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Biomedical subjects

W Petritsch

Publications and source records attributed to W Petritsch.

At least 19 recordsLinked to original sources

6-Thioguanine treatment in inflammatory bowel disease: a critical appraisal by a European 6-TG working party.

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity.

Antimetabolites, Antineoplastic↗

[Aminosalicylates and steroids in the treatment ot chronic inflammatory bowel diseases--consensus paper of the Working Group for Chronic Inflammatory Bowel Diseases of the OGGH].

5-aminosalicylates (5-ASA) and steroids constitute a cornerstone of medical therapy in patients with inflammatory bowel diseases (IBD). Whereas the efficacy of 5-ASA in Crohn's disease (CD) is equivocal, ulcerative colitis (UC) is the main indication for this drug. In UC, 5-ASA is effective in the treatment of mild to moderate acute disease and in maintenance of remission. Furthermore, 5-ASA topical therapy is an important treatment option in patients with mild to moderate proctitis and/or left-sided UC and shows additive efficacy to oral therapy. From retrospective data a chemo-preventative activity of long-term 5-ASA therapy in UC is delineated. Steroids are treatment of first choice for moderate to severe cases of CD and UC. Budesonide, a modified steroid with less side effects, plays a major role in the treatment of ileocolonic CD +/- involvement of the right colon and is used as treatment of choice in mild-to-moderate cases. In case of acute, severe disease conventional steroids are superior compared to budesonide and therefore budesonide should only be used after considerable improvement of disease activity. The necessity to apply steroids in a given patient represents a negative prognostic indicator for the course of disease and should incite the early introduction of immunosuppressive therapy in this case. Steroids are only effective as short term therapy of IBD and are to be avoided for maintenance treatment. In all cases of steroid therapy an osteoporosis prophylaxis with calcium and vitamin D is recommended. Topical steroid treatment is less effective in left-sided UC compared to 5-ASA.

Aminosalicylic Acids↗

[Endoscopy in IBD. A Consensus Report of the IBD Working of the Austrian Association of Gastroenterology and Hepatology].

Ileocolonoscopy including biopsies is the first line investigation in suspected inflammatory bowel disease (IBD). In up to 90 % of the cases ulcerative colitis and Crohn's disease are differentiated on endoscopic presentation. Standardised reporting of endoscopic results increases the validity and comparability of IBD findings. When there is a firm diagnosis of IBD, colonoscopy should only be performed for specific questions. An upper gastrointestinal endoscopy is only indicated in patients with upper gastrointestinal symptoms. Push and capsule endoscopy should also be limited to specific questions and situations. IBD with extended colitis is associated with an increased risk for colorectal cancer. Endoscopic surveillance with accurate biopsy sampling is a valuable tool for the prevention of colorectal cancer.

Endoscopy, Gastrointestinal↗

Mycophenolate mofetil for Crohn's disease: short-term efficacy and long-term outcome.

AIM: To assess the long-term efficacy of the antimetabolite agent mycophenolate mofetil in patients with Crohn's disease. METHODS: Twenty patients with complicated Crohn's disease were treated with mycophenolate mofetil, 1 g b.d., for up to 7 years. Twelve patients were intolerant to azathioprine, seven were resistant to azathioprine and one had a history of mesalazine-induced pancreatitis. The response to mycophenolate mofetil was determined by calculation of the Harvey-Bradshaw index, the ability to taper steroids and the grading of fistula activity. RESULTS: After 6 months, 11 of the 20 patients had responded. Seven of the 11 responders relapsed after a median of 18 months, three have an ongoing response at month 17, 19 and 82, and one discontinued mycophenolate mofetil owing to toxicity. After initial treatment failure, mycophenolate mofetil was continued in 12 of 17 patients for a further 2-41 months without inducing a stable remission. Mycophenolate mofetil was of benefit in nine of the 12 patients intolerant to azathioprine and in two of the seven patients resistant to azathioprine. Perianal fistulas improved in seven of eight patients; five of the seven subsequently deteriorated, but only one due to reactivated perianal disease. CONCLUSIONS: Mycophenolate mofetil was initially effective in a sizeable fraction of patients with complicated Crohn's disease, but relapse within 18 months was common. Nevertheless, mycophenolate mofetil could be a useful alternative in patients intolerant to azathioprine.

Adolescent↗

[Immunosuppressive therapy for inflammatory bowel disease: consensus by the Austrian working group on IBD].

Azathioprine (AZA) or 6-mercaptopurine (6-MP) are the immunosuppressive drugs of choice in the treatment of inflammatory bowel disorders (IBD). Optimal dosage for AZA is around 2.5 mg/kg body weight and induction of remission by these drugs may take 6 - 7 months. Intramuscularly applied Methotrexate (MTX) is the second choice, while its efficacy starts earlier than that of AZA; studies assessing oral low-dose MTX treatment are lacking. Cyclosporin is the standard treatment in case of steroid-refractory severe ulcerative colitis. This drug may also be used in patients with severe extraintestinal manifestations of IBD. Regarding other immunosuppressive drugs such as mycophenolic acid or 6-thioguanine respective controlled clinical study data are not available. The risk of malignancy using immunosuppressive drugs such as AZA is low and furthermore, especially AZA and 6-MP can be used rather safely during pregnancy.

Administration, Oral↗

Effect of oral tacrolimus (FK 506) on steroid-refractory moderate/severe ulcerative colitis.

BACKGROUND: Steroid refractory ulcerative colitis is most commonly treated with intravenous ciclosporin to avoid colectomy. In search for an alternative drug that can be administered orally we investigated oral tacrolimus (FK 506) for this indication. METHODS: Nine patients with active, moderate/severe steroid refractory UC were treated with oral tacrolimus with a daily dose of 0.15 mg/kg body weight. After patients had responded azathioprine was added for long-term immunosuppression. RESULTS: All patients responded within 1-2 weeks. After 12 weeks of tacrolimus therapy six patients (67%) were in complete remission, two patients (22%) had mild to moderate disease activity, and one patient (11%) underwent colectomy. After a mean follow up of 21 months six of the nine patients (67%) had their colon in situ. Two patients developed severe side-effects, one thrombopenia with intestinal bleeding, and one bicytopenia. Mild side-effects were common. CONCLUSION: Oral tacrolimus may be an effective alternative to intravenous ciclosporin for the therapy of steroid-refractory ulcerative colitis. Patients receiving tacrolimus need to be watched carefully for side-effects.

Administration, Oral↗

Examination, prevention and treatment of osteoporosis in patients with inflammatory bowel disease: recommendations and reality.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of developing osteopenia and osteoporosis. Our aim was to evaluate the current practices of examination, prevention and treatment of osteoporosis in IBD patients in a routine clinical setting. METHODS: A total of 154 consecutive patients with IBD (63 female, 91 male; 36 ulcerative colitis, 115 Crohn's disease, 3 indeterminate colitis), referred to two gastroenterological units for scheduled follow-up examinations, were included. Patient charts were evaluated regarding bone densitometry already performed and any prophylactic or therapeutic interventions in cases of low bone mineral density. RESULTS: Bone mineral density (BMD) measurements had been performed only in 38 patients (25%). BMD was abnormally low in 27 of the examined patients (71%), 20 of whom had osteopenia and seven had osteoporosis. Among the subgroup of patients on long-term steroid therapy (77 patients), 30 had been referred to bone densitometry during the course of disease, and 21 of them were found to have low bone mineral density. Preventive measures were prescribed in 12 patients (9% of the whole study population). In the majority of the patients with low bone mineral density, calcium and vitamin D were used as treatment. CONCLUSIONS: Despite the high prevalence of osteopenia and osteoporosis in patients with IBD, only a minority of these patients were included in a structured program in accordance with modern guidelines for diagnosing and preventing this extraintestinal complication in a routine clinical setting.

Absorptiometry, Photon↗

Use of anti-tumour necrosis factor agents in inflammatory bowel disease. European guidelines for 2001-2003.

The introduction of novel anti-tumor necrosis factor (TNF) agents has not only led to impressive new therapeutic opportunities but also resulted in uncertainty regarding their optimal use and possible side effects. Guidelines are presented here for the use of anti-TNF agents in gastrointestinal disorders. Experts were chosen from different European countries by an algorithm to avoid bias. An expert consensus on guidelines was established using a two-stage procedure of systematic Medline and abstract search for evidence and a qualifying meeting to derive recommendations. Detailed guidelines were developed for the use and the future clinical development of anti-TNF agents in inflammatory bowel disease. Grading of available evidence and grading of recommendations were performed according to AHCPR guidelines. At present infliximab is the only registered agent for Crohn's disease. Infliximab should be always used at a dose of 5 mg/kg. The guidelines define the indications both in refractory and in fistulating disease for the readministration and before surgery. Guidelines for safety and for concomitant treatments are given. Prospects, potential clinical use, and future directions for the clinical development of other anti-TNF agents are detailed. Clinical use of anti-TNF agents will be influenced by a large number of clinical trials being concluded in 2001 and 2002. It is likely that anti-TNF therapies will become an important long-term therapy for a proportion of patients with Crohn's disease. Biological agents will be followed by smaller and more stable, orally available compounds. These guidelines will be succeeded by a formal public consensus in 2002/2003.

Crohn Disease↗

Gastric adenocarcinoma mimicking achalasia in a 15-year-old patient: a case report and review of the literature.

Although adenocarcinoma of the cardia is extremely rare in adolescent patients, the endoscopist should be alert to this disease in patients of any age with dysphagia, even if symptoms, and results of a barium study, upper endoscopy, and esophageal manometry are suggestive of primary achalasia, especially if family history is negative for achalasia. In addition, secondary achalasia should be suspected in patients who do not respond to therapy with botulinum toxin within 2 months. Because none of the mentioned tests can distinguish between primary achalasia and secondary forms due to carcinoma of the cardia, biopsy specimens should be obtained. It appears that, although there is a minimal risk for complications, a diagnostic procedure such as biopsy would be appropriate when the information obtained could be essential. In some cases EUS can be an additional diagnostic tool, because lesions of the submucosa and the surrounding area can be identified by EUS.

Adenocarcinoma↗

Prediction of response to iron sucrose in inflammatory bowel disease-associated anemia.

OBJECTIVE: Inflammatory bowel disease (IBD)-associated anemia responds to i.v. iron therapy. However, because of concurrent chronic inflammation, some patients do not respond adequately. Erythropoietin therapy has been shown to be effective in the latter cohort. Our goal was to find parameters that can predict the effectiveness of iron sucrose in IBD-associated anemia. METHODS: One hundred three patients with severe IBD-associated anemia (Hb < or = 10.5 g/dl) were treated prospectively for 4 wk with iron sucrose (total iron dose = 1.2 g) in an open label, multicenter trial. Treatment response was defined as an increase in Hb of > or =2.0 g/dl. A logistic regression analysis was performed with treatment response as the dependent variable and the following independent variables: serum erythropoietin, mean corpuscular Hb, transferrin, ferritin, soluble transferrin receptor (sTfR), C-reactive protein, interleukin 6 (IL-6), and disease activity. RESULTS: Sixty-seven of 103 patients (65%) responded to iron sucrose. From the variables under investigation, erythropoietin, sTfR, transferrin, and IL-6 were significantly associated with treatment response. The R2 values showed that erythropoietin (8.0%), sTfR (11.4%), and transferrin (10.4%), but not IL-6 (1.3%), contribute a relevant amount of information to the model. An estimated 80% probability of treatment response was found at erythropoietin levels of >166 U/L, sTfR levels of >75 nmol/L, or transferrin levels of >3.83 g/L. CONCLUSIONS: Serum erythropoietin, sTfR, and transferrin concentrations have the potential to predict the response to iron sucrose therapy in IBD-associated anemia. These parameters may help to identify individuals who benefit the most from additional erythropoietin treatment.

Anemia, Iron-Deficiency↗

Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI.

BACKGROUND & AIMS: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. METHODS: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. RESULTS: Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). CONCLUSIONS: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

Adult↗

[Consensus of the Chronic Inflammatory Bowl Disease Study Group of the Austrian Society of Gastroenterology and Hepatology on the topic of "diagnosis and therapy of chronic inflammatory bowel diseases in adolescence"].

Although up to 20% of patients with Crohn's disease have their first flare during childhood or adolescence, there are no or only a few randomized, controlled studies. However, big differences and uncertainty may be observed between the diagnosis and therapy of pediatricians and gastroenterologists specialized for adults. In addition, special problems result from the enormous somatic and psychological evolution during adolescence. The diagnosis is done as in adult patients by enteroclysm and ileocolonoscopy (including multiple biopsies) whereas a deep sedoanalgesia or anesthesia should be performed routinely. Corticosteroids are the gold standard for therapy of Crohn's disease in the adolescence (especially in cases with high inflammatory activity), but also enteral nutrition over 4-12 weeks--or a combination of both. A recent randomized controlled study demonstrates the positive effect of 6-mercaptopurine in newly diagnosed patients with Crohn's disease in the adolescence. 5-aminosalicylates or the probably more effective azathioprine/6-mercaptopurine could be used for prevention of recurrence in Crohn's disease. The therapy of ulcerative colitis is performed as in adults including the very effective local rectal applications. An accompanying psychosomatic therapy is recommended especially in young patients with disturbed separation from the parents and inadequate coping. The indication for surgery is similar to adults. However, a specific indication for earlier surgery is given, if severe malabsorption and delay of growth takes place in spite of adequate therapy, because this delay of growth could be only caught up before puberty. A conservative therapeutic regimen is recommended in young patients with perianal Crohn's disease.

Adolescent↗

Anti-cardiolipin antibodies in patients with inflammatory bowel disease.

Elevated levels of anti-cardiolipin antibodies are associated with an increased risk for venous and arterial thrombosis. In patients with inflammatory bowel disease thrombosis is a well known complication. We determined the prevalence of elevated anti-cardiolipin antibodies in 136 patients with inflammatory bowel disease compared with 136 healthy controls and analyzed thromboembolic complications in patients with increased anti-cardiolipin antibody levels. Anti-cardiolipin antibody titers were significantly elevated in patients with Crohn's disease (5.7 units/ml) and ulcerative colitis (5.3 units/ml) compared to the control group (2.5 units/ml). We found no correlation between disease activity and anti-cardiolipin antibody levels. Seven patients had deep venous thrombosis in their history, in three of them this was complicated by pulmonary embolism. In only two of the seven patients with deep venous thrombosis were anti-cardiolipin antibody levels increased. In conclusion, anti-cardiolipin antibody titers were significantly increased in patients with inflammatory bowel disease. Elevated anti-cardiolipin antibody levels appear to play no role in the pathogenesis of thromboembolic events in patients with inflammatory bowel disease.

Adult↗

Mycophenolate mofetil in patients with Crohn's disease.

OBJECTIVE: Intolerance to azathioprine is a rare but important problem in treating chronically active Crohn's disease. We performed this study to evaluate mycophenolate mofetil as an alternative immunosuppressive therapy for patients with Crohn's disease who did not tolerate azathioprine. METHODS: Four patients with highly active perianal Crohn's disease and two patients with chronically active, steroid-dependent Crohn's disease were included. All patients consumed 2 g/day of mycophenolate mofetil for a median of 8 months (range, 6-12 months). Disease activity was measured by the Perianal Crohn's Disease Activity Index in patients with perianal disease and by the Crohn's Disease Activity Index in patients with chronically active Crohn's disease. RESULTS: Azathioprine-induced side effects disappeared after the drug was discontinued. All patients improved during treatment with mycophenolate mofetil, as shown by a remarkable reduction in the respective clinical scores. Five patients showed no side effects during treatment with mycophenolate mofetil. After 4 months' treatment one patient developed diarrhea that was probably not due to mycophenolate mofetil. CONCLUSION: Mycophenolate mofetil could be an alternative therapy to azathioprine in patients with Crohn's disease.

Adult↗

Intraluminal capsaicin does not affect fluid and electrolyte absorption in the human jejunum but does cause pain.

BACKGROUND: Stimulation of sensory nerves with capsaicin regulates ion transport in the small intestine in animal experiments. AIM: To investigate whether sensory nerves that are stimulated by capsaicin administration influence fluid and electrolyte absorption in the human jejunum in vivo. METHOD: Intestinal perfusion studies were performed in 12 healthy subjects using a four lumen tube with a proximal occlusion balloon and a plasma-like electrolyte solution. After an initial control period, 5 (n = 3), 10 (n = 8), or 50 (n = 1) micrograms/ml capsaicin was added to the perfusate, and this was followed by a final control period. Rates of absorption of water, sodium, potassium, chloride, and bicarbonate were determined in a 30 cm segment of jejunum using a non-absorbable volume marker. RESULTS: At all three concentrations of capsaicin there were no significant changes in water and electrolyte absorption as compared with control periods. Two subjects who received 10 micrograms/ml and the subject receiving 50 micrograms/ml experienced crampy abdominal pain. CONCLUSION: The results do not support the hypothesis that capsaicin sensitive afferent nerves are involved in the physiological regulation of net absorption or secretion across the human jejunal mucosa. Chemical stimulation of these nerves, however, gives rise to abdominal pain.

Adult↗