[Musculoskeletal disorders among urologists-is there an association with open pelvic surgery? : Results of a national survey]. / Muskuloskelettale Erkrankungen bei Operateuren in der Urologie ­ besteht ein Zusammenhang mit der offenen Beckenchirurgie? : Ergebnisse einer nationalen Erhebung.

BACKGROUND: In urology, the health implications of open pelvic surgery (OPS) on the patient have been the subject of numerous studies. However, health effects on the surgeon have not yet been sufficiently considered. The present study investigates the relationship between musculoskeletal disorders in urological surgeons and their activity in OPS. MATERIALS AND METHODS: From the point of view of occupational physiology, exemplary operations in OPS were examined using the key indicator method (KIM). In addition, a web-based survey among German clinicians was carried out. From the collected variables, models for the prediction of the endpoints pain and disc herniation (DH) were generated by multivariate logistic regression. RESULTS: Risk assessment of the operations with KIM could show that OPS presents a significantly increased physical workload and thus potential physical overstraining. Of the 605 participants in the survey, 35.4% were urologists performing OPS, 32.0% were urologists not performing OPS and 32.6% were gastroenterologists (control groups). Activity in OPS had an odds ratio (OR) of 1.09 (confidence interval [CI]: 0.72-1.66, p = 0.69) for predicting pain, and an OR of 1.14 for prediction of DH CI: 0.66-1.94; p = 0.64). Statistically significant factors influencing the perception of pain were BMI, gender and work ability index (WAI), whereas age and WAI were significant for the occurrence of DH. CONCLUSION: Our survey could not show that surgeons practicing OPS have a significantly increased rate of musculoskeletal disorders or, in particular, an increased rate of DH in comparison to the control groups. Nevertheless, the rate of reported complaints among all clinicians surveyed is high, and the random risk assessment of the examplary OPS operations could also demonstrate the risk of physical overstraining. Further considerations should therefore be made as to how reduce the strain on the musculoskeletal system.

ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study.

BACKGROUND: Non-adherence to medication is a challenging problem in daily clinical practice. OBJECTIVE: To assess reasons for non-adherence in patients with chronic immune-mediated inflammatory diseases (IMIDs) in a direct comparison including evaluation of treatment necessity and concerns. METHODS: ALIGN was a non-interventional, multicountry, multicentre, self-administered, cross-sectional, epidemiologic survey study. Here, we investigate the German, Austrian and Swiss (DACH) cohort. Six hundred thirty-one patients with different IMIDs (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ulcerative colitis) under systemic therapies were evaluated concerning adherence, beliefs of necessity and concerns towards treatment in patients with IMIDs. RESULTS: The DACH cohort had significantly different levels of adherence depending on the IMID (P < 0.05) and the type of therapy (P < 0.05). Based on the significant influence of concerns on treatment adherence (P < 0.05) and the high belief of treatment necessity, patients could be classified in four attitudinal segments, which were unequally distributed throughout various IMIDs. High concerns had a significant influence on non-adherence, whereas necessity did not. Older age, female sex, TNFi mono-, conventional combination and TNFi combination therapy are positively associated with adherence. CONCLUSIONS: In the DACH region, patients are less concerned about medication and believe in the necessity of treatment. Therefore, we suggest adapting the communication in the various patient groups.

[The enteric glia--part of the puzzle in Crohn's disease?]. / Die enterische Glia--Ein Teil des Crohn Puzzles?

Enteric glia cells are essential for the mucosal integrity of the gut. A leakage of the epithelial barrier is postulated in Crohn's disease. The role of enteric glia cells in the onset and progress of Crohn's disease is not clear yet. A new approach in the therapy of Crohn's disease is to target "mucosal healing". Since enteric glia cells are an important source of factors that regulate the epithelial barrier function, further research and discussion about this cell entity under therapeutic aspects is urgently necessary.

A single dose of intravenous zoledronate prevents glucocorticoid therapy-associated bone loss in acute flare of Crohn's disease, a randomized controlled trial.

OBJECTIVES: To assess the effectiveness and safety of zoledronate (ZOL) in preventing glucocorticoid therapy-associated bone loss in patients with acute flare of Crohn's disease (CD) in a randomized, double-blind, placebo-controlled trial. METHODS: Forty CD patients starting a glucocorticoid therapy (60 mg prednisolone per day) for acute flare (CD activity index (CDAI) >220) were randomized to compare the effect of ZOL (4 mg intravenous, n=20) or placebo (n=20) on change in lumbar bone mineral density (BMD). All patients received calcium citrate (800 mg) and colecalciferol (1,000 IU) daily. Dual energy X-ray absorptiometry (DXA) of the lumbar spine (L1-L4) was performed at baseline and day 90. Follow-up examinations at day 1/7/14/30 and 90 included laboratory tests and adverse event/serious adverse events reports. RESULTS: Thirty-six patients were available for per-protocol analysis. With placebo (n=18), a decrease in BMD was seen (T-score: -0.98 ± 0.8, day 0 and -1.25 ± 0.77, day 90, P=0.06), with ZOL (n=18) BMD increased (-1.15 ± 1.02, day 0 and -0.74 ± 1.09, day 90, P=0.03). The change in BMD under placebo (-0.26 ± 0.21) vs. ZOL (+0.41 ± 0.19) was highly significant (P=0.006). In all, 14 out of 18 patients with ZOL had an increase in BMD (+0.64 ± 0.48), 12 of 18 with placebo a decrease (-0.50 ± 0.39). Changes of clinical findings and laboratory results of inflammation (leukocytes, platelets, and C-reactive protein) were the same in- and between-groups throughout the study. With ZOL, serum bone degradation marker ß-Cross-Laps decreased. Study medication was safe and well tolerated. CONCLUSIONS: ZOL is effective in preventing glucocorticoid therapy-induced bone loss in patients with acute flare of CD and should be considered whenever a glucocorticoid therapy is started in CD patients.

Bones and Crohn's: estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density.

BACKGROUND: Reduced bone mineral density (BMD) and osteoporosis are frequent in Crohn's disease (CD), but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2), is an established risk factor in postmenopausal osteoporosis. AIM: To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. METHODS: 111 male CD patients underwent osteodensitometry (DXA) of the spine (L1-L4). Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI). Testosterone (T), dihydrotestosterone (DHT), estradiol (E2), sex hormone binding globulin (SHBG), Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP) were measured in 111 patients and 99 age-matched controls. RESULTS: Patients had lower T, E2 and SHBG serum levels (p < 0.001) compared to age-matched controls. E2 deficiency was seen in 30 (27.0%) and T deficiency in 3 (2.7%) patients but only in 5 (5.1%) and 1 (1%) controls. Patients with E2 deficiency had significantly decreased T and DHT serum levels. Use of corticosteroids for 3 of 12 months was associated with lower E2 levels (p < 0.05). Patients with life-time steroids >10 g had lower BMD. 32 (28.8%) patients showed osteoporosis, 55 (49.5%) osteopenia and 24 (21.6%) had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p < 0.001), and patients with osteoporosis had higher ICTP levels than those with normal BMD. CONCLUSION: We found an altered hormonal status--i.e. E2 and, to a lesser extent T deficiency--in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.

Nerve growth factor secretion in cultured enteric glia cells is modulated by proinflammatory cytokines.

The enteric nervous system is composed of neurones and glial cells. These enteric glia cells (EGC) appear to be essential for the maintenance of gut homeostasis and mucosal integrity. Neurotrophin nerve growth factor (NGF) also plays an important role for the gut integrity by regulating sensory and inflammatory processes in the intestines. Here, we demonstrate EGCs as one source of NGF and show increased levels of NGF mRNA/protein and tropomyosin receptor kinase A (TrkA) mRNA in cultured EGCs upon stimulation with proinflammatory cytokines and lipopolysaccharides. NGF is continuously secreted from cultured EGCs and proinflammatory cytokines and lipopolysaccharides stimulate the secretion of this neurotrophin in a time- and dose- dependent manner, whereas interleukin-4 had no effect on NGF expression. Furthermore, NGF secretion was sustained for more than 12 h after withdrawal of the proinflammatory cytokines, suggesting the involvement of transcriptional and/or translational processes. Thus, the release of proinflammatory cytokines can increase NGF secretion by EGCs and leads to a higher expression of TrkA in EGCs. NGF, in turn, can increase visceral sensitivity and, on the other hand, appears to improve gut inflammation. Therefore, NGF secreting EGCs may play a key role in modulating visceral sensitivity and might be involved in inflammatory processes of the gut.

Lack of correlation between the vitamin D receptor Fokl start codon polymorphism and bone mineral density in patients with Crohn's disease.

INTRODUCTION: We have examined the association of bone mineral density of patients with inflammatory bowel disease with a polymorphism in the gene encoding the vitamin D receptor. The thymine/cytosine (T/C) polymorphism in the first of two start codons can be defined by a restriction fragment length polymorphism using the restriction endonuclease FokI. Vitamin D receptor alleles containing the polymorphism have been denoted by f and alleles lacking the site by F. METHODS: We report on an association analysis of a basic population of 244 caucasian patients with Crohn's disease. We have genotyped the FokI polymorphism of the VDR in these patients and associated the genotype with the bone mineral density of the lumbar spine and the femoral neck. RESULTS: In the cohort 42% of the patients were scored FF homozygous, 43.7% Ff heterozygous, and 14.3% ff homozygous. 14.4% of the FF patients, 18.8% of the Ff patients, and 9.7% of the ff patients had osteoporosis of the lumbar spine and 21.25% of the FF patients, 25.3% of the Ff patients, and 18.5% of the ff patients had osteoporosis of the femoral neck. In this cohort no association between the genotype and the bone mineral density in the group as a whole nor when separated according to sex or age was found. CONCLUSIONS: In summary in our cohort no association of the FokI polymorphism and the BMD of the lumbar spine and femoral neck in patients with inflammatory bowel disease was found.

[Intestinal wall vascularisation in Crohn's disease]. / Darmwandvaskularisation bei Morbus Crohn.

BACKGROUND AND AIMS: In a pilot study the semi-quantitative classification of intestinal wall vascularisation as proposed by Limberg was evaluated. PATIENTS AND METHODS: 20 patients with confirmed Crohn's disease and clinical activity (10 male, 10 female, mean age 30.0 +/- 7.72 years, range 21 - 49 years, mean time since onset of disease 4.6 years, range 0 - 15 years) were included. CDAI, CRP, ESR, and the blood count were evaluated. Two and six weeks after inclusion into the study these examinations were repeated. All patients were treated with anti-inflammatory drugs. The intestinal wall thickness was measured with ultrasound. The vascularisation following the Limberg classification and the number of blood vessels per square centimetre were assessed in the power-Doppler mode. RESULTS: The mean length of bowel segments with increased wall thickness (> 3 mm) at the beginning of the study was 20.3 cm (range 5 - 50 cm), the mean intestinal wall diameter 5.9 mm (range 4 - 9 mm). The mean density of blood vessels in the power-Doppler mode was 3.8 vessels/cm (2) (range 0 - 8 vessels/cm (2)), the median of Limberg levels was 2 (range 1 - 4). The density of blood vessels per cm (2) well correlated with the Limberg classification throughout the study (r = 0.2 at start; r = 0.94 at 1st follow-up; r = 0.91 at 2nd follow-up). CONCLUSION: The classification for measuring intestinal wall vascularisation semi-quantitatively (as proposed by Limberg) proved to be easily applicable in routine sonography. Besides the measurement of intestinal wall thickness, activity indices, clinical and laboratory parameters, it may constitute an additional means for evaluation of disease activity.

Thioguanine-nucleotides do not predict efficacy of tioguanine in Crohn's disease.

BACKGROUND: 6-Thioguanine-nucleotides seem to be the active metabolites of thiopurine therapy, and their monitoring has been considered a useful tool for optimizing response in inflammatory bowel diseases. Tioguanine (thioguanine) therapy results in much higher levels of 6-thioguanine-nucleotide levels when compared with azathioprine or mercaptopurine. AIM: To elucidate the influence of 6-thioguanine-nucleotide and methylated 6-thioguanine-nucleotide levels under tioguanine on efficacy and toxicity in Crohn's disease. METHODS: 6-Thioguanine-nucleotide and methylated 6-tioguanine-nucleotide levels were measured regularly in 26 Crohn's disease patients treated with tioguanine. Nucleotide levels were related to efficacy and toxicity. RESULTS: 6-Thioguanine-nucleotide levels rose very high [median 1241 pmol/8 x 10(8) red blood cells (range 313-1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 x 10(8) red blood cells (154-1775)]. 6-Thioguanine-nucleotide and methylated 6-thioguanine-nucleotide concentrations correlated significantly (r = 0.7, P < 0.0001). Nucleotide levels from patients achieving remission (n = 14) did not differ significantly from non-remitters (n = 12) [6-thioguanine-nucleotide: 1077 (599-2160) vs. 1210 (534-4665); methylated 6-thioguanine-nucleotide: 510 (214-1222) vs. 421 (145-1284)]. One patient with intermediate thiopurine S-methyltransferase activity experienced bone marrow toxicity upon dose escalation parallel with excessively high thioguanine-nucleotide levels. CONCLUSIONS: 6-Thioguanine-nucleotide as well as methylated 6-thioguanine-nucleotide levels under tioguanine therapy were not related to efficacy. This suggests that monitoring of 6-thioguanine-nucleotide levels is not a useful tool to predict response to thiopurines.

Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia.

BACKGROUND: Enteric glia protect the integrity of the gut, as loss of enteric glial fibrillary acidic protein (GFAP) positive (+) glia leads to a haemorrhagic jejunoileitis. Crohn's disease (CD) and necrotising enterocolitis (NEC) show pathological changes in enteric glia. Therefore, factors controlling GFAP+ enteric glia are of great interest. The aim of the present study was to characterise enteric glia and determine the effect of interleukin 1beta (IL-1beta), interleukin 4 (IL-4), tumour necrosis factor alpha (TNF-alpha), and lipopolysaccharides (LPS) on cultured enteric glia. METHODS: Dissected rat colon and cultured enteric glia cells were double labelled with anti-GFAP and anti-S-100 antibodies. For regulatory studies, enteric glia cells were treated with cytokines and LPS. Proliferation was assayed using bromodeoxyuridine (BrdU) and mitosis of enteric glia was blocked by demecolcine. RESULTS: We were able to distinguish GFAP negative (-) from GFAP+ glia subtypes in situ and in primary cultures. Incubation of cells with IL-1beta, TNF-alpha, and LPS led to a significant increase in GFAP+ enteric glia while IL-4 had no effect on GFAP expression. After incubation with IL-1beta, total intracellular GFAP of enteric glia cells was increased. Upregulation of GFAP+ enteric glia could also be observed after stimulation with IL-1beta on blocking mitosis. BrdU uptake in stimulated enteric glia showed no increased proliferation rate. CONCLUSIONS: Two different types of enteric glia based on GFAP expression exist in the gut. Proinflammatory cytokines and LPS cause a dramatic increase in GFAP+ enteric glia. This suggests that cytokines play an important role in controlling GFAP+ enteric glia which might in turn be involved in modulating the integrity of the bowel during inflammation.

Diagnosis and management of osteoporosis in inflammatory bowel disease.

Osteoporosis is a frequent finding in patients with Crohn's disease and ulcerative colitis. The prevalence of vertebral fractures in those patients with significantly reduced bone mineral density is up to 22%. Factors contributing to osteoporosis in inflammatory bowel disease (IBD) patients are treatment with glucocorticoids, increased cytokine production by the inflammation itself, malabsorption and possibly hypogonadism. Therefore, consequent treatment of the underlying IBD and minimising therapy with systemic glucocorticoids, as well as the adequate intake of calcium and vitamin D, may be very important measures to prevent bone loss in IBD. In patients with osteoporosis associated with Crohn's disease or ulcerative colitis, various treatment strategies, such as sodium fluoride and aminobisphosphonates, are discussed. Unfortunately, interventional studies in secondary osteoporosis are often limited by the small study population. The efficacy in prevention of vertebral fractures is not proven in any of the described treatment modalities in these patients. Therefore, guidelines are based on data using bone density as the most accepted surrogate marker and treatment guidelines are based on data from patients with postmenopausal and steroid-induced osteoporosis.

[Osteoporosis in inflammatory bowel disease - results of a survey among members of the German Crohn's and Ulcerative Colitis Association]. / Osteoporose bei chronisch entzündlichen Darmerkrankungen - Ergebnisse einer Umfrage an Mitgliedern der Deutschen M. Crohn und Colitis ulcerosa Vereinigung (DCCV).

INTRODUCTION: Osteoporosis is a frequent and clinically important complication in inflammatory bowel disease (IBD). Prevalence and risk factors have been examined in small numbers of patients. With a nationwide survey of members of the German Crohn's and Ulcerative Colitis Association (DCCV) we wanted to evaluate the situation in a larger group of patients. METHODS: Questionnaires were sent with the autumn issue of the members journal to approx. 14,620 affected members of the DCCV. Items covered osteoporosis, clinical symptoms, anamnesis and sociodemographic topics. Results are presented as descriptive analysis and in a logistic regression analysis of factors contributing to the osteoporosis risk. RESULTS: 2,536 questionnaires could be used (17.3 %). Mean age and distribution concerning diagnosis and gender were comparable to the DCCV members in total. The prevalence of pathologic bone density was 62.3 % in those 1,265 patients (50.1 %) who underwent bone densitometry in the course of their disease. The analysis led to the following possible risk factors: disease activity (high chronic activity or more than 1 acute flare annually vs. remission, p < 0.001), lifetime steroid dosage > 10 g (p = 0.002), Crohn's disease vs. ulcerative colitis (p = 0.02), multiple bowel resection (p = 0.032), age (p = 0.018) and low body mass index (p = 0.034). 83.4 % of the patients with pathologic bone density received specific therapy, but most of those (63.5 %) were solely substituted with calcium and vitamin D. CONCLUSION: This is the first study looking at epidemiology and risk factors of osteoporosis in a large study population of patients with inflammatory bowel disease. Although the prevalence may be overestimated due to selection bias in our study, osteoporosis is confirmed as a frequent and clinically relevant complication in IBD. Bone densitometry is recommended in those patients with one or more risk factors.

[Comparison of conventional enteroclysis, intestinal ultrasound and MRI-enteroclysis for determining changes in the small intestine and complications in patients with Crohn's disease]. / Vergleich von Darmwandsonographie, Enteroklysma und Magnetresonanztomographie in der Erkennung von Darmwandveränderungen und Komplikationen im Dünndarm bei Patienten mit M. Crohn.

BACKGROUND: Enteroclysis, intestinal wall ultrasound (IWU) and abdominal magnetic resonance imaging (MRI) are three established methods in the diagnosis of Crohn's disease (CD). To date, however, the three methods have not been compared in one patient collective. AIMS: The present prospective study compared the relative performance of IWU, MRI and enteroclysis in determining the extent of disease involvement and intestinal complications in patients with CD both at initial diagnosis and during follow-up. PATIENTS AND METHODS: Included in the present study were 48 patients with confirmed CD (age: 19-66 years) examined with all three methods between August 1999 and December 2000. IWU was performed in B-mode with a 4-7 MHz convex transducer head and a 5-12 MHz linear transducer head by an experienced examiner. At MRI, T1 and T2 weighted sequenced (Flash 2D before and after intravenous application of gadolinium DTPA or TSE) were acquired in coronal and transverse planes. Enteroclysis was performed using conventional biphasic technique. Interpretation was conducted on the basis of a standardized catalogue of findings. RESULTS: Changes in bowel segments consistent with inflammation were identified in 41 of 48 patients. All three methods returned equivalent findings with regard to the length of inflamed bowel segments (IWU, range: 3-25 cm, mean: 12 cm; MRI, range: 3-25 cm, mean: 10 cm; enteroclysis, range: 3-30 cm, mean: 11 cm) and wall thickness (IWU, range: 4-10 mm, mean: 7 mm; MRI, range: 5-10 mm, mean: 7 mm; of nine patients with stenotic change, five were correctly diagnosed with IWU (sensitivity, 55.6%; specificity, 97.4%), four with MRI (sensitivity, 44.4%; specificity, 100%) and six with enteroclysis (sensitivity, 66.7%; specificity, 100%). Fistulae were correctly identified in five patients with IWU (sensitivity, 55.6%; specificity, 97.4%), in four with MRI (sensitivity, 44.4%; specificity, 100%) and in six with enteroclysis (sensitivity, 66.7%; specificity, 100 %) of a total of nine patients with confirmed fistula formation. Abscesses were correctly identified in five patients with IWU (specificity, 66.7%; specificity, 100%), in five with MRI (sensitivity, 83.3%; specificity, 100%) and in no patients with enteroclysis (sensitivity, 0%; specificity, 100%) in six patients with abscesses. CONCLUSION: Both IWU and MRI identify extent, severity and intestinal complications with adequate diagnostic accuracy in patients with CD. Both techniques possess the potential for replacing enteroclysis in the work-up of CD. Enteroclysis should be reserved for the work-up of complex fistula systems.