinical studies are ongoing in acute lung injury, ischemia-reperfusion injury, multiple sclerosis and psoriasis. In February 1999, Morgan Stanley Dean Witter predicted sales of US $50 million in 2000 rising to US $325 million in 2005.
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PMID:Ilodecakin. Schering-Plough Corp. 1611 14

Comprehensive bowel examination results from the combined use of T2-weighted single-shot and breath hold T1-weighted gradient echo, minus/plus fat suppression, and gadolinium-enhanced 3D gradient echo (3D VIBE, T1 FAME, 3D THRIVE). Gadolinium-enhanced imaging should be performed dynamically, but the venous 60- to 90-second delayed phase images with fat suppression are generally the most valuable. Removal of fat signal for detection of enhancing normal and abnormal structures is critical. Newly available True-FISP (FIESTA, BFFE) sequences obtained in the 2D form can be very helpful in delineation of bowel wall pathology and overall bowel anatomy, particularly when combined with a water-based intraluminal distending agent. Advantages include rapid acquisition, high signal-to-noise, and motion insensitivity. Generalized protocol for comprehensive evaluation of the entire abdomen and pelvis can be used for the following bowel indications: type and severity of inflammatory bowel disease (IBD); identifying enteric abscesses and fistulae; preoperative staging of malignant neoplasms, including rectal carcinoma; differentiating postoperative and radiation therapy changes from recurrent carcinoma; follow-up evaluation of metastases response to localized ablative or systemic chemotherapy. For improved visualization of bowel wall in dedicated examinations, bowel distension should be achieved using either orally or rectally delivered contrast agents to produce either bright or dark lumen. We have found 2D True-FISP without fat suppression superior to 3D True-FISP and to single-shot echo-train sequences to provide a T2-weighted image of bowel morphology. Strengths include: performed without fat suppression results in the very dark bowel wall being sandwiched between intermediate high signal fat adjacent to bowel serosa, and very high lumen signal from water-distending agent; 2D True-FISP provides motion insensitivity that is lost if 3D is used; True-FISP produces better edge sharpness than single-shot echo-train, higher contrast, and resists flow void artifacts commonly seen with single-shot echo-train imaging combined with a water distending agent. Drawbacks of this technique include: artifacts related to extreme sensitivity to field inhomogeneity, including air-soft tissue interfaces at the patient skin surface, and from retained bowel gas; retained bowel gas is dark against dark bowel wall, impairing bowel wall assessment; and True-FISP does not provide sensitivity for edema, which is superior on single-shot echo-train imaging. Small/large bowel indications for MRI include: inflammatory bowel disease, infectious disease including abscess evaluation or for appendicitis, inflammatory conditions including ischemia, and partial obstruction, malnutrition, and neoplasm search.
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PMID:Magnetic resonance imaging of the gastrointestinal tract. 1631 98

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a relatively recently known and not very often diagnosed form of ischemic bowel disease of low incidence und unknown etiology. We present the case of a patient who after presentation of inconclusive signs of epigastric pain and rectal bleeding suddenly developed right abdominal pain with local peritonism. Suspecting intestinal ischemia or perforated appendicitis we first performed laparoscopy, which showed an inflammable tumor of cecum, ascending colon and appendix with massive adhesions to the abdominal wall. We performed an open right hemicolectomy with primary anastomosis. The patient developed a deep vein thrombosis of the vena tibialis post. and vena saphena parva. After 12 months our patient is free of complaints and recurrence. Investigations carried out showed no evidence of hypercoagulopathy. The presentation of MIVOD can range from chronic inflammatory bowel disease with recurrent abdominal pain in combination with nausea, emesis and bloody diarrhea to acute abdomen. Therefore diagnostic misinterpretation and mistherapy as well as underdiagnosis is common. Histologic investigation shows a variable inflammatory infiltration of multiple veins of the intestinal wall and the mesentery as well as thrombotic vessel occlusion in different stages without involvement of the arteries. All forms of hypercoagulopathy, parasitic disease, sepsis and malignancy have to be excluded. Therapeutic success can only be achieved with surgical resection of the affected bowel, whereon in general no recurrence will occur.
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PMID:[Mesenteric inflammatory veno-occlusive disease (MIVOD)--a rare cause of intestinal ischemia]. 1639 91

The evaluation of patients with colitis of recent onset is a relatively common clinical challenge. The main considerations are infectious colitides, idiopathic IBD, ie, ulcerative and Crohn's colitis, and colonic ischemia. An initial risk assessment on the basis of such factors as concurrent symptoms in contacts, travel history, medications, and human immunodeficiency virus risk factors should be followed by a thorough clinical history, physical examination, stool studies, blood tests, and, in selected cases, endoscopic examination and serologic tests. Biopsies can be decisive in distinguishing among the different types of acute colitis and might help identify specific etiologies. The diagnostic yield of biopsies is maximized by appropriate sampling of the colonic mucosa and by sharing the clinical and endoscopic findings with the pathologist, eg, via a copy of the endoscopy report.
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PMID:Diagnosis of colitis: making the initial diagnosis. 1791 88

The short bowel syndrome (SBS) can result from a variety of conditions, including postoperative complications and malignancy. Continence-preserving operations are generally performed for either ulcerative colitis (UC) or familial polyposis (FAP). These procedures can be associated with high morbidity and the potential for future malignancy. Our aim was to determine the causes and consequences of SBS in patients undergoing these procedures. Twenty-four patients (12 men and 12 women) 18 to 64 years of age were identified with SBS after continence-preserving procedures. Eighteen had pelvic procedures, and six had continent ileostomies. All SBS patients had a proximal ostomy. Remnant length measured <60 cm in five patients, 60-120 cm in ten patients, and >120 cm in nine patients. Overall 13 patients required long-term PN. Four FAP patients with desmoid tumors died. One patient with UC underwent intestinal transplant and expired. Follow-up ranges from 6 to 192 months. Overall 14 patients had UC, nine had FAP, and one had functional disease. Eight patients with an initial diagnosis of UC had subsequent Crohn's disease necessitating further resection and pouch excision. Eight patients (five with UC, two FAP, and one with functional disease) had postoperative complications, including obstruction or mesenteric ischemia requiring resections. One UC patient developed adenocarcinoma in a continent ileostomy. Seven of the nine FAP patients required resection for desmoid tumors. Six of these underwent resection alone. Three died at 10, 11, and 13 months after SBS from liver failure and sepsis while awaiting transplant. One patient has recurrent desmoid at 30 months, another is alive and well at 48 months, and the other patient, who was not a transplant candidate, died from an unrelated cardiac operation at 23 months. A single patient underwent resection with simultaneous multivisceral transplantation. SBS can develop after continence-preserving procedures. This occurs with inflammatory bowel disease when unsuspected Crohn's disease is present or complications occur. SBS related to desmoid tumors has a poor prognosis in patients undergoing resection alone. A more aggressive approach to intestinal transplantation in these patients may be warranted.
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PMID:Short bowel syndrome after continence-preserving procedures. 1796 30

Isolated ulcers of the large intestine are not associated with an underlying colitis and may be an incidental finding on screening colonoscopy or present with abdominal pain, hematochezia, chronic gastrointestinal bleeding, and rarely, perforation. A common cause of isolated colonic ulcers is the use of nonsteroidal anti-inflammatory drugs (NSAIDs), with ulcers in the cecum and right colon. Isolated rectal ulcers are caused by ischemia, solitary rectal ulcer syndrome (SRUS), radiation, or fecal impaction. Stercoral ulceration and nonspecific ulcers of the colon are rare but can cause colonic perforation. Infectious causes include tuberculosis and amebiasis. Histology is important to rule out malignancy but is not helpful for diagnosis except in SRUS and certain infections. The approach to isolated colonic ulceration includes biopsy of the ulcer and surrounding tissue, cessation of any NSAIDs, management of constipation, and recognition of the patient with SRUS. Inflammatory bowel disease should be ruled out in appropriate patients.
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PMID:Isolated colonic ulcers: diagnosis and management. 1799 45

Recent advances in the ability to genetically interrogate microbial communities within the intestinal tract of humans have revealed many striking findings. That there may be as many as 300 unculturable and unclassified microbes within the human intestinal tract opens the possibility that yet-unidentified microbes may play a role in various human diseases [( 1) ]. Technologically, the regional and spatial aspects of intestinal microbial communities can now be better appreciated by emerging genetic and in vivo imaging systems using a bioinformatics approach [( 2) ]. Finally, in situ PCR of tissues and blood now allows the detection of microbes at concentrations that would otherwise remain undetected by culture alone [( 3) ]. In the aggregate, these studies have empowered clinicians to readdress the issue of how our microbial partners are affected by extreme states of physiologic stress and antibiotic use through the course of critical illness. The role of microbes in systemic inflammatory states, such as systemic inflammatory response syndrome, as well as in primary intestinal mucosal diseases, such as necrotizing enterocolitis, inflammatory bowel disease, and ischemia-reperfusion injury, can now be more completely defined, and the microbial genes that mediate the immune activation during these disorders can be identified. The 2008 roadmap initiative at the National Institutes of Health to fully define the human microbiome is further testament to the power of this technology and the importance of understanding how intestinal microbes, their genes, and their gene products affect the course of human disease and inflammation.
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PMID:The re-emerging role of the intestinal microflora in critical illness and inflammation: why the gut hypothesis of sepsis syndrome will not go away. 1816 May 38


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