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1/179. Use of transdermal amitriptyline gel in a patient with chronic pain and depression.

    A man with severe inflammatory bowel disease suffered from chronic abdominal pain and depression. A transdermal amitriptyline gel preparation was compounded since he was unable to take drugs orally serum concentrations of amitriptyline and its active metabolite nortriptyline were measured over 24 hours. Symptoms of depression were monitored before starting transdermal therapy and at the end of 6 weeks. Pain symptoms and amitriptyline adverse drug events were monitored daily Steady-state serum concentrations of drug and metabolite were within the therapeutic range over 24 hours. The patient reported that his mood was improved but his abdominal pain remained unchanged. Transdermal amitriptyline gel was well tolerated and is an alternative delivery system in patients unable to take drugs orally. ( info)

2/179. brain-gut axis and mucosal immunity: a perspective on mucosal psychoneuroimmunology.

    The role of the brain-gut axis has traditionally been investigated in relation to intestinal motility, secretion, and vascularity. More recently, the concept of brain-gut dialogue has extended to the relationship between the nervous system and mucosal immune function. There is compelling evidence for a reciprocal or bi-directional communication between the immune system and the neuroendocrine system. This is mediated, in part, by shared ligands (chemical messengers) and receptors that are common to the immune and nervous systems. Although the concept of psychoneuroimmunology and neuroimmune cross-talk has been studied primarily in the context of the systemic immune system, it is likely to have special significance in the gut. The mucosal immune system is anatomically, functionally, and operationally distinct from the systemic immune system and is subject to independent regulatory signals. Furthermore, the intestinal mucosal immune system operates in a local milieu that depends on a dense innervation for its integrity, with juxtaposition of neuroendocrine cells and mucosal immune cells. An overview of evidence for the biologic plausibility of a brain-gut-immune axis is presented and its potential relevance to mucosal inflammatory disorders is discussed. ( info)

3/179. Stress and mind-body impact on the course of inflammatory bowel diseases.

    At present, the medical management of inflammatory bowel diseases (IBD) including Crohn's disease and ulcerative colitis, are focused on topical, locally active antiinflammatories and systemic immunosuppressives, which are thought to exert their targeted effects in the gastrointestinal mucosa. There is a paucity of controlled trials assessing the impact of mind, central nervous system (CNS), and neuromodulation on the overly active immune response in the intestinal mucosa. patients and their physicians have long been aware of a strong association between attitude, stress, and flares of their IBD. Although reports to date remain mostly anecdotal, the degree to which mind-body influences and stress impact levels of local inflammation deserves closer attention with the aim of identifying contributing mechanisms, which may highlight new therapeutic interventions, as well as assist in identifying particular subsets of patients that may respond to novel forms of adjunctive treatments for IBD, including hypnosis, meditation, neuropeptide receptor modulation, and cortisol-releasing factor (CRF) modulation. ( info)

4/179. malpractice and avascular necrosis: legal outcomes.

    Every physician, but particularly specialists, have reason to be concerned about medical legal issues. Avascular necrosis has been established as a possible serious complication of steroid treatment in inflammatory bowel disease. Two specific Canadian cases illustrating the sequence of medical history, time, expert testimony and legal outcomes are presented. Awards plus costs in the order of $1 million or more were the result of these legal proceedings. The courts stated the major factors in finding liability against doctors were the failure to show the patient had been fully informed of treatment options. There was considerable weight given to expert testimony and the patient recollection of events to support their contentions. Adequate contemporaneous record keeping was absent to contradict evidence of the patients. The judges in both illustrative examples leaned heavily on Supreme Court of canada guidelines whereby the patient must be informed at all stages of the medical process. ( info)

5/179. Endovascular thrombolysis for symptomatic cerebral venous thrombosis.

    OBJECT: The authors sought to treat potentially catastrophic intracranial dural and deep cerebral venous thrombosis by using a multimodality endovascular approach. methods: Six patients aged 14 to 75 years presented with progressive symptoms of thrombotic intracranial venous occlusion. Five presented with neurological deficits, and one patient had a progressive and intractable headache. All six had known risk factors for venous thrombosis: inflammatory bowel disease (two patients), nephrotic syndrome (one), cancer (one), use of oral contraceptive pills (one), and puerperium (one). Four had combined dural and deep venous thrombosis, whereas clot formation was limited to the dural venous sinuses in two patients. All patients underwent diagnostic cerebral arteriograms followed by transvenous catheterization and selective sinus and deep venous microcatheterization. Urokinase was delivered at the proximal aspect of the thrombus in dosages of 200,000 to 1,000,000 IU. In two patients with thrombus refractory to pharmacological thrombolytic treatment, mechanical wire microsnare maceration of the thrombus resulted in sinus patency. Radiological studies obtained 24 hours after thrombolysis reconfirmed sinus/vein patency in all patients. All patients' symptoms and neurological deficits improved, and no procedural complications ensued. Follow-up periods ranged from 12 to 35 months, and all six patients remain free of any symptomatic venous reocclusion. Factors including patients' age, preexisting medical conditions, and duration of symptoms had no statistical bearing on the outcome. CONCLUSIONS: patients with both dural and deep cerebral venous thrombosis often have a variable clinical course and an unpredictable neurological outcome. With recent improvements in interventional techniques, endovascular therapy is warranted in symptomatic patients early in the disease course, prior to morbid and potentially fatal neurological deterioration. ( info)

6/179. Chronic pancreatitis and inflammatory bowel disease: true or coincidental association?

    OBJECTIVE: Several cases of pancreatitis have been described during the course of Crohn's disease (CD) or ulcerative colitis (UC), but many of them were related to either biliary lithiasis or drug intake. We tried to evaluate the clinical and morphological features of so-called idiopathic pancreatitis associated with inflammatory bowel disease and to define their pathological characteristics. methods: Chronic idiopathic pancreatitis was diagnosed on the basis of abnormal pancreatograms suggestive of chronic pancreatitis associated with or without impaired exocrine pancreatic function, or pathological examination in patients undergoing pancreatic resection. We found 6 patients presenting with features of chronic idiopathic pancreatitis and UC and 2 patients with CD seen between 1981 and 1996 in three hospital centers of the south of france. A review of the literature has identified 6 cases of pancreatitis associated with UC and 14 cases of pancreatitis associated with CD based on the above criteria. RESULTS: hyperamylasemia was not a sensitive test since it was present in 44% and 64% of patients with UC or CD. In UC, pancreatitis was a prior manifestation in 58% of patients. In contrast, the pancreatitis appeared after the onset of CD in 56% of the cases. In patients with UC, pancreatitis were associated with severe disease revealed by pancolitis (42%) and subsequent surgery. bile duct involvement was more frequent in patients with UC than with CD (58% vs 12%) mostly in the absence of sclerosing cholangitis (16% vs 6%). weight loss and pancreatic duct stenosis were also more frequent in UC than in CD (41% vs 12% and 50% vs 23%, respectively). Pathological specimens were analyzed in 5 patients and demonstrated the presence of inter- and intralobular fibrosis with marked acinar regression in 3 and the presence of granulomas in 2 patients, both with CD. CONCLUSIONS: pancreatitis is a rare extraintestinal manifestation of inflammatory bowel disease. Chronic pancreatitis associated with UC differs from that observed in CD by the presence of more frequent bile duct involvement, weight loss, and pancreatic duct stenosis, possibly giving a pseudotumor pattern. ( info)

7/179. Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil.

    In humans, 80-90% of an administered dose of 5-fluorouracil (5-FU) is degraded by dihydropyrimidine dehydrogenase (DPD; EC 1.3.1.2), the initial rate-limiting enzyme in pyrimidine catabolism. Cancer patients with decreased DPD activity are at increased risk for severe toxicity including diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity, and, in some cases, death. We now report the first known cancer patient who developed life-threatening complications after treatment with topical 5-FU and was shown subsequently to have profound DPD deficiency. RT-PCR and genomic PCR methodologies were used to identify a G to A mutation in the GT 5' splicing recognition sequence of intron 14, resulting in a 165-bp deletion (corresponding to exon 14) in this patient's DPD mRNA. immunoprecipitation and Western blot analysis were then used to demonstrate that the aberrant DPD mRNA is translated into a nonfunctional DPD protein that is ubiquitinated. We conclude that the presence of this metabolic defect combined with topical 5-FU (a drug demonstrating a narrow therapeutic index) results in the unusual presentation of life-threatening toxicity after treatment with a topical drug. These data further suggest that degradation by the ubiquitin-proteosome-mediated system plays a role in the elimination of the DPD protein. ( info)

8/179. diagnosis and management of inflammatory bowel disease.

    The chronic, unpredictability of inflammatory bowel disease makes it difficult for patients to cope. In fact several studies quoted by Cox (1995) found that the Majority of IBD patients, even the one's who considered themselves "well," experienced some impairment in quality of life. Early detection of IBD is essential in developing patient confidence and providing motivation for cooperation in treatment. Irvine (1997) conducted a study dealing with the quality of life issues with IBD and concluded that despite impairments, most patients with IBD overcame the obstacles imposed by their illness and managed to remain productive members of society. Similar management (with anti-inflammatory drugs) makes differentiating between Crohn's disease and ulcerative colitis during the early stages of the disease, unnecessary. Situations that require differentiation include: right sided pain or tenderness, steatorrhea, nutritional deficiencies, or a palpable mass (Macrae & Bhathal, 1997). Although IBD continues to be of unknown etiology, recent advances and further study in the areas of the immune system, genetics and environmental influences may provide helpful treatment options in the future. For now, the clinician/patient goal must be to maintain adequate nutrition, promote healing, treat complications, and maintain an optimal lifestyle. ( info)

9/179. Two cases of inflammatory bowel disease with multiple myeloma.

    A significant increase has been reported in reticuloendothelial neoplasms in patients with inflammatory bowel diseases. We present two rare cases of multiple myeloma in patients with inflammatory bowel diseases. One was in a 58-year-old woman with ulcerative colitis, and the other was in a 59-year old woman with Crohn's disease. In both patients, multiple myeloma occurred during long-term observation of inflammatory bowel disease and during the inactive stage of intestinal inflammation. The multiple myeloma appeared to have resulted from monoclonal gammopathy of undertermined significance in both patients, and was diagnosed by characteristic serum and bone marrow findings. Our findings suggested that multiple myeloma should be particularly considered in women of middle or advanced age with ulcerative colitis or Crohn's colitis and serum monoclonal gammopathy. ( info)

10/179. Microscopic colitis syndrome: lymphocytic colitis and collagenous colitis.

    Microscopic colitis is a syndrome consisting of chronic watery diarrhea, a normal or near-normal gross appearance of the colonic lining, and a specific histological picture described as either lymphocytic colitis or collagenous colitis. Since its initial descriptions a quarter of a century ago, microscopic colitis has become a frequent diagnosis in patients with chronic diarrhea. Understanding of the cause and pathogenesis of microscopic colitis remain incomplete, but potentially important clues have been discovered that shed light on predisposing factors. In particular, specific HLA-DQ genotypes may be permissive for the development of microscopic colitis, and suggest a linkage to the pathogenesis of celiac sprue. Although the differential diagnosis of chronic watery diarrhea is broad, the diagnosis of microscopic colitis is straightforward, involving endoscopic inspection of the colonic mucosa and proper pathologic interpretation of biopsy specimens. As the limitations of drugs ordinarily used for other forms of inflammatory bowel disease are being recognized, new approaches, such as the use of bismuth subsalicylate, are being evaluated. The prognosis of patients with microscopic colitis syndrome remains good, and symptomatic improvement can be expected in most patients. ( info)
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