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M Reinshagen

Publications and source records attributed to M Reinshagen.

At least 19 recordsLinked to original sources
PubMed2006

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.

Bone Density↗
PubMed2006

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.

Animals↗
PubMed2004

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.

Adult↗
PubMed2004

[Intestinal wall vascularisation in Crohn's disease].

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.

Adult↗
PubMed2004

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.

Animals↗
PubMed2004

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.

Bone Density↗
PubMed2003

Therapy of osteoporosis in patients with Crohn's disease: a randomized study comparing sodium fluoride and ibandronate.

BACKGROUND: Osteoporosis is a frequent complication in Crohn's disease. Although the efficacy of both sodium fluoride and aminobisphosphonates in postmenopausal osteoporosis has been investigated in long-term therapy studies, no long-term results are available regarding the effect of these agents in the management of osteoporosis in patients with Crohn's disease. METHODS: Eighty-four patients with Crohn's disease and pathological bone mineral density findings were randomized to receive either vitamin D3 (1000 IU) and calcium citrate (800 mg) daily (group A) or sodium fluoride (25 mg b.d., group B) or intravenous ibandronate (1 mg every 3 months, group C) in addition to daily calcium/vitamin D substitution. On admission to the study and after 12 and 27 months, patients underwent dual-energy X-ray absorptiometry and radiological examination of the spine. RESULTS: Sixty-eight patients completed the 1-year observation period and were available for the intention-to-treat analysis. No new vertebral fractures were diagnosed. In group A, lumbar bone density increased by 2.6% (P = 0.066, N.S.), in group B by 5.7% (P = 0.003) and in group C by 5.4% (P = 0.003). Therapy with sodium fluoride was associated with an increase in osteocalcin (N.S.), whereas administration of ibandronate was associated with a decrease in the resorption parameter, carboxy-terminal cross-linked type-I collagen telopeptide (P < 0.05). Both sodium fluoride and ibandronate resulted in significant decreases in the serum concentration of osteoprotegerin after 9 months (P < 0.001). CONCLUSIONS: The findings of the present study show that both sodium fluoride and ibandronate are effective in combination with calcium and vitamin D substitution in the management of osteopenia and osteoporosis in patients with Crohn's disease. Both agents are safe and well tolerated, and induce continuous increases in lumbar bone density.

Bone Density↗
PubMed2003

6-thioguanine--efficacy and safety in chronic active Crohn's disease.

BACKGROUND: : Azathioprine and mercaptopurine are commonly used in chronic active Crohn's disease. They share the disadvantage of a delayed onset of action and potentially serious side-effects, and are metabolized to thioguanine nucleotides which are thought to be the active metabolites. The direct use of 6-thioguanine may offer a more rapid and safer alternative. We conducted an open prospective study to investigate the efficacy and safety of 6-thioguanine in chronic active Crohn's disease. METHODS: : Thirty-seven patients with chronic active Crohn's disease and a Crohn's disease activity index of > 150 were enrolled in this study. Inclusion criteria were steroid dependence (n = 19), steroid refractoriness (n = 9) and/or intolerance (n = 16) or refractoriness (n = 6) to azathioprine. Patients were treated with 40 mg/day of 6-thioguanine for 24 weeks; a dose escalation to 80 mg was allowed at week 12. Remission was defined as a Crohn's disease activity index of < 150 associated with a decrease of > 70 points; response was defined as a decrease of > 70 points in the Crohn's disease activity index. RESULTS: : In the intention-to-treat analysis, 13 of 37 patients achieved remission (35%). Twelve of these 13 patients achieved remission after 4 weeks. Fifty-seven per cent of patients (21/37) achieved a response. The mean Crohn's disease activity index decreased from 284 +/- 74 to 153 +/- 101. 6-Thioguanine was more effective in azathioprine-intolerant than in azathioprine-refractory patients. Twelve of 16 patients intolerant to azathioprine tolerated 6-thioguanine. Adverse events included phototoxicity, pancreatitis, headache, nausea, alopecia, arthralgia, minor infections and reversible elevation of transaminases. Six patients required discontinuation of medication, two because of leucopenia. CONCLUSIONS: : In this patient group with chronic active Crohn's disease, 6-thioguanine appeared to be effective with acceptable short-term toxicity, but long-term controlled trials are clearly needed to further define its role.

Adult↗
PubMed2003

[Comparison of conventional enteroclysis, intestinal ultrasound and MRI-enteroclysis for determining changes in the small intestine and complications in patients with Crohn's disease].

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.

Adult↗
PubMed2003

[Osteoporosis in inflammatory bowel disease - results of a survey among members of the German Crohn's and Ulcerative Colitis Association].

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.

Adolescent↗
PubMed2002

[Cost measurement based on a cost diary in patients with inflammatory bowel disease].

OBJECTIVE: Cost diaries administered by patients have been used as a method to measure costs for different diseases. Our aim was to test the application of a patient cost diary in patients with inflammatory bowel disease (IBD) and to measure disease specific resource utilization and costs. PATIENTS AND METHODS: A specific patient cost diary for IBD was developed and tested in a prospective pilot study. 105 outpatients with IBD of a University Hospital agreed to participate over a 4 week follow-up period. They were asked to report weekly their use of medical care and costs related to their illness. Visits to health care providers, hospitalizations, drug use, costs due to absence from paid and unpaid work, travel costs as well as out-of-pocket expenses were considered. RESULTS: The response rate was 90 %. Almost 70 % of the patients estimated the diary as easy to fill in. Compared with other data sources, the cost measurement using the cost diary showed good agreement regarding costs of drug therapy and outpatient hospital treatment. Mean costs due to illness were estimated to be 1,500 Euro per 4 weeks. This corresponds to total costs of about 20,000 Euro per year of care. 69 % of total costs were indirect costs due to illness-related absence from work, days of inactivity at home, and early retirement. Direct health care and direct non health care costs (e. g. travel costs) were responsible for 27 % and 4 % of costs, respectively. DISCUSSION AND CONCLUSION: The presented instrument offers a suitable and practical method of assessing IBD-related resource utilization. The prospectively obtained data for direct medical and non medical, as well as indirect costs allow a cost measurement from the societal perspective. The presented cost diary can be used for measuring costs for economic evaluations of medical interventions.

Adult↗
PubMed2002

High prevalence of osteoporotic vertebral fractures in patients with Crohn's disease.

BACKGROUND AND AIMS: Osteopenia and osteoporosis are frequent in Crohn's disease. However, there are few data on related vertebral fractures. Therefore, we evaluated prospectively the prevalence of osteoporotic vertebral fractures in these patients. METHODS: A total of 293 patients were screened with dual energy x ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur. In 156 patients with lumbar osteopenia or osteoporosis (T score <-1), x ray examinations of the thoracic and lumbar spine were performed. Assessment of fractures included visual reading of x rays and quantitative morphometry of the vertebral bodies (T4-L4), analogous to the criteria of the European Vertebral Osteoporosis Study. RESULTS: In 34 (21.8%; 18 female) of 156 Crohn's disease patients with reduced bone mineral density, 63 osteoporotic vertebral fractures (50 fx. (osteoporotic fracture with visible fracture line running into the vertebral body and/or change of outer shape) and 13 fxd. (osteoporotic fracture with change of outer shape but without visible fracture line)) were found, 50 fx. in 25 (16%, 15 female) patients and 13 fxd. in nine (5.8%, three female) patients. In four patients the fractures were clinically evident and associated with severe back pain. Approximately one third of patients with fractures were younger than 30 years. Lumbar bone mineral density was significantly reduced in patients with fractures compared with those without (T score -2.50 (0.88) v -2.07 (0.66); p<0.025) but not at the hip (-2.0 (1.1) v -1.81 (0.87); p=0.38). In subgroups analyses, no significant differences were observed. CONCLUSIONS: In patients with Crohn's disease and reduced bone mineral density, the prevalence of vertebral fractures-that is, manifest osteoporosis-was strikingly high at 22%, even in those aged less than 30 years, a problem deserving further clinical attention.

Absorptiometry, Photon↗