Showing papers by "Fergus Shanahan published in 1994"

Low-dose 6-mercaptopurine in inflammatory bowel disease is associated with minimal hematologic toxicity.

Abstract: A feared complication of therapy with 6-mercaptopurine (6-MP) is myelosuppression. To evaluate whether rigorous blood count monitoring is necessary, we prospectively followed the hematologic profiles of 57 patients with inflammatory bowel disease who were treated with low-dose 6-MP. Most patients (97%) were treated initially with a single dose of 50 mg/day and 79% never used more than 50 mg/day. Blood counts were obtained at weekly intervals over the first month, every two weeks for the second month, and monthly thereafter in the first year. Sixteen (28%) developed mild leukopenia (white blood count 101 fl) was seen in nine (16%). In conclusion, leukopenia was not uncommon in patients treated with low-dose 6-MP, but was not clinically significant. Leukopenia occurred no earlier than three months and as late as 42 months into therapy. Thrombocytopenia was uncommon, mild, and was not associated with apparent bleeding. Macrocytosis may occur in the absence of vitamin B12 and folate deficiencies. Patients can be spared from weekly blood count monitoring when using low-dose 6-mercaptopurine treatment.

Neurotransmitters and cytokines in CNS pathology.

Abstract: In summary, we have demonstrated an in vitro model for oligodendrocyte cell death that may be relevant to events in formation of lesions in MS. It involves cell contact to oligodendrocytes with activated, viable microglia (or inflammatory macrophages), surface TNF-alpha, surface adhesion molecules, and production of NO. Precise mechanisms of TNF-alpha and ICAM-1/LFA-1 participation and the nature of the susceptibility of the oligodendrocyte are currently being studied.

Current concepts of the pathogenesis of inflammatory bowel disease.

Abstract: Although the cause of inflammatory bowel disease is not known, the pathogenesis involves an immune-mediated tissue damage that is the result of an interaction among genetic predisposing factors, exogenous triggers and endogenous modifying influences. Multiple genes are involved and operate at the level of the immune response and at the target organ. Exogenous triggers include the enteric microflora which might stimulate the mucosal immune system in genetically predisposed individuals. Endogenous modifying factors such as the psychoneuroendocrine system have regulatory effects on the immune system and the inflammatory response, and may influence the course of the disease. While autoimmune phenomena do occur, particularly in ulcerative colitis, there is no evidence that they are directly responsible for the tissue damage. It appears more likely, particularly in Crohn’s disease, that tissue injury may occur as an indirect or “bystander” effect of mucosal T-cell hyperactivation, perhaps in response to a normal enteric microbial antigen. Most of the immunologic and histologic features of Crohn’s disease can be explained by the effects of T-cell derived and other cytokines on the epithelium, the local immune system, the microvasculature, and the recruitment of auxilliary effector cells such as neutrophils.

Immunosppressive Agents in Inflammatory Bowel Disease: Current Status and Future Prospects

Abstract: Inflammatory bowel disease involves an interaction between genetic susceptibility factors and environmental triggers, and the intestinal injury is mediated by the host immunoinflammatory response. Identification of the mechanisms and mediators that contribute to the tissue injury has provided a sound rationale for the therapeutic use of immunosuppressive and immunomodulatory agents. The efficacy of traditional immunosuppressive drugs, such as the purine analogues in both Crohn’s disease and ulcerative colitis, is well established. The major limitation of the use of these drugs is the delayed clinical response associated with their use. This has prompted an evaluation of other immunosuppressivcs, such as cyclosporine and related drugs, that have a more rapid onset of action. Convincing data indicate a distinct role for cyclosporine in certain patients with acute severe ulcerative colitis. However, despite early promising results with cyclosporine in Crohn’s disease, recent results have been less encouraging. There is also uncertainty about the exact clinical role of cyclosporine because of concerns regarding long term toxicity. At present, many investigators regard cyclosporine as an interim measure for acutely ill patients. The challenge that remains is the development of novel immunomodulatory strategies that are specific for the mucosal immune system and that are based on recent advances in our understanding of the pathogenesis of mucosal inflammation.

Irish Society of Gastroenterology: Proceedings of Poster Section of meeting held in Cork, June 3rd/4th 1994

Abstract: Over a period of 8 years, 24 patients were referred to this unit with post operative biliary strictures or fistulae~ There were 16 female and 8 male patients (age range 22-76 years). Clinical presentations included jaundice, fever and chills, biliary leak and bile peritonitis. The injury followed cholecystectomy in 20 cases and liver transplantation in 4 cases. Six patients had attempted repair prior to referral. Two patients had more than one previous repair. Diagnostic imaging ~tudies in this unit included percutaneous transhepatic cholangiography (16), ERCP (9) and HIDA scan (8). One patient with advanced septicemia and renal failure died before surgery. Two patients were treated by balloon dilatat ion. The other 21 patients had surgical co r r ec t i on of the s t r i c tu re or f i s tu la : Roux-en-Y hepaticojejunostomy (17), choledocho duodenostomy (1), end to end repair (1), liver resection (1), re-transplantation (1). There were no operative deaths. Post-operative complications included wound infection, septicemia and bile leak. One patient who had ba l loon d i la ta t ion had a good resul t for 12 months but subsequently had a surgical repair. The other patient who had balloon dilation has had a good result for up to 4 years. Of the 21 patients treated surgically, 1 patient had recurrent cholangitis and developed secondary biliary cirrhosis and died after 4 years. The remaining 20 patients have had a good result and remain free of symptoms from 3 months to 8 years after surgery. Modem therapeutic approaches to bile duct strictures and fistulae include nonoperative procedures, but the majority of patients require surgical repair. The risk of recurrence requires that long term follow up is essential.