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BACKGROUND Cholesteryl ester storage disease (CESD), also known as lysosomal acid lipase deficiency (LAL-D), is a rare autosomal-recessive inheritable lysosomal storage disease. Since 2015, a causal treatment with sebelipase alfa, which replaces the missing LAL enzyme, has been approved. We report a fatal course of LAL-D in a female patient. CASE REPORT In 1979, CESD was first diagnosed in a 13-year-old female with marked hepatomegaly. At that time, no specific treatment for CESD was available and the spontaneous course of the disease had to be awaited. In 2013, a laparoscopic cholecystectomy for symptomatic gallstones was performed. The patient's CESD had caused a Child-Pugh A/B and Lab-MELD 14 cirrhosis with esophageal varices (grade III), a solitary fundal varix, as well as hepatosplenomegaly with thrombocytopenia. In 2016, the patient was admitted with compensated cirrhosis and splenomegaly for a ligature of esophageal varices which was complicated by vomiting of blood followed by severe coagulopathy and hemorrhagic shock. The dried blood test showed reduced acid lipase (0.03 nmol/spot*3 hours; reference range 0.2-2) and beta-galactosidase (0.08 nmol/spot*21 hours; reference range 0.5-3.2). Then 15 days after the esophageal varices bleed, the patient died due to multiorgan failure as a sequelae of advanced liver disease. CONCLUSIONS LAL-D should be included in the differential diagnosis of lipid metabolism disorder, hepatomegaly, and non-alcoholic fatty liver disease with fibrosis or cirrhosis. Causal treatment with sebelipase alfa should be introduced even in patients who have LAL-D and many years of clinically mild symptoms of this disease to prevent the serious sequelae of cirrhosis or cardiovascular complications.

Background & Aims: Comparative data on budesonide vs mesalamine for the treatment of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the efficacy and safety of each therapy in patients with mildly to moderately active CD., Methods: We performed a randomized, double-blind, double-dummy, 8-week, multicenter study in which 309 patients with mildly to moderately active CD received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3 times daily) or Eudragit-L-coated oral mesalamine (4.5 g/day)., Results: The primary efficacy variable, clinical remission (defined as Crohn's Disease Activity Index ≤150), at the final visit occurred in 69.5% (107 of 154) of patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine (difference, 7.4%; 95% repeated confidence interval, -4.6% to 18.0%; P = .001 for noninferiority). Clinical remission rates did not differ significantly between the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity Index of 150 or less and/or a decrease of 70 or more (Δ70) or 100 or more (Δ100) points from baseline to final visit, did not differ significantly between patients given budesonide vs mesalamine (Δ70, P = .11; Δ100, P = .15), or between the 2 budesonide groups (Δ70, P = .38; Δ100, P = .78). No other efficacy end points differed significantly between groups. Discontinuation because of adverse events occurred in 3% and 5% of budesonide- and mesalamine-treated patients, respectively. There were no clinically relevant differences in adverse events between the 2 budesonide groups., Conclusions: Budesonide (9 mg/day) was numerically, but not statistically, more effective than Eudragit-L-coated mesalamine (4.5 g/day) in patients with mildly to moderately active CD. Budesonide (9 mg/day), administered once daily, was as effective as the standard (3 times daily) regimen., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We report about a 56-year-old asymptomatic female patient, who was examined in April 1991 for an increase of biochemical parameters of the liver. Based on the biochemical and serological results (abnormal cholestatic liver function tests, positive antimitochondrial antibodies) as well as liver biopsy primary biliary cirrhosis stage I was diagnosed. Therapy with ursodeoxycholic acid (12mg/kg body-weight/die) was started. Follow-up examinations indicated that cholestatic parameters had normalized and antimitochondrial antibodies became negative. In a further biopsy of the liver nearly regular liver parenchyma was demonstrated. Thus, therapy with ursodeoxycholic acid was stopped. However, in November 1992 cholestatic parameters increased again and, antimitochondrial antibodies recurred (subtype anti-M9: positive) without any clinical symptoms. Ursodeoxycholic acid therapy was reintroduced again. Within 3 months cholestatic parameters returned to normal and antimitochondrial antibodies were eliminated again. Since then ursodeoxycholic acid has been given continuously and a long-term remission as defined by clinical, serological and histological criteria could be maintained until today. This case report indicates a serological remission and a marked histological improvement in a female patient with an early stage of primary biliary cirrhosis (stage I) during therapy under ursodeoxycholic acid. It has to be discussed whether certain early stages of primary biliary cirrhosis with benign antimitochondrial antibody-profile (anti-M9: positive) respond well to long-term treatment with ursodeoxycholic acid.

Background: The bactericidal/permeability increasing protein (BPI) is involved in the elimination of gram-negative bacteria. A functionally relevant single nucleotide polymorphism of the BPI gene causes an amino acid exchange (Glu216Lys)., Study: To evaluate whether this single nucleotide polymorphism contributes to the predisposition to inflammatory bowel disease, we compared the allele frequencies of 265 patients with Crohn's disease, 207 patients with ulcerative colitis, and 608 healthy controls., Results: The Glu/Glu genotype frequency was decreased significantly in Crohn's disease patients as compared with controls (P < 0.027). No differences were obvious in patients with ulcerative colitis., Conclusions: Failure of the innate intestinal immune system could be involved in the pathogenesis of Crohn's disease via reduced/impaired defense against gram-negative bacteria.

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.

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.

Objectives: Collagenous colitis is a chronic inflammatory bowel disease with a band-like subepithelial deposition of immature extracellular matrix. Because the extracellular matrix deposition is potentially reversible, an imbalance between fibrogenesis and fibrolysis with reduced matrix degradation has been suspected. Vascular endothelial growth factor plays a central role in extracellular matrix degradation. Therefore, we investigated the expression of vascular endothelial growth factor in the colonic mucosa of patients with collagenous colitis before and after long-term treatment with oral budesonide., Method: A quantitative immunohistochemical method was used to measure the amount of immunoreactive vascular endothelial growth factor, tenascin and leucocyte common antigen within the epithelium and the lamina propria of colonic biopsies by area morphometry., Results: Strong immunostaining for vascular endothelial growth factor within the epithelium and the lamina propria, and for tenascin, was seen in patients with collagenous colitis compared with normal controls. The enhanced immunostaining for vascular endothelial growth factor within the lamina propria was accompanied by the accumulation of leucocytes, detected by staining for leucocyte common antigen. After long-term treatment with oral budesonide, the amount of immunostaining for leucocyte-derived vascular endothelial growth factor within the lamina propria decreased significantly to normal levels. In contrast, staining for vascular endothelial growth factor within the epithelium remained significantly increased., Conclusions: Our data suggest an important role of vascular endothelial growth factor in counteracting the local imbalance of fibrogenesis and fibrolysis, leading to an accumulation of immature subepithelial matrix in collagenous colitis.

Background and Aims: Nuclear factor kappa-B (NFkappaB) plays a crucial role in diseases associated with dysregulated immune response. NFkappaB inhibitor alpha downregulates the activity of NFkappaB., Patients and Methods: To evaluate the contribution of the NFkappaB inhibitor alpha gene in Crohn's disease single nucleotide polymorphisms in the 3'-UTR and at position -420 in the promoter were studied in 259 patients with Crohn's disease genotyped for the variations of the CARD15 gene in comparison to 441 healthy controls. Additionally we screened the coding region of the NFkappaB inhibitor alpha gene for polymorphisms by SSCP analysis., Results: In comparison to controls the A allele and the AA genotype frequencies of the single nucleotide polymorphisms in the 3'-UTR were significantly increased only in Crohn's disease patients without a variation in the CARD15 gene. Similarly, the difference between patients harboring no predisposing CARD15 alleles and patients harboring such a variation was significant., Conclusion: The findings indicate that the phenotype Crohn's disease is to be substructured with respect to genetic susceptibility.

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.

History and Clinical Findings: A 61-year-old male patient complained about diffuse upper abdominal pain and a progressive dyspnoe on exertion. Of clinical relevance were signs of congestive heart failure and a distinct kyphoscoliosis., Therapy and Clinical Course: A cardiac catheter examination proved a pulmonary hypertension without cardiac genesis. Both, pulmonary function test and computed tomography of the thorax rule out obstructive bronchial asthma and embolism of the lung. As the sole cause of pulmonary hypertension, kyphoscoliosis was diagnosed. Since the patient refused noninvasive positive pressure ventilation, a medication with calcium entry blocker and ACE blocker was induced, followed by oxygen breathing. This successfully helped to reduce pulmonary resistance (746 vs. 332 dyn*s*cm(-5))., Conclusion: Kyphoscoliosis can create a considerable increase of pulmonary resistance. Medical treatment and oxygen breathing have proven to be an efficient method to lower that significantly.

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.

Background & Aims: Collagenous colitis is an idiopathic microscopic colitis characterized by chronic watery diarrhea, a typical subepithelial collagen layer, and lymphoplasmacellular infiltration. We investigated the effect of budesonide on symptoms and histology in patients with collagenous colitis in a randomized, double-blind, placebo-controlled multicenter trial., Methods: Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral budesonide (Entocort capsules; AstraZeneca, Sodertalje, Sweden) 9 mg/day for 6 weeks or placebo. Complete colonoscopy was performed before and after treatment. Histopathology was assessed by a single pathologist blinded to the patients' treatment. Clinical symptoms were assessed by standardized questionnaires., Results: Fifty-one patients were randomized; 45 patients were available for per protocol analysis. The rate of clinical remission was significantly higher (P < 0.001) in the budesonide group than in the placebo group (per protocol 86.9% vs. 13.6%, respectively; intention-to-treat 76.9% vs. 12.0%, respectively). Histologic improvement was observed in 14 patients of the budesonide group (60.9%) and in 1 patient of the placebo group (4.5%; P < 0.001). Two patients in the budesonide group (7.7%) and 1 patient in the placebo group (4.0%) discontinued treatment prematurely because of side effects., Conclusions: Oral budesonide (Entocort capsules) is an effective and safe treatment modality for patients with collagenous colitis. Long-term follow-up of these patients is necessary to investigate whether clinical and histologic remission is sustained.

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.

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.

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.

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.

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.

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.

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.

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.

Background/aims: Vascular endothelial growth factor (VEGF), a potent angiogenic, permeability-enhancing cytokine plays an important role in tissue repair and chronic inflammatory disorders. Peripheral blood mononuclear cells (PBMCs) and the inflamed mucosa have been demonstrated to be main sources of the recently described circulating VEGF in patients with inflammatory bowel disease (IBD). There is no current information about the influence of immunoregulatory cytokines on VEGF in IBD. The present study examines the effect of interleukin-4 on the increased VEGF production of PBMCs in patients with IBD., Methodology: Unstimulated PBMCs from 17 patients with Crohn's disease, 16 patients with ulcerative colitis and 8 healthy controls were cultured with or without IL-4. VEGF production was measured in the supernatant using an enzyme-linked immunosorbent assay., Results: IL-4 led to a significant reduction of the VEGF production by PBMCs of both active Crohn's disease patients (471.7 +/- 377.5 pg/mL vs. 208.2 +/- 123.2 pg/mL, P = 0.018, n = 7) and active ulcerative colitis patients (177.1 +/- 79.4 pg/mL vs. 87.4 +/- 77.2 pg/mL, P = 0.008, n = 9). IL-4 inhibited significantly the VEGF production by PBMCs of patients with inactive Crohn's disease (179.2 +/- 133.9 pg/mL vs. 87.7 +/- 56.6 pg/mL, P = 0.005, n = 10). There was no significant difference of VEGF release by PBMCs cultured with IL-4 in patients with active Crohn's disease or active ulcerative colitis compared with PBMCs cultured without IL-4 in patients with inactive disease and healthy controls (112.6 +/- 41.9 pg/mL, n = 8)., Conclusions: IL-4 has been shown to reduce the increased VEGF production of PBMCs in patients with IBD to normal levels. The known defective immunosuppressive effect of IL-4 in IBD may contribute to the pathogenic cascade leading to inflammation by VEGF mediated mechanisms.

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.

Background/aims: In patients with liver cirrhosis and upper gastrointestinal bleeding development of hepatic encephalopathy is a major problem. The aim of the present study was to evaluate the efficacy of the mannite lavage in a controlled randomized trial with respect to the Child-Pugh classification., Methodology: After initial gastroscopy (+/- sclerotherapy) 39 patients with cirrhosis (18 F, 21 M; age: 57.5 +/- 11.9 yr; Child A: 6, Child B: 16, Child C: 17) and upper gastrointestinal-bleeding were classified according to the Child-Pugh-criteria (A,B,C) and randomized in 2 groups (A,B) for each Child-Pugh level. Patients in group A (n = 18) were initially treated with 2000 mL mannite solution (10%) during the first 2 hours using a naso-gastric tube. Treatment was continued using 2000 mL mannite solution (10%) per day until no rectal blood could be observed. Patients in group B (n = 21) were treated with paromomycine ter in die (1 g tid) and lactulose (10 mL tid). There were no statistical differences between both groups concerning age, sex, Child-Pugh-scores, severity or source of bleeding, initial hemoglobin-levels, number of given blood-transfusions or number of patients with sclerotherapy., Results: Patients in group A were treated with a total of 3325 +/- 1897 mL mannite solution. The application was well tolerated. In addition, kinetics of serum creatinine, potassium and sodium levels did not show any significant changes. No significant differences between both groups could be shown with respect to clinical criteria of encephalopathy according to O'Grady and the length of intensive care unit treatment. Moreover, kinetic of ammonia-levels showed a pronounced decrease (P = 0.05) on day 2 versus day 1 in group A (110.0 +/- 24.2 vs. 156.4 +/- 98 mg/dL) as compared to group B (210.0 +/- 52.7 vs. 162.0 +/- 45 mg/dL). In group A, 6 patients (33.3%) died during the study as compared to 3 patients (14.3%) in group B (P > 0.05). The lethality rate was strongly associated with the larger proportion of Child-C-patients in group A., Conclusions: The data indicate that whole gut irrigation with mannite is equally efficacious as compared to standard treatment for prophylaxis of hepatic encephalopathy after upper gastrointestinal bleeding in liver cirrhosis. In contrast to previously published controlled studies, no impact of the lavage on the mortality rate or duration of intensive care unit treatment could be shown. With respect to the lower costs for the mannite solution as compared to paromomycine and lactulose (ROTE LISTE, Germany), the mannite lavage should be recommended for the prophylaxis of hepatic encephalopathy after upper gastrointestinal bleeding in patients with liver cirrhosis.

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.

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.

The release of 5-ASA from various preparations depends on the presence of bacterial azoreductases (sulphasalazine, olsalazine, balsalazide) or the pharmacokinetic properties of the mesalazine-containing pharmaceutical preparations. The differences of the 5-ASA release from the various preparations account for the different anatomic sites of actions. In this regard, a close relationship between the regional intraluminal concentrations of 5-ASA and the clinical response can be assumed. The aim of the present paper is to survey clinical trials in Crohn's disease with special respect to the pharmacokinetic properties of the used mesalazine containing preparations. There are clear differences between the different coated 5-ASA formulas in respect to 5-ASA release and in respect to their pharmacokinetic properties leading to a different therapeutic efficacy in Crohn's disease. The detailed analysis indicates that higher doses of 5-ASA (> 3 g/d) are required for the acute phase treatment. 4.5 g Eudragit-L-coated 5-ASA tablets are almost equally as potent as glucocorticosteroids for the treatment of active Crohn's disease. Clinical efficacy has been demonstrated for Eudragit-L-coated tablets even at a low dose of 1-1.5 g 5-ASA/day in the maintenance treatment of remission of Crohn's disease. This has also been shown for Eudragit-S-coated tablets at a dose of 2.4 g 5-ASA/day, while even 3 g 5-ASA of an Eudragit-L/S formula as well as the ethylcellulose-coated formulas up to 4 g 5-ASA/day were ineffective, except for a high risk group. On the basis of the published trials, there is clear evidence that post-operative prophylaxis with 5-ASA requires daily doses higher than 1.5 g. Ethylcellulose-coated 5-ASA has only been effective in Crohn's disease limited to the small bowel and should not be given to patients with ileo-colonic or colonic disease. Moreover, Eudragit-L-coated 5-ASA preparations have shown to be effective in both ileal and colonic disease concerning their clinical efficacy in post-operative prophylaxis. In contrast, endoscopic efficacy has been demonstrated for ethylcellulose as well as Eudragit-S-coated formulas. Treatment of Crohn's disease with orally administered 5-ASA can generally be regarded as an effective and well-tolerated therapy. However, the distinct therapeutic goal (acute phase treatment, maintenance therapy or post-operative prophylaxis), the involved areas of the gut and the specific release of the drug administered have to be considered.

Objective: Lymphocytopenia is a sensitive surrogate marker for the immunological effects of corticosteroids. This pharmacokinetic/pharmacodynamic (PK/PD) study investigated whether the circadian variation of blood lymphocytes observed after placebo is secondary to the circadian rhythm of endogenous cortisol, and developed based on this relationship an improved PK/PD model for a more sensitive description of the effect of low-dose corticosteroid therapy on blood lymphocytes considering the net activity of the exogenous corticosteroid budesonide and endogenous cortisol., Methods: In an open, parallel study design, 3 mg oral budesonide or placebo were given at 8.00 a.m., 4.00 p.m. and midnight to two groups of 12 volunteers. Lymphocyte counts and serum concentrations of budesonide and cortisol were monitored for 24 hours. A mechanism-based PK/PD model which considered the non-linear protein binding of cortisol and the budesonide-induced cortisol suppression was employed to relate changes in blood lymphocytes to free cortisol levels after placebo and to the net activity of free budesonide and free endogenous cortisol after active treatment., Results: The circadian rhythm of blood lymphocytes observed after placebo could inversely be related to the circadian rhythm of serum cortisol. After budesonide administration, lymphocyte counts could accurately be linked to the net activity of budesonide and endogenous cortisol. The resulting EC50 values for the effect of budesonide on cortisol, budesonide on lymphocytes and cortisol on lymphocytes were 0.063 +/- 0.034, 0.22 +/- 0.13 and 26.3 +/- 15.0 ng/ml (placebo group 15.4 +/- 3.4 ng/ml), respectively., Conclusions: The presented mechanism-based PK/PD model suggests that blood lymphocytes are under physiological control of cortisol. It further indicates that endogenous and exogenous corticosteroids and their pharmacological interaction need to be considered for modeling the effects of low doses of exogenous corticosteroids on the immune system.

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.

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.

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.

A 27-year-old woman was successfully treated with a highly dosed steroid therapy over several months during summer 1994 in the event of urticaria. In October 1994, when the patient was complaint free, therapy was abruptly terminated. In November 1994 jaundice, nausea and loss of appetite occurred. Biochemical results showed markedly elevated serum transaminases, negative hepatitis serology, normal immunoglobulins and inconspicious autoantibodies. Histology showed a florid hepatitis. In January 1995 the patient was hospitalized again in very low general and nutritional condition with a marked jaundice, high serum transaminases, insufficient liver synthesis function, established ANA(+), ASMA(+2) and normal immunoglobulins. This time histology painted out an active hepatitis going into liver cirrhosis. Evaluation in view of liver transplantation was carried out in this case of liver failure. At that time, tests showed a distinct gamma globulin fraction increase although the antibody pattern had remainded identical. An immunosuppressive therapy with azathioprine and steroids was decided upon under suspicion of an autoimmune hepatitis leading to a prompt positive response and therefore confirmation of the diagnosis. Complete biochemical remission was attained in April 1995 and a complete histological remission in March 1998.

Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic, vascular permeability-enhancing, and calcium-dependent enzyme-modulating cytokine with overexpression in various pathologic disorders, including granulomatous inflammation, tissue repair, delayed hypersensitivity reactions, rheumatoid arthritis, and tissue ischemia. The present study investigates the role of VEGF in chronic inflammatory bowel disease., Methods: Thirty-one patients with Crohn's disease, 15 patients with ulcerative colitis, and 9 healthy volunteers were studied. VEGF serum levels were measured with a solid-phase enzyme-linked immunosorbent assay., Results: Significantly increased VEGF serum levels were observed in both active Crohn's disease and active ulcerative colitis when compared with healthy controls. Patients with active Crohn's disease and active ulcerative colitis showed significantly higher VEGF serum levels than patients with quiescent disease. No difference was observed between inactive disease and healthy controls. In addition, strongly increased VEGF serum levels were found in patients with Crohn's disease with fistulas in the absence of clinical, endoscopic, histologic, and laboratory findings of disease activity., Conclusions: Significantly increased VEGF serum levels were observed in patients with active Crohn's disease and ulcerative colitis, which suggests that VEGF has an important role in chronic inflammatory bowel disease. Its possible association with fistulas has yet to be determined.

Unlabelled: Previous studies have shown high inter- and intraindividual variation coefficients (Vkinter; Vkintra) of the gastric emptying time t(end) determined by sonographical antrum planimetry., Purpose: Are there new parameters reflecting the functional process of gastric emptying?, Method: Gastric emptying of 300 ml water was studied in 20 healthy volunteers by sonographical antrum planimetry. 10 volunteers were examined a second time on another day., Results: High variation coefficients Vkinter (42%) and Vkintra (31%) could be demonstrated. Moreover, a correlation of r = +0.922 between tend and the maximal percentual increase of the antral area was evident. This relation is introduced as the functional-emptying-line (FEL)., Conclusion: Using the functional aspects of FEL, gastric emptying can be studied sonographically under functional aspects.

Topics of this review are the bronchopulmonary manifestations of gastroesophageal reflux disease, cirrhosis of the liver and chronic inflammatory bowel diseases. About 20% of patients with chronic obstructive airway disease show evidence of gastroesophageal reflux disease. Reflux bronchoconstriction seems to be of greater importance than microaspiration. First studies show the positive effects of acid inhibition by proton pump inhibitors on pulmonary symptoms. Hepatorenal syndrome is characterized by arterial hypoxemia with PaO2-values < 70 mm Hg. Different mediators (endotoxins, amines, polypeptides or allergens) are discussed. Furthermore, elevated levels of prostacycline, atrial natriuretic factor and platelet activating factor have been described. Recently published studies focused on the role of nitric oxide (NO). Patients with cirrhosis of the liver show a higher rate of a pathologically elevated airway resistance which might be induced by a reduced histamine clearance. Ascites leads to reversible restrictive airway disease. Bronchopulmonary manifestations in chronic inflammatory bowel diseases include obstructive and restrictive airway diseases, vascular or serosal changes and show low clinical evidence. In contrast, pathological changes of the common function tests were found in 30 to 50%. These findings may be induced by circulating immune complexes, vasculitis, increased permeability or a combined immune reaction of both, the bronchial and intestinal mucosa. Undesired effects of salicylates should be taken into account. This review shows that bronchopulmonary manifestations in diseases of the Gl-tract or the liver are more common than usually known and should be taken into clinical consideration.

Objective: Corticosteroids are effective in acute Crohn's disease (CD). The present study assessed the effectiveness and safety of oral pH-modified release budesonide (BUD) in patients with active CD in comparison with 6-methylprednisolone (MPred)., Design: This was a prospective multicentre, randomized, double-blind, double-dummy study., Methods: A total of 67 patients with active CD (CDAI > 150) were included. Patients were treated with 3 x 3 mg BUD (n = 34) or MPred (n = 33) according to a weekly tapering schedule (48-32-24-20-16-12-8 mg). The primary aim was remission of CD (CDAI < 150 and decrease by at least 60 points from baseline) after eight weeks., Results: Baseline demographics, disease activity and localization of CD in the small bowel and the colon were similar in both treatment groups. On an intention-to-treat basis 19/34 patients in the BUD group (55.9%) and 24/33 patients in the MPred group (72.7%) were in remission after eight weeks (P = 0.237). Therapy failed in 15/34 patients (44.1%) of the BUD group and in 9/33 patients (27.3%) of the MPred group. The mean CDAI decreased from 262 +/- 50 to 118 +/- 69 in the BUD-group and from 262 +/- 81 to 95 +/- 61 in the Mored group (P = 0.183, final CDAI BUD vs. MPred). Steroid-related side effects appeared in 28.6% of the patients in the BUD group and in 69.7% of the patients in the Mored group (P = 0.0015)., Conclusions: Oral pH-modified release budesonide (3 x 3 mg/day) is almost as effective as a conventional corticosteroid in patients with active CD but causes significantly less corticosteroid-related side effects.

During active inflammatory bowel disease (IBD) the respiratory burst of neutrophil granulocytes has been shown to be impaired using isolated circulating neutrophil granulocytes of patients with active disease. Using normal neutrophil granulocytes of healthy volunteers the present study examines the potential priming effect of sera of patients with active and quiescent IBD. The superoxide anion (O2-)-release of normal neutrophil granulocytes in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been investigated after incubation with sera of patients with active and inactive Crohn's disease and ulcerative colitis. O2(-)-release was measured using the superoxide dismutase inhibitable reduction of ferricytochrome c. The O2(-)-release of normal neutrophil granulocytes primed with sera of patients with inactive Crohn's disease (607.1 +/- 218.2 nmol/60 min, n = 10, p = 0.001) or cultured with sera of patients with quiescent ulcerative colitis (497.4 +/- 94.9 nmol/60 min, n = 3, p = 0.005) was significantly enhanced when compared with sera of normal controls (319.8 +/- 86.5 nmol/60 min, n = 10). There was no significant difference between priming with sera of patients with quiescent or active Crohn's disease (481.0 +/- 113.0 nmol/60 min, n = 5). Normal neutrophil granulocytes primed with sera of patients with active ulcerative colitis produce significantly larger amounts of O2- (809.5 +/- 256.9 nmol/60 min, n = 4, p = 0.001) when compared with sera of normal controls. The study shows that sera of patients with quiescent IBD as well as sera of patients with active disease have the potential to prime normal neutrophil granulocytes for an enhanced O2(-)-release in response to FMLP.(ABSTRACT TRUNCATED AT 250 WORDS)

82 consecutive outpatients with Crohn's disease (n = 52) and ulcerative colitis (n = 30) were examined ambulatory. Rheumatic complaints, objective results and diagnosis were correlated to the activity of the underlying illness and the extent of the bowel affected. 61% of the examined patients complaint about rheumatic pains. In two thirds this could be attributed to noninflammatory causes (30% insertion tendinitis. 16% degenerative arthritis, 16% wrong carriage), which appeared to be independent of the activity and severity of the underlying disease. One fourth of the rheumatic complaints was caused by inflammation (21% arthritis, 5% sacroileitis). In these cases a dependency on the disease activity and the extent of the colon involvement could be found. No cause was found for 12% of the rheumatic complaints. In patients with ulcerative colitis suffering from arthritis a significant increase of disease activity (Rachmilewitz index) could be shown as compared to ulcerative colitis patients without arthritis (p < 0.02). For patients with Crohn's disease no significant correlation between arthritis and disease activity could be established. In these cases the occurrence of arthritis was associated with the colon involvement (Chi2 = 8.48). The data indicate the high frequency of rheumatic complaints in inflammatory bowel diseases due to noninflammatory causes.

53 unselected patients with Crohn's disease (CD) (35 female, 18 men; mean age: 32.3 +/- 12.5 y.; mean duration of CD: 78.6 +/- 65.7 months) and 23 patients with ulcerative colitis (UC) (8 female, 15 men; mean age: 43.7 +/- 17.9 y.; mean duration of UC: 100.7 +/- 86.0 months) were examined by quantitative computertomography (lumbar spine 1-3). Incipient (manifest) osteopenia (OP) was defined as a reduced axial bone mineral density from -1 standard deviations (SD) to -2 (SD) (< -2SD) as compared to a control Group. Reduced bone mineral density was found in 30.2% (16/53) of patients with CD and 9% (2/23) with UC (p < 0.05). In particular 12/53 pts. (22.6%) with CD and 1/23 pts. (4.35%) with UC showed incipient OP, whereas 4/53 pts. (7.5%) with CD and 1/23 pts. (4.35%) with UC showed manifest OP. With respect to the location of CD the mean relative bone density (SD) was found to be significantly lower in patients with ileal involvement of CD (-0.88 +/- 0.8 SD; n = 39) as compared to patients with colonic involvement (-0.09 +/- 0.86 SD; n = 14) and UC (-0.09 +/- 0.55 SD; n = 23) (p < 0.05). No significant correlation to the duration of the disease was found. Previous therapy with steroids led to lower mineral bone density as compared to untreated patients. As a trend duration of steroid treatment and bone density were shown to be correlated inversely.(ABSTRACT TRUNCATED AT 250 WORDS)

The acute effect of metoclopramide on oesophageal motility was investigated prospectively in 33 consecutive patients (20 men and 13 women; mean age 60.5 +/- 12.6 years) with type I (n = 8) or type II (n = 25) diabetes. 15 patients had a peripheral sensory-motor polyneuropathy only and three just an autonomic cardial neuropathy. Both lesions were present in ten, none in five. No patient had oesophago-gastroduodenal lesions. Sphincter pressure, relaxation time, contraction amplitude and propulsion velocity of bolus-induced oesophageal peristalsis were measured manometrically after intravenous administration of 10 mg metoclopramide. Resting pressure in the lower oesophageal sphincter rose significantly by 26.7%, contraction amplitude in the tubular portion of the oesophagus by more than 30%, and propulsion velocity by more than 20% (P for each < 0.05). At the same time the amount of segmental and aperistaltic oesophageal contractions regressed significantly. The effect of metoclopramide was demonstrated regardless of the type of diabetes, duration of diabetes and any manifestation of autonomic cardial or peripheral sensory-motor neuropathy.

The aim of the study was to examine the effects of maintenance molsidomine therapy on portal and cardiac haemodynamics in patients with confirmed alcoholic or nonalcoholic liver cirrhosis and portal hypertension. Molsidomine is a selective reducer of preload without development of tolerance. 16 patients with portally decompensated cirrhosis of the liver following an initial or recurrent episode of bleeding form oesophageal/fundal varices were on long-term treatment (4-24 months) with 2 or 3 x 8 mg molsidomine/day (Corvaton retard). They were followed up after 3-6 months. 6 of the 16 had been treated previously with propranolol for haemorrhage prophylaxis over 11 +/- 15 months. In a total of 70 treatment months with propranolol, 10 recurrent bleeds had occurred. During 166 treatment months with propranolol, 10 recurrent bleeds had occurrences of bleeding. This long-term treatment showed reductions in hepatic venous pressure gradient of 24.8% (n = 8) (p < 0.05), variceal pressure of 28.7% (n = 7) (p < 0.05) and size of varices of 17% (n = 8). This occurred without any clinically relevant impairment of systemic cardiovascular regulation. Therefore long-term therapy with molsidomine may be suitable for prophylaxis of haemorrhage of oesophageal varices.

In 124 patients with Crohn's disease (69 women, 55 men; mean age 33.7 [11-66] years) and 53 with ulcerative colitis (30 women, 23 men; mean age 36.2 [19-74] years) the incidence of lactose intolerance, as measured by the H2 breath test and blood sugar concentration, was determined prospectively. To exclude abnormal bacterial colonization of the small intestine or rapid small-intestine transit after partial resection of the small intestine as a cause of lactose intolerance, the oro-caecal transit time for lactulose (H2 breath test) was measured. While 21 of 124 patients with Crohn's disease (16.9%) had the expected incidence of lactose intolerance, this was present in only 2 of 53 patients with ulcerative colitis (3.8%; P < 0.05). The lactose intolerance was independent of the site of any inflammatory changes, disease activity and extent of small-intestine resection. Oro-caecal transit time for lactose was similar for all patients. There was no lactose intolerance in two patients with abnormal small-intestinal bacterial colonization.--Because of their considerable diagnostic and prognostic significance, tests for lactose intolerance should be performed routinely in all cases of Crohn's disease or ulcerative colitis.

In a prospective study we compared the usefulness of various laboratory tests (albumin, alpha-1-proteinase inhibitor (A1PI), cholinesterase (CHE), C-reactive protein, erythrocyte sedimentation rate, hematocrit) and activity indices (CDAI, VHAI) in relation to the disease activity by endoscopic criteria. Except for hematocrit highly significant differences (p less than 0.0005) of the mean values of all test results were found for patients without or with slight mucosal lesions compared with patients with severe inflammation of the mucosa. Further analysis of the data indicates the highest test efficiency (84%), sensitivity (80%), and specificity (88.6%) for CHE. CHE showed good correlations to all other tests; the highest correlation was found between CHE and VHAI (r = -0.78). We suggest that a suppression of CHE synthesis mediated by endotoxins and cytokines rather than an increased intestinal loss explains the decreased CHE in severe Crohn's disease. It is concluded from the data that CHE is a useful test to assess the inflammatory activity of Crohn's disease.

An example of acute pancreatitis developing five weeks after initial treatment with 5-aminosalicylic acid (5-ASA) and methylprednisolone for severe Crohn's disease is reported in a 37 year old female patient. She had undergone cholecystectomy for gall stones some years earlier. There was no evidence of acute or chronic pancreatitis. No morphological changes of the upper gastrointestinal tract were found except for some irregularity of the main pancreatic duct and the secondary ducts on endoscopic retrograde pancreatography. Rechallenge with 5-ASA did not induce recurrent pancreatitis or changes in pancreatic enzymes. This case report supports the concept of an association between acute pancreatitis and Crohn's disease.

Significantly decreased levels of serumcholinesterase (CHE) were found in acute Crohn's disease (= CD) (3.2 +/- 1.0 KU/L) and acute ulcerative colitis (= UC) (3.54 +/- 1.6 KU/L) as compared to patients with mild or quiescient disease (CD: 5.5 +/- 1.1 KU/L; UC: 5.59 +/- 0.94 KU/L) and healthy controls (5.69 +/- 1.3 KU/L). Suppression of CHE was most evident in Crohn's colitis (2.98 +/- 1.0 KU/L) and extensive UC (2.96 +/- 1.28 KU/L). Intraindividual comparison showed an increase of CHE-levels during treatment with steroids and salicylates. There was no significant correlation to the reduced bodyweight-levels in severe IBD. Best correlations were seen between CHE/albumin (CD: r = +0.61; UC: r = +0.73) and CHE/hematocrit (CD: r = +0.50; UC: r = +0.61) in severe inflammatory bowel disease. The results of a discriminant analysis showed that CHE-levels can predict the degree of activity correctly in the majority of patients with CD and UC. It is suggested that the decrease of serumcholinesterase reflects an inhibition of liver synthesis as an acute phase response-induced by endotoxins and cytokines.