Biomedical subjects

A Tromm

Publications and source records attributed to A Tromm.

At least 19 recordsLinked to original sources

PubMed2004

The G2964A polymorphism of the STAT6 gene in inflammatory bowel disease.

BACKGROUND AND AIMS: Linkage of inflammatory bowel diseases to chromosome 12p13.2-q24.1 (IBD2) has been confirmed in several genome wide screens. The STAT6 gene is located within this chromosomal region. The transcription factor STAT6 is involved in the regulation of the TH1/TH2 immune response. Increased production of TH1 cytokines is crucial in the pathogenesis of Crohn's disease. PATIENTS AND METHODS: Therefore, we genotyped a single nucleotide polymorphism in the 3' untranslated region of the STAT6 gene (G2964A) in 243 patients with Crohn's disease, 100 patients with ulcerative colitis and 548 healthy controls. RESULTS: In comparison to controls, the G allele and the GG genotype frequencies were significantly increased only in Crohn's disease patients without a variation in the CARD15 gene (p<0.03 and p<0.02, respectively). CONCLUSIONS: Alterations in the STAT6 pathway may play a crucial role in the pathogenesis of distinct subgroups of patients with Crohn's disease.

Adult↗

PubMed2004

The probiotic E. coli strain Nissle 1917 for the treatment of collagenous colitis: first results of an open-label trial.

BACKGROUND: Collagenous colitis is clinically characterized by watery diarrhoea and can histologically be diagnosed by a thickening of the subepithelial collagen layer and an inflammatory infiltrate in the lamina propria. So far, the pathogenesis of collagenous colitis and the role of luminal factors remain unclear. METHODS: This clinical pilot investigation was conducted with an open-label design to monitor the clinical effects of EcN on stool frequency and stool consistency in 14 patients (11 female, 3male; age: 58.1 +/- 9.6 years). Due to the open-label protocol EcN was administered at different doses (1 - 6 capsules/day containing 2.5 - 25 x 10 (9) viable bacteria each). Except for two patients who discontinued treatment, therapy duration was at least 4 weeks. RESULTS: The results indicate a marked clinical response to the oral administration of EcN with a reduction of the stool frequency > or = 50 % in 9/14 (64 %) patients. Stool frequency clearly (p = 0.034) decreased from 7.6 +/- 4.8/day to 3.7 +/- 5.8/day at the end of therapy (between 4 and 18 weeks). Moreover, stool consistency changed in 7/14 patients from watery or slimy to soft (6 pts) and normal (1 pt), respectively. CONCLUSION: With respect to the preliminary data from this trial, the probiotic E. coli strain Nissle 1917 (EcN) seems to be of therapeutic clinical benefit in collagenous colitis. This may be explained with the recently shown antagonistic effect of EcN against Yersinia species, since a relevant number of patients suffering from collagenous colitis showed positive titres of serum IgG and IgA antibodies against Yersinia species. Further studies on the effects of EcN on mucosal collagen metabolism and long-term follow-up are warranted.

Colitis↗

PubMed2003

Interaction of polymorphisms in the CARD15 and CD14 genes in patients with Crohn disease.

BACKGROUND: Associations of variations in the CARD15 gene (Arg702Trp, Gly908Arg and Leu1007fsinsC) and Crohn disease (CD) have been shown recently. These variations are neither necessary nor sufficient for the genetic predisposition of CD. Further genetic and environmental factors play a crucial role in the pathogenesis of CD. METHODS: To evaluate putative interactions between the CARD15 and CD14 genes in CD, a functionally relevant polymorphism in the promoter region (T/C at position -159) has been genotyped for 650 healthy controls and 253 patients with CD by RFLP analyses. CD patients were genotyped for the variations of the CARD15 gene. RESULTS: T allele and TT genotype frequencies of the CD14 promoter were significantly increased only in CD patients with at least one variation in the CARD15 gene compared to controls (P = 0.02 and 0.0002, respectively). No significant association was found in CD patients without any of the variations. CONCLUSION: Interactions of the CARD15 and CD14 genes, both of which are involved in the recognition of lipopolysaccharides, increase the risk for developing CD.

Carrier Proteins↗

PubMed2002

[Peptic stenosis, motility disorder or carcinoma. What is ate the bottom of dysphagia?].

Dysphagia is the characteristic cardinal symptom of diseases of the esophagus. Etiologically, consideration must first be given to carcinoma of the esophagus. Among the cancers affecting this organ, adenocarcinoma of the distal part of the esophagus is the most common. The most important differential diagnosis in patients who have difficulty swallowing is peptic stricture of the distal esophagus arising from long-standing reflux disease. Further possible causes are motility disorders of the esophagus including, in particular, achalasia and--more rarely--diverticula, foreign bodies, membranes or rings, benign tumors or extraluminal processes.

Deglutition Disorders↗

PubMed2002

A polymorphism in the IL11 gene is associated with ulcerative colitis.

Inflammatory bowel diseases (IBD) are multifactorial disorders characterised by the host's inability to limit the inflammatory response to luminal antigens. The association of polymorphisms in the CARD15 gene with Crohn's disease (CD) demonstrates the relevance of activated transcription factor NF(kappa)B in mononuclear cells. Interleukin 11 (IL11) mediates anti-inflammatory effects and is able to downregulate LPS-induced NF(kappa)B activation. The IL11 gene is therefore a good candidate involved in genetic predisposition to IBD. To evaluate the role of the IL11 gene in IBD, two polymorphisms, including a dinucleotide repeat in the promoter region, have been genotyped in 222 patients with CD, 152 patients with ulcerative colitis (UC) and 400 healthy controls. PCR-SSCP analysis of the coding region revealed a single polymorphism in exon 4 leading to an amino acid exchange (G335A; R112H), not significantly associated with either disease. Dinucleotide repeat frequencies of the IL11.A1 allele and of IL11.A1 homozygous individuals were significantly increased among the patients with UC (P < 0.002 and (P < 0.003, respectively) but not with CD. Altered expression of IL11 appears to be involved in the genetic predisposition of UC.

Alleles↗

PubMed2002

A polymorphism in the CD14 gene is associated with Crohn disease.

BACKGROUND: Inflammatory bowel diseases (IBD) are multifactorial disorders, characterized by failure to limit the inflammatory response to luminal antigens. Although genetic factors play an important role in the pathogenesis, little is known about the genes accountable. Immune response to intestinal bacteria seems to be crucial in the pathogenesis of IBD. METHODS: To evaluate the role of the CD14 gene in IBD, a functionally relevant polymorphism in the promoter region (T/C at position -159) has been genotyped in 219 patients with Crohn disease (CD), 142 patients with ulcerative colitis (UC) and 410 healthy controls by RFLP analysis. RESULTS: T allele and TT genotype frequencies were found increased in CD patients compared to controls (Pc=0.044 and 0.005, respectively). CONCLUSION: An altered immune response to LPS seems to play a role in the genetic predisposition to CD but not to UC.

Alleles↗

PubMed2001

[Association of primary sclerosing cholangitis and sarcoidosis].

BACKGROUND: Primary sclerosing cholangitis and sarcoidosis are rarely associated diseases. CASE REPORT: We report the case of an 42-year-old woman with primary sclerosing cholangitis confirmed by endoscopic cholangiography, biopsy of the liver and serum neutrophil cytoplasmatic antibodies. Furthermore radiological and histological signs of pulmonary and hepatic manifestation of sarcoidosis were observed, besides there were alopecia areata and choledocholithiasis. CONCLUSION: The present case report gives a brief survey of the literature, reflects the theories to unknown etiology and reports actual aspects of diagnosis and therapy of both diseases.

Adult↗

PubMed2001

Interleukin-4 and interleukin-4 receptor gene polymorphisms in inflammatory bowel diseases.

Imbalances in the regulation of Th1 and Th2 lymphocytes are crucial in inflammatory bowel diseases. Interleukin-4 is secreted by Th2 lymphocytes and downregulates cytokine production from Th1 lymphocytes. Functionally relevant polymorphisms have been described in the interleukin-4 and the interleukin-4 receptor alpha genes. Association of inflammatory bowel diseases with these polymorphisms has been reported recently suggesting high transcription and enhanced signalling activity in Crohn's disease. Our study, comprising 211 patients with Crohn's disease, 147 patients with ulcerative colitis and 446 healthy controls revealed significant association of Crohn's disease with the -590 T allele of the interleukin-4 gene (P = 0.03). This allele entails reduced expression of IL-4. The reason for these contrasting findings may be discussed in the context of a putatively predisposing allele in linkage disequilibrium with the alleles of the interleukin-4 gene.

Alleles↗

PubMed2001

Cutaneous manifestations in inflammatory bowel disease.

UNLABELLED: Numerous extraintestinal manifestations in various organ systems have been reported to be associated with inflammatory bowel disease (IBD). Aim of the present paper was to evaluate the frequency of cutaneous manifestations in Crohn's disease (CD) and ulcerative colitis (UC) with respect to their location, the activity and location of the underlying disease, the treatment options and the time to remission. METHODS: The medical records of 1043 inpatients with CD and UC were screened retrospectively for extraintestinal symptoms with special regard to cutaneous manifestations. RESULTS: The prevalence of cutaneous manifestations in IBD was 22/1043 (2.1%; 18 women, 4 men; age: 31.41 +/- 9.9 [21-51] yrs.). In 15/22 patients (68.2%) the cutaneous manifestations were associated with CD, in 7/22 patients (31.8%) UC was confirmed. In 6/22 patients (27.3%) pyoderma gangrenosum (PG) was diagnosed, in 16/22 patients (72.7%) erythema nodosum (EN). EN and PG predominately occurred at the lower legs: in 68.1% the tibia was the main affection site. Other locations like breast or anus were rare. In 16/22 patients (72.7%) an acute phase of the underlying disease was evident, in 6/22 patients (27.3%) CD or UC were in remission. In patients with CD a colonic involvement was found in 86.7%. Arthritis was the most frequent coexisting extraintestinal manifestation in CD (53.3%) and UC (28.8%). Drug treatment was performed with high doses of glucocorticoids and salicylates. The time to remission in patients with EN was significantly shorter as compared to PG (5.3 +/- 1.8 vs. 19.6 +/- 14.2 weeks; p < 0.001). In 5/22 patients (22.7%) cutaneous manifestations reoccurred after a symptom-free interval. All efflorescenses reoccurred during an active phase of the underlying disease at the same manifestation site as the initial presentation. CONCLUSION: In this series the prevalence of cutaneous manifestations in IBD was 22/1043 (2.1%). EN and PG were more frequent in women with IBD, in CD, and during the acute phases of the underlying disease. EN and PG predominately affect the lower legs. Cutaneous manifestations respond well to an acute phase therapy of the underlying disease. The time to remission was significantly shorter in EN as compared to PG. However, relapses have to be considered in a relevant subgroup of patients.

Adult↗

PubMed2001

The polymorphism at position -174 of the IL-6 gene is not associated with inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel diseases (IBD) are multifactorial disorders, characterized by failure to limit the inflammatory response to luminal antigens. Genetic factors play an important role in the pathogenesis, but little is known about the accountable genes. Increased secretion of pro-inflammatory cytokines appears crucial in the initiation of the inflammatory response. METHODS: To evaluate the role of the IL-6 gene in IBD, a functionally relevant polymorphism in the promoter region (G/C at position -174) has been genotyped in 169 patients with Crohn's disease (CD), 133 patients with ulcerative colitis (UC) and 440 healthy controls by using restriction fragment length polymorphism (RFLP) analysis. RESULTS: No significant differences were apparent in the allele, genotype and carrier frequencies between patients and controls. CONCLUSION: High secretion of IL-6 does not seem to play a major role in the genetic predisposition to IBD.

Alleles↗

PubMed2001

Pharmacokinetics and rectal bioavailability of hydrocortisone acetate after single and multiple administration in healthy subjects and patients.

The pharmacokinetics and bioavailability of hydrocortisone after rectal administration of a hydrocortisone acetate foam were determined after single and multiple dosing in healthy subjects as well as in patients with inflammatory bowel disease. Endogenous hydrocortisone was suppressed by dexamethasone administration. Plasma levels were compared with those observed after intravenous administration of hydrocortisone. Only a very small part of the rectal dose (100 mg) was absorbed; the mean absolute bioavailability was 3.1% in healthy volunteers and 4.5% in patients. There was substantial intersubject variability. Although maximum hydrocortisone levels after single or multiple doses were significantly higher (about 70%) in the patient group, the systemic bioavailability is very low so that the risk of systemic side effects after rectal administration of hydrocortisone acetate foam has to be considered very low.

Administration, Rectal↗

PubMed2000

The IL-10 gene is not involved in the predisposition to inflammatory bowel disease.

Although genetic predisposition for inflammatory bowel disease (IBD) is well established, little is known about the accountable genes. The pathogenesis of IBD is characterized by an imbalanced activation of Th1- and Th2-lymphocytes. IL-10 represents an anti-inflammatory cytokine which downregulates the production of Th1-derived cytokines. To evaluate the role of the IL-10 gene in IBD, two polymorphisms in the promoter region (G/A at position -1082 and C/A at position -592) were genotyped in 142 patients with Crohn's disease (CD), 104 patients with ulcerative colitis (UC), and 400 healthy controls. Significant differences were not apparent, neither in the allele frequencies of either polymorphism, nor in the haplotype frequencies. Screening of the coding region of the IL-10 gene by polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) analysis revealed a rare sequence variation in exon 1 leading to an amino acid exchange (G-->A; G15R) in two patients with CD and five healthy controls. Therefore, polymorphisms of the IL-10 gene are not demonstrably involved in the predisposition of IBD in our cohorts of patients.

Colitis, Ulcerative↗

PubMed2000

Interferon-alpha-2b + ribavirin for the treatment of chronic hepatitis C in non-responders to interferon-alpha-monotherapy.

UNLABELLED: The efficacy of a therapy with interferon-alpha-2b and ribavirin in patients with hepatitis C not responding to the initial treatment remains controversial. Objective of the present study was to determine the efficacy of a combination therapy with 3 MU interferon-alpha thrice weekly and 1,000-1,200 mg ribavirin daily for six months in an open label trial. METHODS: 44 consecutive patients (genotype 1: 79.5%) who had been previously treated with a minimum dose of 3 MU interferon-alpha thrice weekly for at least three months were monitored. Sustained response was defined as virological response with clearance of HCV-RNA after a follow-up period of six months after the end of therapy. RESULTS: A significant decrease of the mean levels of AST (34.3 +/- 27.6 vs. 16.4 +/- 13.5 U/L) and ALT (59.6 +/- 48.8 vs. 23.2 +/- 20.7 U/L) was observed. In 15/44 patients (34.1%) a virological end-of-treatment response was evident. 8/44 patients (18.2%) achieved a sustained response. In 33.3% of the previous non-responders biochemical response with normal aminotransferases, but no virological response was evident. A significant decrease of the mean hemoglobin level was observed during therapy (12.0 +/- 1.7 vs. 14.6 +/- 1.0 g/dl; p < 0.005), which returned to the pretreatment values after the end of treatment (14.4 +/- 1.6 g/dl; n.s.). In ten patients (22.7%) decrease of hemoglobin levels < 10 g/dl led to a dose reduction of ribavirin. CONCLUSION: This study--in agreement to recently published data--provides evidence for the efficacy of the combination therapy with interferon-alpha-2b and ribavirin in a relevant subset of non-responders to interferon-alpha. Therapeutic nihilism should be reevaluated in non-responders to interferon-alpha.

Adult↗

PubMed2000

Overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis in two cases.

The overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis is a rare condition and only few cases have been published, partly associated with ulcerative colitis, but not with Crohn's disease. We report an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in a female patient with Crohn's disease. In addition, a second case of overlap syndrome is reported in a man without inflammatory bowel disease. A 24-year-old woman was referred with a 10-month history of diarrhoea and biochemical changes including elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and immunoglobulin G. Enzyme linked immunosorbent assay showed that antinuclear autoantibodies were elevated. Immunofluorescence for perinuclear-staining antineutrophil cytoplasmatic antibodies was positive. Diagnostic criteria of definite autoimmune hepatitis according to the International Autoimmune Hepatitis Group were fulfilled. Liver biopsy simultaneously showed criteria of autoimmune hepatitis and primary sclerosing cholangitis. Endoscopic retrograde cholangiography demonstrated features of primary sclerosing cholangitis. Colonoscopy and colonoscopic biopsies indicated an active Crohn's disease affecting the terminal ileum and the ascending and transverse colon. Furthermore, we report the case of a 28-year-old man with known primary sclerosing cholangitis for the previous 6 years, and who developed jaundice and a marked increase of aspartate aminotransferase, alanine aminotransferase and immunoglobulin G, leading to the diagnosis of definite autoimmune hepatitis. A review of the literature revealed only 16 cases of an autoimmune hepatitis/primary sclerosing cholangitis syndrome in patients without inflammatory bowel disease or in association with ulcerative colitis. We report two additional cases, one case showing an association with Crohn's disease.

Adult↗

PubMed1999

[Extra-intestinal manifestations and complications in chronic active ulcerative colitis in childhood and adolescence].

HISTORY AND CLINICAL FINDINGS: A 18-year-old girl suffered from chronic active ulcerative colitis for ten years with growth retardation, primary amenorrhoea and osteopenia, so that total colectomy had been discussed as a possible treatment option. However, clinical remission was reached using a medication with budesonide (9 mg), mesalazine (3 g) and azathioprine (100 mg) when a painful ulcer occurred at the right lower leg. INVESTIGATIONS: The clinical examination revealed an ulcer of 7 cm diameter with a red-bluish margin at the right lower leg. The typical clinical features led to the diagnosis of pyoderma gangrenosum. TREATMENT AND COURSE: High doses of orally administered prednisolone induced the healing of the pyoderma gangrenosum within 2 months. After another 2 months systemic steroids were discontinued. Further laboratory tests confirmed secondary adrenal and ovarian failure (negative CRH-GnRH-test). Change of drug therapy to hydrocortisone (25 mg) in combination with mesalazine (3 g) and azathioprine (100 mg) improved the clinical course. Hydrocortisone was gradually reduced until CRH-GnRH-response returned to normal. CONCLUSION: Drug therapy with azathioprine can be regarded as a treatment option in pediatric patients with chronic active inflammatory bowel disease. It can be concluded from this case report that faced with controversial therapeutic options in adolescent patients the decision mainly depends on the clinical experience of the physician than on the results of controlled clinical trials.

Adolescent↗

PubMed1999

Polymyositis of the skeletal muscles as an extraintestinal complication in quiescent ulcerative colitis.

Myositis of the skeletal muscle is a rare complication of inflammatory bowel disease. We report about a 33-year-old woman with quiescent ulcerative colitis known since 1995. She had suffered from recurring fever and pain in the thighs for about 4 weeks. Electromyography of quadriceps and deltoid muscles revealed myopathic changes. Diagnosis of polymyositis was confirmed by magnetic resonance imaging indicating edematous changes in the distal extremity muscles. The symptoms rapidly responded to high doses of steroids. Review of the literature indicates only a few cases describing an association of ulcerative colitis and myositis, most of them during acute exacerbations of the disease. In contrast, the present patient was in remission. Diagnosis of myositis should be considered in inflammatory bowel disease patients complaining of myalgia or muscular weakness. Magnetic resonance imaging may show specific features and can be used in addition to laboratory investigations and muscle biopsy for diagnosis of polymyositis.

Adult↗

PubMed1999

Vascular endothelial growth factor (VEGF) in Crohn's disease: increased production by peripheral blood mononuclear cells and decreased VEGF165 labeling of peripheral CD14+ monocytes.

Recently, increased serum levels of vascular endothelial growth factor (VEGF) have been shown in patients with inflammatory bowel disease. The origins of the circulating VEGF are still not described. Monocytes play an important role in the inflammatory process. VEGF binding to monocytes mediates monocyte recruitment and activation. The present study investigates the VEGF production of peripheral blood mononuclear cells and the ability of peripheral monocytes to bind VEGF165 in patients with Crohn's disease. Nineteen patients with Crohn's disease and 10 healthy volunteers were studied. VEGF165 labeling of CD14+ monocytes was measured using two-color flow cytometry. Density of VEGF labeling was expressed as the mean fluorescence intensity (MFI). Furthermore, VEGF levels were determined in culture supernatants of unstimulated peripheral blood mononuclear cells. VEGF in culture supernatants was measured using a solid-phase enzyme-linked immunosorbent assay. There was a significantly decreased VEGF165 labeling of monocytes of patients with active Crohn's disease (MFI: 369.9+/-121.6, N = 7, P < 0.002) compared to patients with inactive disease (MFI: 457.7+/-74.5, N = 6) and healthy controls (MFI: 542.9+/-96.2, N = 10). Unstimulated peripheral blood mononuclear cells of patients with active Crohn's disease produced significantly higher amounts of VEGF (1142.6+/-483.9 pg/ml, N = 12, P < 0.001) compared with peripheral blood mononuclear cells of healthy volunteers (113.4+/-101.8 pg/ml, N = 10). VEGF production by peripheral blood mononuclear cells of patients with active disease was significantly increased compared to patients with quiescent disease (261.6+/-254.8 pg/ml, N = 7, P < 0.001). In conclusion, our data describe peripheral blood mononuclear cells as one of the origins of the elevated VEGF serum levels in patients with active Crohn's disease. Furthermore, a decrease in VEGF165 binding sites on peripheral monocytes of patients with active Crohn's disease has been shown. The study underlines the important role of VEGF in Crohn's disease.

Adolescent↗

PubMed1999

Budesonide for the treatment of collagenous colitis: first results of a pilot trial.

OBJECTIVE: Collagenous colitis is a chronic watery diarrhea disorder characterized by a subepithelial collagen layer and a lymphoplasmacytic infiltration within the lamina propria. However, no standard treatment has been introduced by controlled clinical trials. Aim of the present pilot trial was to investigate the clinical effects of orally administered budesonide (3 mg t.i.d.) in 7 patients with collagenous colitis. In addition, the histomorphological changes after budesonide treatment were described in a group of 3 patients. METHODS: The study was performed as an open label pilot trial. Study end point was the clinical remission of collagenous colitis defined by stool frequency and stool consistency. RESULTS: The results indicate a rapid and sustained clinical response in all patients. Stool frequency significantly decreased (p < 0.001) from 10.43 +/- 5.56 per day (4-20 per day) to 3.3 +/- 1.2 (1-5 per day) after 10 days and to 1.86 +/- 0.69 per day (1-3 per day) after 10 wk. Moreover stool consistency changed from watery (6 patients) or soft (1 patient) to soft (1 patient) or solid (6 patients). Clinical improvement was achieved within the first 10 days in all patients and maintained after dose reduction. In 3 patients no diarrhea recurred within 7, 12, or 15 months after treatment with budesonide was terminated. In these patients control biopsies were taken and showed a marked regression of both characteristics, the collagen band and the lymphoplasmacytic infiltration. CONCLUSIONS: With respect to the preliminary data from this pilot trial, budesonide with its high topical and low systemic effects seems to be of therapeutic clinical benefit in collagenous colitis. A therapeutic effect could be demonstrated for both therapeutic goals, the clinical response and morphological changes. Further studies on the effects of budesonide on mucosal collagen metabolism and long-term follow-up are warranted.

Anti-Inflammatory Agents↗