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To regulate intestinal transit, increased fluid intake, along with fiber is recommended. Considering the usually large volumes of intestinal secretion, this advice is questionable. To demonstrate the effects of adding fluid to fiber, 11 volunteers ingested 15 g of wheat bran twice a day, randomly given without or with 600 mL of additional fluid. Stool weight and frequency were similarly increased in the two settings. Gastric emptying was delayed by bran only when bran was given without additional fluid. Orocecal transit showed no significant changes. Whole gut transit was slightly more accelerated with added fluid (20.6 vs. 13.5%). No test showed significant differences in direct comparison of bran and bran with additional fluid. We conclude that in healthy persons, such effects of wheat bran as acceleration of transit and increase in stool weight and frequency do not depend on an additional intake of fluid.

New concepts are developed in the therapy of diverticular disease. 5-aminosalicylates can be administered in patients with slight forms of diverticulitis. In moderate diverticulitis antibiotics should be applied alternatively or additionally. In cases of severe diverticulitis patients should be kept fasting with parenteral nutrition and intravenous broad spectrum antibiotics. Small abscesses can be treated conservatively while abscesses larger than 4 cm should be drained in a first step and than treated surgically. A free perforation is still an absolute indication for emergency operation. In recurring diverticulitis indication for resection of the affected segment of the bowel should be considered depending on the extent of former attacks.

Background and study aims Ileocolonoscopy including biopsies is the first-line investigation in the diagnosis, management, and monitoring of inflammatory bowel disease (IBD). However, data on its safety, feasibility, and tolerability, especially in patients with extensive or severe inflammation, are rare. The aim of this study was to assess prospectively the risks of ileocolonoscopy in relation to various disease patterns and to compare possible burdens of the procedure in the endoscopist's and the patient's perception. Patients and methods We prospectively analyzed a total of 558 consecutive patients, 482 with a confirmed diagnosis of IBD and 76 with suspected IBD. Data were recorded regarding the indication for ileocolonoscopy, sedation, procedure time, completion rate, feasibility of the procedure, patient tolerance, and procedure-related and postprocedure complications. Endoscopic data included the region involved, the nature of the involvement, activity of the disease, and number of biopsies. Results In 558 endoscopic procedures performed by 14 gastroenterologists no procedure-related deaths occurred. Major complications, defined as bleeding (n = 1) or perforation (n = 3), occurred in 4/558 patients (0.7 %). Minor complications, which included intense flatulence, tachycardia, allergic reaction to a sedation drug, and autonomic symptoms such as nausea, vomiting, and intense perspiration, occurred in 22/558 patients (3.9 %). There was no relationship between the complication rate and the activity of the disease. Mean procedure time was 21.0 minutes and the completion rate, defined by intubation of the terminal ileum, was 94.6 %. We documented a high tolerability independent of the severity of the disease. Conclusions Ileocolonoscopy is a safe and feasible procedure in patients with IBD and is well tolerated by patients when carried out by well-trained endoscopists.

Functional bowel disorders cause frequent doctor visits. The term comprises various disease entities. Most frequent are the irritable bowel syndrome, functional constipation and functional diarrhea. An exact history plays an outstanding role for the diagnosis of all these entities. History either confirms a positive diagnosis or initiates some complementary investigations. Redundant and dangerous technical procedures should be avoided in the diagnostic work up.

Current data show that probiotics are more effective in preventing the recrudescence of an inflammatory process than in suppressing active disease. This is reflected in the solid evidence for the effect of E. coli Nissle 1917 (Mutaflor) in the maintenance of remission of ulcerative colitis, and of VSL#3 in preventing the recurrence of pouchitis. These indications have since been incorporated in valid guidelines. Initial clinical studies have also provided promising results regarding the efficacy of VSL#3 in preventing pouchitis immediately following proctocolectomy.

In Crohn's disease therapeutic concepts are according to distinct conditions. Course of the disease, the individual disease pattern and the aim of treatment are of particular significance. Care of patients with Crohn's disease requires interdisciplinary cooperation between gastroenterologists and surgeons. Primary therapy in mild to moderate disease comprises aminosalicylates and budesonide. Treatment of refractory or severe cases are corticosteroids. Immunosuppressive therapy is indicated in all kinds of complicated disease. First line immunosuppressants are Azathioprine and 6-Mercaptopurine while Methotrexate, Infliximab, Mycophenolatmofetil and other compounds represent alternative or rescue medications. Maintenance of remission should not be done on a regular basis but rather regarding the individual patients' situation. Risks have to be carefully balanced with possible benefits. The most important aim of treatment is quality of life.

Within a few weeks a 78-year-old woman presented three times in hospital with dramatic blood loss in need of transfusion. At her admission to hospital she complained about general weakness and painless melena. Within the last few years the patient had been treated with aspirin and phenprocoumon for chronic atrial fibrillation and coronary heart disease.Laboratory findings revealed a very low hemoglobin of 6 g/dl when the patient presented at hospital. The esophagogastroduodenoscopy was normal. The first colonoscopy detected diverticula of the left colon and fresh blood in the whole colon. The definitive bleeding site could not be identified. A technetium-colloid scan revealed an increased blood loss in the right colon. A second colonoscopy performed at the same time confirmed a right sided bleeding and an active capillary bleeding in the coecum without any mucosal lesion was identified.As during the patient's first stay at hospital the site of lower gastrointestinal bleeding could not be determined, the patient was treated by transfusion and oral anticoagulation was stopped. The bleeding stopped spontaneously within a few days. At the third rebleeding episode examinations located the bleeding in the right colon, and a right hemicolectomy was performed. After the operation a piece of chicken bone was detected in the wall of the coecum, which had led to a chronic mucosal bleeding after penetration of the colonic wall. After surgery the patient recovered quickly and no rebleeding recurred.Identification of the exact origin of lower gastrointestinal tract bleeding remains difficult. As the mortality rate as well as the re-bleeding rate in blind segmental colectomy is very high, compared to the resection in patients, where bleeding site could be identified, the site of bleeding must found in any case.

A 57-year-old woman complained about increasing pain and weakness in her hips and legs. 7 months earlier active (Crohn's) ileocolitis had been diagnosed. She had received several bouts of steroids and had been in clinical remission for 12 weeks under a dosage of 40 mg/d prednisone.Clinical examination, laboratory work up, x-rays and MRI of the pelvis, bone scan, neurologic examination and muscle biopsy showed unspecific results. THERAPY AN COURSE: Steroides were tapered and replaced by weekly intramuscular methotrexate 20 mg which resulted in long lasting clinical remission. Pain and weakness persisted. 6 months later MRI revealed osteonecrosis of both femoral heads. 4 1/2 years after the initial diagnosis of Crohn's disease the patient complained about pain in her lower legs without evidence of osteonecrosis in MRI. Another 2 years later avascular osteonecrosis was diagnosed by tibial bone biopsy. Now MRI verified patchy osteonecrosis of the tibiae. Further osteonecrosis of the left foot were diagnosed by MRI ten years after initial diagnosis of Crohn's disease in the now 67-year-old patient. She is still in remission on weekly intramuscular 15 mg methotrexate.The long interval between steroid treatment and recurrent avascular bone necrosis as well as the unusual pattern of bone involvement indicate that osteonecrosis is an extraintestinal manifestation of Crohn's disease. More reports and comparative studies are necessary to give more evidence that avascular osteonecrosis is an extraintestinal manifestation of inflammatory bowel disease.

The determinants of the placebo effect are not well established. Goal of this study was to explore likely predictive factors in an already published data set.We re-analysed data from a study in 120 patients with the irritable bowel syndrome (IBS) that were randomly assigned to three arms of the study to receive (double-blind) either a drug (mebeverin) (n = 40) or placebo (n = 40), or (in an open trial) dietary treatment (fibre) (n = 40) for up to 16 week. Treatment was conducted by 3 different doctors (A, B, C) with 44, 27, and 18 patients, resp. A fourth group (n = 31) was treated by different varying physicians. Symptoms were assessed every 4 weeks, and the degree of patient compliance and the number of drop-outs, the number of patients improved/not improved (in %), symptom severity (Kruis Score) at enrolment, and age and gender as covariates were included into the analysis.Drop-out rate was 30 % for placebo, 30 % for mebeverin, and 15 % for the diet. For the patients remaining in the study, average compliance was 75 % with placebo, but 89 % for the drug and 82 % for the diet. Response rates were 39 % for placebo, but 20 % for the drug; response rate for the diet (open trial) was 43 % under all doctors. Response rates for drug and placebo combined were 32 % for doctor A (female,43 years), but 19 % for doctors B and C together (both males, 32 and 40 years)); this effect was not significant. Placebo responders were more often women (47 %) than men (28 %), while age effects were only found with dietary treatment: responders were younger. Placebo responders had an overall lower Kruis Score than non-responders (45 vs 52 points), but this was also true for drug (52 vs. 62 points) and diet responders (56 vs 68 points).The major factors contributing to the placebo response are the treating physician (gender, training), and the patients gender (female). Patients with lower Kruis score (more likely non-functionally disordered) may be prone to higher (placebo) response rates.

Hymecromone (4-methyl-umbiliferone) has been used for more than 20 years for the treatment of functional and obstructive spasms of the biliary tract. Its mode of action however is still largely unknown. We investigated the effect of 4-methyl-umbiliferone p. o. and i. v. on gall bladder and common bile duct motility and studied potentially indirect effects via alterations in bile acid metabolism.Twenty healthy volunteers, aged 25 - 37, 10 males, 10 females, were included into a Placebo-controlled, randomised, cross-over double-blind study. Subjects were treated with 800 mg hymecromone p. o.; in addition a standardized meal (Biloptin, 40 gs) was given. Gall bladder volume and common bile duct diameter were determined by ultrasound. Conjugated and unconjugated bile acids were analysed by gas chromatography. Additionally, in a third open label phase hymecromone was given i. v.Common bile duct diameter was significantly larger after a standard meal with hymecromone given p. o. or i. v. than with placebo (each p0.01). However, alterations in gall bladder volume after a standard meal were not different between placebo and hymecromone (p. o. or i. v.). Unconjugated and conjugated bile acids rose after standard meal in all three groups without significant differences between hymecromone and placebo.Hymecromone was associated with significant dilation of the common bile duct. In contrast to previous reports an effect of hymecromone on gall bladder motility could not be observed. The unchanged values of bile acids in serum after hymecromone compared to placebo, together with the dilatation of the common bile duct after hymecromone, may indicate a bile acid-independent effect of hymecromone on bile secretion.

Alterations in the colon wall, motility disorders, and certain nutritional habits are the essential factors in the development of colon diverticula. Thus, with advancing age this results in a high incidence in Western industrialized countries. The clinical picture is usually one of symptom-free diverticulosis. Diverticular disease can be associated with minor symptoms, but in complicated cases with diverticulitis and diverticular hemorrhage, it is potentially fatal. Further complications include abscess formation, fistula development, and obstruction. Barium double-contrast imaging exhibits the highest diagnostic sensitivity in diverticulosis but is contraindicated in cases of suspected complicated diverticular disease due to the danger of perforation. In these instances, sonography, computed tomography, or magnetic resonance imaging are performed. For diverticular hemorrhage, coloscopy not only represents a possible diagnostic tool but also a therapeutic option for various techniques of hemostasis. Treatment of diverticulitis and its complications requires careful consideration of conservative and surgical approaches and close interdisciplinary cooperation.

Treatment with antibiotics in inflammatory bowel disease has a long tradition and is widely used. The indications for antibiotic therapy are wide ranging, from specific situations such as abscesses or fistulae, to patients with severe disease (as an unspecific 'protective' measure), and to address the hypothesis that the enteric flora as a whole, or specific microorganisms such as mycobacteria, are involved in the pathogenesis of inflammatory bowel disease. The best-studied single antibiotic compound is metronidazole. However, overall, the scientific basis for the use of antibiotics is limited, which may reflect a lack of interest from sponsors within the pharmaceutical industry. Despite this weak evidence base, antibiotics are a globally established therapeutic tool in inflammatory bowel disease. Growing evidence from human and animal studies points towards a pivotal pathogenetic role of intestinal bacteria in inflammatory bowel disease. In view of these experimental findings, clinical trials have been undertaken to elucidate the therapeutic effects of probiotics in inflammatory bowel disease. Probiotics are viable nonpathogenic microorganisms which confer health benefits to the host by improving the microbial balance of the indigenous microflora. So far, of the many candidates, one specific strain (Escherichia coli Nissle 1917) and a mixture of eight different bacteria have demonstrated convincing therapeutic efficacy in controlled studies. Maintenance therapy in ulcerative colitis and prevention therapy, as well as the treatment of pouchitis, have emerged as areas in which probiotic therapy offers a valid therapeutic alternative to current treatments. Further investigations may detect additional clinically effective probiotics and other clinical indications.

The aim of this article is to review potential antineoplastic properties of anti-inflammatory compounds commonly used in various inflammatory diseases such as aminosalicylates, aspirin and other nonsteroidal drugs. Starting from experimental and epidemiologic evidence showing prophylaxis and/or tumor regression/suppression, specific antineoplastic actions especially the inhibition of cyclooxygenase-(COX)dependent and COX-independent steps including the role of transcription factor (NFkappaB) in the cell cycle regulation are reviewed. In addition other mechanisms by which these drugs may exert antitumor effects, also may be important such as induction of apoptosis of cancer cells and/or inhibition of potentially carcinogenic oxidative DNA damage. Based on this knowledge potential clinical implications are discussed.

Recombinant T-cell receptors with antibody-like specificity for tumor-associated antigens are successfully used to direct the cytolytic activity of T cells toward tumor cells. Clinical application, however, needs to comply with the low immunogenicity of the recombinant receptor, efficient gene transfer into peripheral blood T cells, and enrichment of receptor-grafted cells. Here, we address these issues and describe an entirely humanized immune receptor for use in adoptive immunotherapy of colorectal carcinoma. The receptor consists of a single-chain antibody (scFv) binding domain specific for carcinoembryonic antigen (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and intracellular CD3 zeta signaling chain. To express the receptor in peripheral blood T cells, both GALV envelope and MuLV 4070A pseudotyped retrovirus turned out to be equally efficient, with transduction efficiencies of about 5% to 40%, depending on the lymphocyte donor. Furthermore, receptor-grafted T cells could be 2- to 6-fold enriched by magnetic activated cell sorting, utilizing an antibody directed to the extracellular IgG domain of the receptor. Upon co-culture with CEA(+) tumor cells, receptor-grafted T cells are specifically and efficiently activated to cytolysis and IFN-gamma secretion, demonstrating their feasibility for the adoptive immunotherapy of CEA(+) carcinomas.

Crohn's disease (CD) and ulcerative colitis (UC) are clinical entities characterized by spontaneous relapses and are thought to be caused in large part by a dysregulated immune response to inflammatory stimuli. Specific infectious agents or antigens inducing or perpetuating inflammation, however, are not known. Recent results in contrast support the hypothesis, that the normal intestinal flora plays a central role in the pathogenesis of both diseases. Studies performed with E. coli Nissle 1917 demonstrated that this bacterium can positively affect the course of disease in UC and CD patients. The clinical efficacy of probiotics can yield valuable information about disease pathogenesis and, as a modification of current standard therapy, opens new and interesting therapeutic alternatives.

Inflammatory bowel disease (IBD) has a definite genetic component as documented by epidemiological and linkage evidence. It shows an earlier onset of disease in children of affected patients than in their parents. This has lead to speculations about genetic anticipation in this disorder. 2,007 IBD patients with sporadic disease and 472 multiplex familial cases (including 103 affected parents and 99 children of affected patients) were evaluated with a multi-item questionnaire as part of a study of inflammatory bowel disease genetics. The Mann-Whitney U-test and the general linear model were used for analysis. Clinical characteristics such as presence of fistulae, stenoses, extraintestinal manifestations, and other parameters, which are related to the severity of the disease, were found to be similar between familial and sporadic cases of IBD (corrected Por = 0.31 for all tests). The mean-age-of onset in children of affected patients was 19.4 years earlier than in their parents. However, the age of the parental cohort was significantly higher (27 years) and the diagnostic interval also longer (1.7 years). If these confounders are corrected in a general linear model, no significant difference is evident for the age-of-onset between the groups (Por = 0.52). There is no evidence for genetic anticipation in inflammatory bowel disease. The absence of genetic anticipation is consistent with the clinical similarity of familial and sporadic inflammatory bowel disease. This finding justifies the primary genetic analysis of familial disease under the assumption that their genetic background will be representative for all presentations of IBD.

Colorectal cancer represents the major cause for excess morbidity and mortality by malignant disease in ulcerative colitis as well as in Crohn's disease. The risk for ulcerative colitis associated colorectal cancer is increased at least 2-fold compared to the normal population and colorectal cancer is observed in 5.5-13.5% of all patients with ulcerative colitis and 0.4-0.8% of patients with Crohn's disease. Established risk factors include long duration of the disease, large extent of the disease, low activity of the disease, young age at onset, presence of complicating primary sclerosing cholangitis or stenotic disease and possibly lack of adequate surveillance, inadequate pharmacological therapy, folate deficiency and non-smoking. Crohn's disease is associated with an increased risk of colorectal carcinoma in patients with long-standing disease, strictures and fistulae under the condition that the colon is involved, tumors of the small intestine may occur occasionally. Extracolonic malignancies are rare, with the exception of biliary tract cancer. Ulcerative colitis associated colorectal cancer typically can occur in the entire colon, is often multifocal and of undifferentiated histology. Stage distribution and prognosis of ulcerative colitis associated colorectal cancer appears to be similar to that of sporadic colorectal cancer with an overall survival of about 40% (15-65%) after 5 years with tumor stage at diagnosis being the most important predictive parameter for survival. Tumor markers helpful for the diagnosis of sporadic colorectal cancer fail to differentiate between inflammatory response and malignant transformation. In contrast the histologic evidence of dysplasia was shown to be a strong indicator of underlying carcinoma or developing malignant transformation. The presence of a surface projection termed dysplasia associated lesion or mass is highly indicative of underlying or associated cancer. While the routinely performed search for dysplasia is hampered by high interobserver variation the demonstration of DNA-aneuploidy or genetic changes which may confirm the ongoing malignant transformation has not yet become clinical routine. The genetic alterations found in ulcerative colitis associated colorectal cancer involve many of the same targets found in sporadic colorectal tumors and include multiple sites of allelic deletion, microsatellite instabilities, and mutations of APC, p53, Ki-ras as well as MSH2 and other genes. The progression of dysplasia to carcinoma is generally accompanied by an accumulation of these mutations and the similarities in the biology of colorectal cancer associated with ulcerative colitis and sporadic colorectal cancer appear to outweigh their difference. In regard to the management of dysplasia and cancer, the role of surveillance programs for the early detection of ulcerative colitis associated colorectal cancer at a curable stage is still under debate. Although these programs failed at tumor prevention and lethal carcinomas are still found inadvertently in patients under surveillance, the majority of surveillance programs could reduce mortality by detecting more cancers at a still curable stage. Current recommendations for surveillance include, therefore, biennial colonoscopy with extensive biopsies after 8-10 years of total colitis or after 15-20 years of left-sided colitis. In the presence of cancer or unequivocal high-grade dysplasia and/or dysplasia associated lesion or mass proctocolectomy is considered adequate. The evidence of low-grade dysplasia should be confirmed before proctocolectomy is considered.

Bile acids are believed to be involved in the formation of colonic cancer, and 5-aminosalicylic acid and other salicylates may have a protective role. The precise mechanisms of both actions are not known, but modifications (stimulation or inhibition) of basal or oxygen-radical induced DNA base hydroxylation as potential early events in tumor formation by these compounds may be involved in such actions. We, therefore, investigated whether: (1) bile acids in concentrations as they occur systemically or intraluminally are able to enhance basal or OH*-radical-stimulated base hydroxylation in DNA from calf thymus; (2) 5-aminosalicylic acid, its main intestinal metabolite N-acetyl-aminosalicylic acid and salicylate, the main aspirin metabolite, are able to inhibit this hydroxylation; and (3) DNA from calf thymus can be used as a model by comparing its base composition and hydroxylation with DNA from normal human colonic mucosa. We found an enhancement of the OH*-radical-induced DNA hydroxylation especially 8-OH adenine with 214.0%. On the other hand 5-ASA, N-acetyl-ASA, and salicylate showed a concentration-dependent inhibition of OH*-stimulated hydroxylation with IC50 between 0.04 +/- 0.01 mM (X +/- SD) and 1.3 +/- 0.1 mM. No effects were observed on basal hydroxylation. Electron spin resonance spectroscopy studies showed reduction of the corresponding base signals pointing to a scavenger mechanism. In DNA isolated from normal human colonic mucosa (N = 7) a similar base distribution was found as in calf thymus; hydroxylation wasor = 1.0% in both systems. From our results we conclude that DNA from calf thymus may serve as a model for human colonic mucosal DNA and that one of the carcinogenic actions of bile acids may be enhancement of oxygen-radical-induced DNA base hydroxylation, especially 8-OH adenine. The absence of effects under unstimulated conditions supports their role as cocarcinogens. The concentration-dependent inhibition of OH*-stimulated DNA hydroxylation by 5-ASA, salicylate, and N-acetyl-ASA may be a possible mechanism of chemoprevention.

Sulfasalazine (SASP), since 60 years standard in the treatment of ulcerative colitis, is a double molecule where 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) are linked together by an azobond. Bacterial splitting of SASP within the colon allows delivery of 5-ASA for its topical action (prodrug system). To target 5-ASA without the less tolerable SP down to the lower intestine new prodrugs have been developed and, in addition, mesalazine is offered which contains 5-ASA prepared as a delayed release preparation. A clinical comparison (metaanalysis) tended towards superiority of the new prodrugs and mesalazine over SASP for inducing remission, while SASP was more effective in maintaining remission. Only few studies exist comparing the efficacy of the new drugs and mesalazine. To date a slight superiority of the new prodrugs is implied. With the exception of SASP safety profiles do not significantly differ between the different drugs containing 5-ASA.

Alpha-interferon (IFN-alpha) is an effective treatment for chronic hepatitis B but only 25-40% of patients will profit from a long-term beneficial response to the currently recommended schedule of 3-6 MU given 3 times a week for 6 months. Clinical trials are therefore needed to investigate alternative modifications of interferon therapy, including combinations of different antivirals or immune modulators in order to improve the therapeutic approach to chronic hepatitis B infection. In a phase II trial we evaluated whether a combination of natural interferon-beta (nIFN-beta) with strong antiviral activity plus recombinant interferon-gamma (rIFN-gamma) with a predominantly immunomodulatory activity is able to increase the response rate compared to historical controls treated with IFN-alpha in a conventional regimen.Forty patients with chronic hepatitis B were included in this trial of combined interferon therapy at a dosage of 6 MU nIFN-beta during week 1 followed by 3 MU for weeks 2-4 plus rIFN-gamma at a daily subcutaneous (s.c.) injection of 150 microg during the entire 4 weeks of the treatment period. Patients entered the trial on the basis of the following criteria: hepatitis B surface antigen (HBsAG), HBeAG and HBV-DNA positive for at least 6 months, HDV, EBV, CMV, anti-HIV negative, and chronic hepatitis proven on biopsy taken within 4 weeks of entry as well as 6 and/or 12 months after interferon therapy. The final diagnosis and classification of chronic hepatitis has been based on guidelines according to a revised classification of chronic hepatitis (Desmet 1994). The post-treatment follow-up was 12 months.The combined interferon therapy achieved complete responses with seroconversion from HBeAG to anti-HBe and a negative HBV-DNA (dot blot) test, as well as normalization of ALT activity in 15 patients, and partial response with negativation of HBV-DNA concomitant to a decrease in aminotransferase activity to near normal levels in 6 patients. Nineteen patients showed no response to viral markers but showed relief of clinical symptoms as well as pronounced decrease of serumtransaminase activity. Grading of liver biopsies demonstrated an improvement of histologic parameters after the interferon regimen in half of the evaluable patients (n=22). Histological response has been quantified by a reduction in the score of histological activity (HAI-index) from 12.6 before to 7.6 after interferon therapy, and in the inflammation and cellular degeneration score (ICD) from 9.9 to 5.2. Histological response, however, failed to show a consistent correlation with serologic response. This medium-dose combination of interferon-beta and interferon-gamma was tolerated very well by the patients, this good tolerability being explained by tachyphylaxis in response to daily interferon doses. No serious side effects or decompensation of liver function were observed during the 4-week period of therapy or the follow-up, despite the special clinical situation where 60% of the patients included in the study presented with histologically proven cirrhosis (35% of them with clinical manifestation of mildly decompensated cirrhosis).This short-term regimen of combined nIFN-beta + rIFN-gamma therapy in patients with chronic hepatitis B proved to be equieffective to long-term treatment with interferon-alpha and combines high clinical tolerability with good practicability, as it can be administered on an in-patient basis, ensuring close patient monitoring.

Glucocorticoids, even when administered topically, have a known early benefit on diarrheal symptoms in inflammatory bowel diseases which may not be explained exclusively by their anti-inflammatory effect. Therefore, we evaluated a possible early effect of topically administered glucocorticosteroids on the mucosal function of patients with distal inflammatory bowel disease in a prospective, controlled study, which was blinded for histological evaluation.Eleven patients with distal ulcerative colitis or Crohn's disease, and 8 patients without intestinal inflammation were studied. A sigmoidoscopy with biopsy sampling (8-10) was performed before and 3 days after rectal administration of a hydrocortisone acetate foam preparation (100 mg b.i.d.). Prior to and after topical steroid treatment, basolateral (Na++K+)-ATPase activity (coupled optical assay), specific 3H ouabain binding (rapid filtration method), 5'-nucleotidase (microdetection method of phosphorus), and mucosal DNA levels (diphenylamine reaction) were determined from biopsy homogenates. Morphological and clinical characteristics were assessed according to established scores.Short-term topical GCS treatment significantly (p0.05) stimulated (Na++K+)-ATPase activity (103%) as well as the number of active (Na++K+)-ATPase molecules (190%). In the healthy mucosa, only (Na++K+)-ATPase activity was stimulated (124%, p0.05; specific 3H ouabain binding: 33%; p=0.09). As an unspecific GCS effect, apical 5'-nucleotidase was also stimulated (p0.05; IBD: 50%; controls: 200%). As assessed by endoscopic and histological scores, as well as by mucosal DNA levels, morphological signs of intestinal inflammation remained unchanged during the study, whereas the daily stool frequency decreased significantly (p0.05).In patients with distal inflammatory bowel disease, short-term treatment with topical GCS leads to a quick recovery from diarrheal symptoms, due to the early improvement of mucosal function prior to the occurrence of the well-known anti-inflammatory GCS effect.

To compare the efficacy and tolerability of olsalazine sodium with enteric-coated mesalazine in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis.Patients with mild to moderate active ulcerative colitis were randomized to receive either olsalazine sodium, 3 g/day (n = 88), or mesalazine, 3 g/day (n = 80), for up to 12 weeks.Of the patients treated with olsalazine sodium, 52.2% achieved endoscopic remission, compared with 48.8% of patients treated with mesalazine. This difference was not significant (P = 0.67). There was a nonsignificant trend for patients with left-sided colitis or a more severe endoscopic grade to achieve remission if they were treated with olsalazine sodium than if they were treated with mesalazine. Both treatments were comparable with respect to clinical activity index and an investigator's global assessment. Seventy patients reported one or more adverse events; adverse events were seen in 45% of olsalazine sodium-treated patients and in 36% of mesalazine-treated patients. Eleven patients treated with olsalazine sodium and nine patients treated with mesalazine withdrew from the study because of adverse events. One patient treated with olsalazine sodium compared with two treated with mesalazine stopped treatment because of diarrhoea. Serious adverse events occurred in three patients treated with olsalazine sodium and in four treated with mesalazine.Therapeutic effectiveness and tolerance to the treatment did not differ between olsalazine sodium, 3 g/day, and mesalazine, 3 g/day, in inducing endoscopic remission in patients with mild to moderate active ulcerative colitis within 12 weeks of treatment.

The poor prognosis of advanced gastric carcinoma requires new therapeutic approaches. Among these, the specific activation of resting lymphocytes by bispecific antibodies may be promising. Here we describe the generation and function of a bispecific monoclonal antibody (bi-mab) with specificity for CD3 and for the tumor antigen CA72-4 (TAG72) on various gastrointestinal tumors. We established a hybrid/hybridoma by somatic fusion of two hybridoma lines secreting antibodies against CA72-4 and CD3 respectively and characterized its bimab OKT3/B72.3. In combination with costimulatory anti-CD28 antibodies resting peripheral lymphocytes could be activated specifically by bi-mab OKT3/B72.3 with T cell proliferation and IL-2 secretion. The bi-mab OKT3/B72.3 could also trigger the cytotoxicity of these T cells toward, CA72-4+ cells in vitro. Our results indicate, that bi-mab OKT3/B72.3 in combination with an anti-CD28 mab can redirect T cell cytotoxicity specifically against CA72-4+ tumor cells implicating a novel strategy for the specific immunotherapy of CA72-4+ tumors.

Summary Infection with Helicobacter pylori causes chronic active gastritis and has been associated with gastric and duodenal ulcer disease. In biopsy samples of 110 patients with clinical symptoms of active gastritis, H. pylori was detected by means of the polymerase chain reaction (PCR), using species-specific primers defining a 858 by DNA fragment of H. pylori urease βsubunit. Sensitivity and specificity of the PCR was compared with culture, histology and Warthin-Starry stain (WSs), detection of H. pylori urease antibodies in serum and urease testing with the Campylobacter-like organism (CLO) test. PCR yielded specific amplification products in 53 cases, whereas culture of the organisms was positive in a subset of 50 cases. Only direct detection in histological sections of biopsy specimens had a higher sensitivity, with 65 positive samples. In contrast, the CLO test was negative in eleven culture-positive and PCR-positive cases. Significant urease antibody titres were found in 39 patients with histologically confirmed diagnosis. These results placed the sensitivity of PCR between that of the Warthin-Starry stain (WSs) and that of culture. Therefore, PCR can be proposed as a useful rapid and time-saving technique for the detection of H. pylori in gastritis. For epidemiological purposes, fingerprinting with arbitrarily chosen primers by AP-PCR was evaluated. Strain-specific patterns with up to 13 fragments were achieved with 10nucleotide or longer primers (21-nt) with a G+C content ≥ 55%. Thirty-five of 40 strains investigated by this method were distinguishable with a single primer. These results suggest a high level of DNA sequence diversity within this species with the possibility of confirming the clonality in consecutive isolates from a single individual. Alternatively, an increased in-vivo mutation rate could be responsible for DNA divergence, resulting in specific strains for each individual patient.

Chronic diarrhea, defined by frequent bowel movements with decreased stool consistency lasting for longer than 3 weeks represents a major problem in gastroenterology. In addition to the very frequent functional disturbances of irritable bowel syndrome a wide variety of infectious, drug-induced, alimentary, metabolic, hormonal and organic causes requires a thorough evaluation of this symptom. To reach diagnosis an algorithm applying a wide array of diagnostic procedures based on the results of thorough anamnesis, physical examination and stool visit should be followed. In addition to alleviation of symptoms, reconstitution and prevention of nutrional deficits (volume, electrolytes, trace elements, vitamines, calories) therapeutic approaches should eliminate underlying causes whenever possible. Symptomatic relief is provided by substances inhibiting secretion and motility as the opiatagonist Loperamid or anticholinergics. Substitution of vitamins, trace elements, calories, enzymes or bile salts should be adapted to the individual needs. Elimination of a cause of chronic diarrhea is generally provided be anti-infectious therapy, other causes however (e.g. sprue by the elimination of gliadin from diet) may be treated effectively as well.

To determine the therapeutic efficacy and safety of three doses of olsalazine compared with the standard dose of sulphasalazine.Randomized double-blind multicentre 6-month study comparing three doses of olsalazine (0.5, 1.25 and 2.0 g daily) and sulphasalazine 2.0 g daily for maintaining remission in patients with ulcerative colitis.Public hospitals and private practices in Germany, Austria and Switzerland.A total of 162 patients with ulcerative colitis in remission.According to intention-to-treat analysis, the failure rates of the different treatment groups were not significantly different (36, 49 and 24% for 0.5, 1.25 and 2.0 g olsalazine daily and 32% for 2.0 g sulphasalazine daily). Olsalazine and sulphasalazine showed a tendency towards lower failure rates in extended (28%) than in distal disease (44%). The withdrawal rate due to adverse effects was 4%, the most frequent single event being diarrhoea (2.5, 5.2 and 11.7% for 0.5, 1.25 and 2.0 g olsalazine daily and 0% for sulphasalazine daily).This study found no significant differences between the therapeutic efficacy or safety of 0.5-2.0 g olsalazine daily. Because of its sulpha-free formulation olsalazine may, however, be preferred to sulphasalazine.