[Adalimumab for the treatment of ulcerative colitis--a consensus report by the working group inflammatory bowel diseases of the Austrian Society of Gastroenterology and Hepatology]. / Adalimumab in der Behandlung der Colitis ulcerosa--ein Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

TNF alpha antibodies have clearly improved the outcome of moderately to severely active ulcerative colitis. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which is administered subcutaneously. Since April 2012 adalimumab is approved for the treatment of moderately to severely active ulcerative colitis in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Adalimumab can induce and maintain clinical remission and mucosal healing compared to placebo in moderately to severely active ulcerative colitis, can reduce the rate of ulcerative colitis related hospitalisations and improve health-related quality of life. The response can be observed after two weeks of treatment. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Studies on the treatment of ulcerative colitis with adalimumab did not reveal new safety aspects. The present consensus report by the Working Group Inflammatory Bowel Diseases of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence of adalimumab for the treatment of ulcerative colitis and is aimed to assist as code of its practice.

[Adalimumab for the treatment of adult Crohn's disease--update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology]. / Adalimumab in der Behandlung des adulten Morbus Crohn--Update eines Konsensus der Arbeitsgruppe Chronisch Entzündliche Darmerkrankungen der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie.

TNF alpha antibodies have clearly improved the outcome of moderate to severe Crohn's disease. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which can be self-administered subcutaneously. Since August 2012 adalimumab is approved for the treatment of moderately to severely active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Compared to placebo adalimumab can induce significantly more often steroid-free remission and mucosal healing in patients with moderate to severe Crohn's disease, reduce the rate of Crohn's disease-related hospitalisations and surgery and improve health-related quality of life. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to TNF-alpha antibodies and in those previously exposed with a rapid onset of action within days and confirmed maintenance performance over 3 years. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to its low immunogenicity allergic reactions are rare. The update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence on adalimumab for the treatment of Crohn's disease and is aimed to assist as a code of practice in its applications.

Knotting of percutaneous endoscopic jejunostomy feeding tubes in two patients with Parkinson's disease and continuous Duodopa® treatment.

Continuous intraduodenal infusion of levodopa/carbidopa (Duodopa®) via PEJ tubes is increasingly used in patients with advanced stages of Parkinson's disease. Tube-related complications such as kinking or coiling have been frequently reported. We herein describe two cases of tube dysfunction in patients with Parkinson's disease and continuous Duodopa® treatment due to knotting of the distal end of the tube. The mechanisms of knotting are unclear although a causative role of impaired gastrointestinal motility either by Parkinson's disease itself or Duodopa® treatment might be suspected.

[Diagnosis and treatment of iron deficiency and anaemia in inflammatory bowel diseases. Consensus of the Austrian IBD Working Party]. / Diagnose und Behandlung von Eisenmangel und Anämie bei chronisch entzündlichen Darmerkrankungen. Konsensus der österreichischen Arbeitsgruppe für CED.

Iron deficiency with and without anaemia is a common burden of patients with inflammatory bowel diseases (IBD) and has considerable impact on their quality of life and the ability to perform. The IBD working group of the Austrian Society of Gastroenterology and Hepatology developed five consensus statements on the following topics: (i) diagnosis of iron deficiency and (ii) anaemia, (iii) screening of iron deficiency, (iv) treatment of iron deficiency and (v) therapeutic goals. The clinical importance of intravenous iron replacement therapy in IBD with regard to effectiveness and compliance was discussed.

[Infliximab therapy for Crohn's disease - a practical guideline: actualised consensus of the working group for chronic inflammatory bowel diseases of the Austrian Society for Gastroenterology and Hepatology]. / Infliximab in der Therapie des Morbus Crohn - ein praktischer Leitfaden: aktualisierter ÖGGH-Konsensus der Arbeitsgruppe Chronisch-entzündliche Darmerkrankungen der ÖGGH.

Infliximab is a monoclonal antibody against tumor necrosis factor alpha (TNF-α), which is approved for the treatment of chronic inflammatory bowel disease (IBD) such as Crohn's disease (CD), fistulating Crohn's disease (FCD), ulcerative colitis (UC), and paediatric ulcerative colitis (PUC) from 6 years onwards. Besides its therapeutic efficacy, this antibody therapy is characterised by its side effects profile, which has been addressed in a seperate consensus statement by the Working Group for chronic inflammatory bowel diseases within the Austrian Society for Gastroenterology and Hepatology. Infliximab is an effective treatment option for the above-mentioned indications; however, use of this agent requires special knowledge to assess the benefit-risk profile for each patient individually.

The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis.

BACKGROUND: Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown. AIMS: To establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success. METHODS: This is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre-treatment (FMT-group, n = 17) vs antibiotic pre-treatment only (AB-group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene-based microbiota analysis. RESULTS: In the FMT-group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB-group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness. CONCLUSIONS: The taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.

The efficacy and safety of either infliximab or adalimumab in 362 patients with anti-TNF-α naïve Crohn's disease.

BACKGROUND: TNFα antagonists, including infliximab (IFX) and adalimumab (ADA), have revolutionised treatment for Crohn's disease. Studies comparing efficacy in patients with Crohn's disease naïve to TNFα antagonists are lacking. METHODS: Consecutive TNFα antagonist-naïve patients with luminal or perianal Crohn's disease from four tertiary centres in Austria were assessed prospectively for induction and maintenance efficacy, and safety, of either IFX or ADA. RESULTS: In a total of 362 patients, 251 (69.3%) started IFX and 111 (30.7%) started ADA. At baseline, the median Harvey-Bradshaw Index (HBI) score was 8 (range 5-29) and 8 (5-36), and the median C-reactive protein (CRP) was 1.07 (interquartile range (IQR) 1.36) mg/dL and 1.16 (IQR 1.23) mg/dL for IFX and ADA, respectively. At week 12, there was no difference between IFX and ADA among patients with luminal Crohn's disease in clinical remission (IFX 128/204; 62.7% vs. ADA 68/107; 63.6%, P = 0.47), clinical response (IFX 154/204; 75.5% vs. ADA 82/107; 76.6%, P = 0.82) and steroid-free remission (IFX 110/204; 53.9% vs. ADA 61/107; 57%, P = 0.60). At 12 months, there were similar numbers of patients treated with IFX and ADA who maintained clinical remission (IFX 77/154; 50.4% vs. ADA 47/82; 57.3%, P = 0.48) and steroid-free remission (IFX 68/154; 44.3% vs. ADA 44/82; 53.7%, P = 0.16). Baseline CRP >0.7 mg/dL (OR 0.24; 95% CI 0.07-0.77, P = 0.01) was the only predictor of clinical remission at 12 months in patients who did not have escalation of anti-TNFα therapy. CONCLUSION: IFX and ADA appear comparable in clinical outcomes for patients with Crohn's disease who are naïve to TNFα antagonists.

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.

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.

Effect of pancreatic polypeptide on the motility of the guinea-pig small intestine in vitro.

The effect of porcine pancreatic polypeptide (PP) on the motor activity of the longitudinal and circular muscles of the guinea-pig isolated small intestine was investigated. PP (0.2-20 nM) inhibited cholinergic contractions of the longitudinal muscle in response to electrical field stimulation, the maximal effect being a 30% reduction of the contraction amplitude. Carbachol-induced contractions of the longitudinal muscle were not affected by PP (10 nM). PP (0.3-30 nM) also inhibited reflex contractions of the circular muscle elicited by balloon distension and recorded orally to the site of distension; the maximal effect was a 80% reduction of the reflex contraction. In contrast, carbachol-induced contractions of the circular muscle remained unaltered by PP (10 nM). It was further found that PP (10 and 100 nM) enhanced the threshold intraluminal pressure at which peristaltic waves were triggered. All these effects of PP appeared to be transient. Taken together, these data indicate that PP does not act on intestinal smooth muscle but can modulate the activity of certain enteric neurones which are involved in the regulation of intestinal motility.

Absorption of hydrolysed bovine serum albumin from the human jejunum over a 6-hour period.

OBJECTIVE: Quantitative assessment of intestinal absorption of total and single amino acids in a hydrolysed bovine serum albumin solution over a 6-h period. DESIGN: Ten healthy volunteers underwent segmental jejunal perfusion using a multi-lumen tube assembly with a proximal occluding balloon. Prehydrolysed bovine serum albumin served as protein source. In one set of experiments we used a washout phase before the equilibration period to eliminate any contents present in the test segment. In another set we started directly with the equilibration period. Absorption rates of total and single amino acids were measured over a period of 6 h. RESULTS: Absorption rates remained constant throughout this period and there was no significant difference in absorption rates whether a washout phase was used or not. Absorption rates of total amino acids ranged from 6.4 +/- 1.9 (mean +/- SEM) to 10.7 +/- 0.7 g/h and 30 cm, when a washout phase was used. Percentage absorption of the perfusion load per hour was 24 +/- 7% to 40 +/- 2% with a washout phase. Although a highly concentrated perfusion load was used there was a correlation (r = 0.66, P < 0.05) between absolute concentration in the perfusion solution and the amount of individual amino acid absorbed. Individual amino acids showed a wide range of percentage absorption. Percentage absorption of 50% or more of the perfusion load was seen for alanine, phenylalanine, arginine, leucine, methionine and tyrosine. The highest absorption rate was seen for methionine with 86%, the lowest for cysteine with 3%. CONCLUSION: When hydrolysed bovine serum albumin is used, amino acid absorption is constant over a period of 6 h in the human jejunum. A washout phase has no influence on total and single amino acid absorption.

Acetorphan prevents cholera-toxin-induced water and electrolyte secretion in the human jejunum.

OBJECTIVES: Acetorphan is an orally administered inhibitor of enkephalinase in the wall of the digestive tract. It prevents inactivation of endogenous opioid peptides released by submucosal and myenteric neurons. The aim of this study was to examine the effect of acetorphan on jejunal water and electrolyte transport in healthy volunteers under basal conditions and in a state of intestinal secretion induced by a bacterial enterotoxin. DESIGN: Ten volunteers in two groups were studied in an open trial. For the experimental design an intestinal perfusion technique was used. METHODS: Cholera toxin was used to induce intestinal secretion in a model employing segmental perfusion of the human proximal jejunum. Acetorphan was given orally prior to intrajejunal administration of cholera toxin; its effect on intestinal transport was measured over a period of four hours after exposure to cholera toxin. Serum levels of methylthioether of thiorphan as the main metabolite were measured throughout three experiments to assure sufficient drug absorption. RESULTS: Acetorphan had no influence on basal water and electrolyte absorption (133 vs. 140 ml/30 cm x h). In a control group with cholera toxin alone, significant water secretion was induced (131 ml/30 cm x h). Acetorphan completely prevented this secretion by leaving an absorption rate of 27 ml/30 cm x h. Intestinal electrolyte transport was also significantly changed towards absorption by acetorphan. CONCLUSION: Acetorphan can prevent jejunal water and electrolyte secretion induced by cholera toxin. Enkephalins may thus protect the small intestine from enterotoxin-induced secretion.

[Sonography and cytology of cold thyroid nodules]. / Sonographie und Zytologie von kalten Schilddrüsenknoten.

270 patients with a scintigraphically cold thyroid nodule of sonographically increased (n = 34), diminished (n = 72) or neutral (n = 86) echogenity or cystic criteria (n = 78) were subjected to fine needle aspiration biopsy. This revealed unequivocal malignancy in 8 and follicular neoplasia in another 30 patients, 10 of whom proved to have malignomas on further evaluation. A total of 12 papillary and 2 follicular carcinomas, 2 non-Hodgkin lymphomas, 1 sarcoma and the metastasis of a breast carcinoma were diagnosed. The most sensitive criteria for malignancy were diminished echogenity, an inhomogeneous echo pattern and the occurrence of a solitary nodule. The incidence of malignancy was increased among males but not among especially young persons. There was no sonographic feature that would permit omission of fine needle aspiration.

[Is sonography superior to enzyme diagnosis in the detection of hepatic steatosis?]. / Ist die Sonographie der Enzymdiagnostik bei der Erkennung der Steatosis hepatis überlegen?

In order to evaluate the diagnostic value of sonography in steatosis of the liver, liver biopsies were performed in 52 patients with sonographically diagnosed steatosis of the liver. 27 of 28 patients with normal serum enzymes showed an estimated steatosis of 10 to 40% on histological examination. In the other 24 patients with increased serum enzyme levels histological steatosis was found in 20 patients. 8 further patients with presumed systemic disorders had both normal sonographic findings and normal serum enzyme levels and when subjected to liver biopsy showed an estimated steatosis in the range of 5 to 10%. Reliable sonographic diagnosis of steatosis of the liver can be made only if the degree of steatosis exceeds 10% at least. Normal serum enzyme levels do not exclude steatosis of the liver.

Evaluation of the pathogenesis of flatulence and abdominal cramps in patients with lactose malabsorption.

Aim of this study was to assess whether the interindividual differences in the development of flatulence and cramps in patients with lactose malabsorption are due to the quantity of malabsorbed lactose or gas accumulation, or if accelerated intestinal transit or increased perception of gas might play a role. Hydrogen breath tests were performed in 43 patients with lactose malabsorption after ingestion of 50 g lactose and, on a separate day, 25 g lactulose. The unabsorbed amount of lactose, small bowel transit time and colonic hydrogen accumulation were assessed in patients who did and did not develop flatulence and cramps after ingestion of lactose. The unabsorbed amount of lactose, small bowel transit time and volume and rate of colonic hydrogen accumulation were the same in patients who did or did not have symptoms after lactose. Patients with flatulence and cramps had a significantly longer time interval between the onset of the increase and peak breath hydrogen concentration (p < 0.05) and a significant correlation between the time of occurrence of peak symptoms and the time of peak breath hydrogen concentration (r = 0.75, p < 0.001). Our data suggest that subjective symptoms of lactose intolerance are not due to the amount of malabsorbed lactose or to the volume or rate of gas accumulation per se, but are related to increased perception of gas.

Assessment of the influence of hydrogen nonexcretion on the usefulness of the hydrogen breath test and lactose tolerance test.

The recognition of hydrogen nonexcretion in up to 20% of tested subjects and the large ethnic differences in the prevalence of lactose malabsorption make it necessary to reassess the diagnostic usefulness of the lactose tolerance test and the hydrogen breath test. Both tests were performed in 83 consecutive patients with suspected lactose malabsorption who ingested 50 g lactose. On a separate day a hydrogen breath test was performed after 25 g lactulose. The prevalence of hydrogen nonexcretion was 18%. The diagnostic usefulness of hydrogen breath test was influenced both by the individual threshold for hydrogen excretion and the amount of malabsorbed lactose. In addition to baseline values, breath samples for hydrogen measurements have to be taken at 30, 60, 90, 180, and 240 minutes after ingestion of lactose. For the lactose tolerance test only one measurement of serum glucose at 30 minutes is needed in addition to the baseline measurement. The combination of both tests excludes the influence of hydrogen nonexcretion, but even if a combined diagnostic approach utilizing the lactose hydrogen breath test and lactose tolerance test is used, 6% of patients presenting with symptoms suggestive of lactose intolerance cannot be classified.

[Kala-azar acquired in Croatia]. / In Kroatien erworbene Kala-Azar.

Six weeks after his return from a two-week vacation in Croatia a 52 year-old janitor from Graz complained of loss of appetite, fever, headache, and a 9-kg weight loss. The spleen was enlarged to 16cm as measured by sonography. Laboratory tests revealed pancytopenia, a prolonged prothrombin time and elevation of serum LDH concentration. While repeated bone marrow biopsy showed no signs of leishmaniasis, high antibody titers against leishmania antigen led to the diagnosis of kala-azar. The indirect immunofluorescent antibody test (1:128) and a haemagglutination-inhibition test (1:512) showed diagnostic elevations of titers. Therapy with pentostam led to prompt defervescence and resulted in a full recovery of the patient. After six weeks a marked decrease of antibody titers in the haemagglutination-inhibition test (1:16) could be observed. Leishmaniasis has to be considered in patients with fever of unknown origin who return from Mediterranean countries. Despite a negative bone marrow biopsy a diagnosis is possible on the basis of serological tests. This is important because effective therapy is available as illustrated by this patient and because of the fact that the disease runs a lethal course if the diagnosis is missed.