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.

[Working hours and job satisfaction among physicians in hospitals and general practice in Munich. Results of an anonymous questionnaire]. / Arbeitszeit und Arbeitszufriedenheit angestellter und beamteter Arzte in München. Ergebnisse einer anonymen Befragung.

PURPOSE: In autumn 2004 the local association of physicians (Arztlicher Kreis- und Bezirksverband München) performed a survey among employed physicians in Munich on working hours and working conditions. The aim of the study was to assess the extent to which the German law on working hours is actually implemented in employed physicians, and to obtain information about their work satisfaction. METHODS: A questionnaire was sent to all employed physicians in hospitals and medical practices. Participants were asked to give anonymous information and send it back per mail. RESULTS: In total, 2450 out of 5461 physicians took part in the survey. 45% reported that their working hours do not meet the German law on working hours of 1994. 44.4% stated that overtime is not fully recognized by their employers. 43.5% think the job would become more attractive if the law was implemented. 63.3% expect an income loss with the implementation. 53.7% are thinking about quitting their job. For 59.9% the burden of long working hours is an important reason for this. Women are more likely to be given a limited employment contract than men, and their overtime is more rarely recognized in full. CONCLUSION: Many employed physicians in Munich are dissatisfied with their job. The high burden of long working hours is a main reason for this.

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.

Improved antigen and nucleic acid detection in a bovine virus diarrhoea eradication program.

A bovine viral diarrhoea/mucosal disease (BVD/MD) control and eradication program was introduced in Lower Austria in 1996, according to the Swedish model. An important risk factor for BVD transmission under local conditions is communal grazing where susceptible pregnant cattle from several herds may be mixed with unrecognised persistently infected (PI) animals. A reliable system for identification of PI animals is therefore essential for BVD eradication and steps were taken to improve a commercially available antigen-capture ELISA (Ag-ELISA) by modifying the method for leukocyte preparation and adjusting the negative cut-off value. A single-tube reverse transcriptase-polymerase chain reaction (RT-PCR) employing panpestivirus 324/326 primers targeting the 5'-untranslated region of the virus genome was also simplified and used on pooled blood samples to facilitate larger sample throughputs. RT-PCR positive pools were analysed individually to identify infected animals. Seven hundred eighty-six samples were tested by Ag-ELISA according to the instruction manual and 5324 samples with the modified method. All 6110 samples were retested by RT-PCR. The percentage of RT-PCR positive results with doubtful and negative Ag-ELISA samples significantly diminished using the modified method (from 4.71 to 0.82%). Selected BVD viruses were genetically typed by PCR product sequencing; special attention being paid to RT-PCR amplicons from samples which were negative or doubtful by ELISA. However, no correlation was found between the phylogenetic grouping of the viruses and the Ag-ELISA results.

[Effect of cisapride on clearance of gallstone fragments after extracorporeal shockwave lithotripsy of gallstones]. / Einfluss von Cisapride auf die Clearance von Steinfragmenten nach extrakorporaler Stosswellenlithotripsie (ESWL) von Gallensteinen.

Stone fragments remaining in the gallbladder are an important problem after ESWL. Cisapride (CIS) improves gallbladder contraction and hence we decided to investigate whether clearance of stone fragments after ESWL for radiolucent gallbladder stones can be increased by cisapride. Six to 15 months (median 12) after ESWL 48 patients with remaining gallstone fragments of less than 5 mm in diameter were randomized either to Group A, who received cisapride 10 mg t.i.d. orally for 3 months in addition to oral litholysis (OLL) with ursodeoxycholic acid 500 mg/day and chenodeoxycholic acid 500 mg/day, or to Group B, who continued solely with OLL. All patients had started OLL within the fortnight-preceding ESWL. Gallbladder contractility, as measured by oral cholecystography with a fatty meal, was intact in all patients prior to ESWL. Maximal diameter and number of fragments were assessed by ultrasound (5 mHz) in different positions of the patient at the beginning of the study and after 3 months. Total clearance of fragments, which includes clearance of all sludge, occurred in only 3 patients, two of whom received only OLL. After 3 months the number of fragments decreased in 6 patients in Group A and in 7 patients in Group B. Three patients stopped taking cisapride before completion of the study, two because of diarrhoea, and one because of dysuria. All symptoms were readily reversible after discontinuing cisapride. In conclusion, cisapride combined with OLL does not enhance clearance of the gallbladder when fragments are still present one year after ESWL.

[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.

[So-called nephrogenic adenoma (adenomatous metaplasia). A rare tumorous adenopapillary lesion of the urothelium in the urinary bladder in a 6-year-old boy following injury]. / Sogenanntes nephrogenes Adenom (adenomatöse Metaplasie). Seltene tumorartige adenopapilläre Läsion des Urothels in der Harnblase bei einem 6-jährigen Knaben nach Trauma.

A 6-year-old boy developed an extensive adenopapillary proliferation of the urothelium of the urinary bladder--a nephrogenic adenoma (adenomatous metaplasia)--2 years after he had been injured in an accident, which was followed by operation and medical treatment. Histologically this lesion is characteristic. Like other epithelial tumors of the urinary tract, it is very rarely found in children. A dysontogenetic or metaplastic pathogenesis has been suggested. Once more is known about them, adenomas may be diagnosed more often. The clinical picture and therapy are briefly discussed and a review of the literature is given.

Incidence of inflammatory bowel disease in the province of Styria, Austria, from 1997 to 2007: a population-based study.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) varies widely between different countries. This large variation is also observed for the incidence of its main two forms, ulcerative colitis (UC) and Crohn's disease (CD). Controversy exists whether IBD incidence is increasing, especially in western countries. Currently no data are available for Austria. This study therefore aimed to evaluate for the first time the incidence of IBD over an eleven-year period in Styria, a province of Austria with a population of 1.2 million. METHODS: All patients with an initial diagnosis of IBD between 1997 and 2007, who were Styrian residents, were eligible for this retrospective study. Data were acquired from electronically stored hospital discharge reports and individual reports by patients and physicians. According to population density Styria was divided into two rural and one urban area. RESULTS: Throughout the study period 1527 patients with an initial diagnosis of IBD were identified. The average annual incidence was 6.7 (95% CI 6.2-7.1) per 100,000 persons per year for CD and 4.8 (95% CI 4.5-5.2) for UC. The average annual incidence increased significantly (p<0.01) for both diseases during the 11 year study period. Median age at initial diagnosis was 29 years (range 3-87) for CD and 39 years (range 3-94) for UC. At diagnosis, 8.5% of all IBD patients were <18 years of age. The incidence of both CD and UC was significantly higher in the urban area than in rural areas (CD: 8.8, 95% CI 7.8-9.8 versus 5.5, 95% CI 4.7-6.4 and 5.9, 95% CI 5.3-6.7; [p<0.001]; UC: 5.8, 95% CI 5.1-6.6 versus 4.0, 95% CI 3.4-4.7 and 4.7, 95% CI 4.1-5.4; [p=0.04]). CONCLUSION: We observed an overall increase in the incidence of ulcerative colitis and Crohn's disease in a part of Austria during an eleven year period. IBD was more predominant in the largest urban area than in rural areas.

A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease.

Infliximab (IFX) has tremendously enriched the therapy of inflammatory bowel diseases (IBD) and other immune mediated diseases. Although the efficacy of IFX was undoubtedly proven during the last decade numerous publications have also caused various safety concerns. To summarize the immense information concerning adverse events and safety issues the Austrian Society of Gastroenterology and Hepatology launched this evidence based consensus on the safe use of IFX which covers the following topics: infusion reactions and immunogenicity, skin reactions, opportunistic infections (including tuberculosis), non-opportunistic infections (bacterial and viral), vaccination, neurological complications, hepatotoxicity, congestive heart failure, haematological side effects, intestinal strictures, stenosis and bowel obstruction (SSO), concomitant medication, malignancy and lymphoma, IFX in the elderly and the young, mortality, fertility, pregnancy and breast feeding. To make the vast amount of information practicable for routine application the consensus was finally condensed into a checklist for a safe use of IFX which consists of two parts: issues to be addressed prior to anti-TNF therapy and issues to be addressed during maintenance. Both parts are further divided into obligatory and facultative items.

[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]. / Aminosalicylate und Steroide in der Behandlung von chronisch entzündlichen Darmerkrankungen -- Konsensuspapier der Arbeitsgruppe für chronisch entzündliche Darmerkrankungen der 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.

Special experiments on central nervous effects of amitriptylinoxide considering pharmacokinetic aspects.

A few conclusive experimental models (barbiturate sleep, tetrabenazine reversion, maximum electroshock) were chosen to collect comprehensive data on the pharmacodynamic characteristics of amitriptylinoxide. The following results appear to be of particular importance: 1. The drive-promoting effect of amitriptylinxide increases with repeated application of the substance. Its maximum level is reached after approx. 5 to 10 days. A simultaneous decrease of the sedative component is observed during the same interval. These processes can be explained neither by accumulation nor by developing of drug tolerance but have to be attributed to a change in metabolic processes. 2. Comparative investigations of oral and i.v. application led to the conclusion that amitriptylinoxide is absorbed rapidly and almost completely from the intestine when administered orally. Maximum action is demonstrable at about 1 h after oral administration. 3. As had been expected, diazepam intensified the sedative effect of amitriptylinoxide. The findings obtained suggest an additive action of the two substances.

[Biodynamics of the hip joint. The elasticity of the human femur and its importance]. / Zur Biodynamik des Hüftgelenkes Das Federverhalten des menschlichen Femur und seine Bedeutung

Pauwels' biomechanical analysis of hip joint function shows that the dynamic forces acting on the joint can be large. In these techniques, spring mechanisms are being used to neutralize dynamic forces. The question remains as to whether such a mechanism in humans exists in the vicinity of the hip joint, i.e. in the femur. Fresh human femoral bones were put under axial stress and their qualities examined. Different spring qualities were found in the various femora; and by comparing these, 6 groups were established which were then subjected to statistical analysis. More than half the bones examined possessed good spring qualities. A practical example proves that the spring qualities of the femur are apt to absorb a considerable amount of kinetic energy during the axial stress and thus lessen the vertical mechanical strain vector of the hip joint.

[Traumatic cartilage damage of the knee joint]. / Der traumatische Knorpelschaden am Kniegelenk.

Thirty-five traumatic lesions to cartilage were recorded, together with other injuries, from 225 arthroscopic examinations in two years. Most of the lesions (20) were located at the femoral condyle. The patella was involved in eight cases. However, if the patellar surface was related to the surface of the femoral condyles, the former was just as strongly affected by traumatic effects as the latter. No unambiguous localisation was possible in six cases, most of them smaller cartilage abrasions. Optional therapy proved to be applicable via the arthroscope in seven cases, while small incisions in the form of mini-arthrotomy were necessary in five cases. Arthrotomy was performed on 21 patients, and no therapeutic action at all was required in two cases. Complications included one transient soft-tissue infection and haemarthrosis of one patients who had to be punctured. Following very short-time immobilisation in plaster cast, the use of forearm walking supports was considered appropriate for short-term weight relief. A weight-relieving orthotic device with dynamic partial-loading facility was fitted for longer-term weight relief.

[Cruciate ligament injuries. Results of a follow-up study]. / Kreuzband-Verletzungen. Ergebnisse einer Nachuntersuchung.

The paper describes the long term results of 48 patients treated operatively or conservatively because of injury to the cruciate ligaments. The first part deals with the main problems in treating these damages. The second part draws up the extent, age and cause of the injury in these 48 patients. 21 patients (with 22 damages to the cruciate ligaments) underwent clinical and radiological follow-up examination. There were 1 very good, 4 good, 11 fair, and 6 bad results. The results felt subjectively by the patients were: 5 very good, 6 good, 8 fair, and 3 bad.

Central nervous effects of a new tricyclic antidepressant (amitriptylinoxide).

The central action of amitriptylinoxide was investigated in mice and rats using established models. The substance was found to possess antidepressant, drive-promoting properties which correspond to amitriptyline in their intensity or are superior even. In addition the pharmacodynamic spectrum of amitriptylinoxide displays a sedative component that is considered a desirable accompanying effect but is somewhat weaker than with amitriptyline. According to revealed differences in this work between the pharmacological activities of amitripytlinoxide and those of other tricyclic antidepressants, it became reasonable to undertake further studies to investigate its main and side effects.

Charge-transfer interactions between metal ions and some uracil derivatives.

The interaction between Cu2+ and a few uracil derivatives has been investigated by means of electron spin resonance and optical absorption studies. It could be shown that a charge transfer interaction occurs. Its strength depends upon the electron attracting or releasing properties of the substitutents of the nucleobase.