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.

Platelet activating factor in stool from patients with ulcerative colitis and Crohn's disease.

BACKGROUND/AIMS: Platelet activating factor (PAF) is a potent endogenous mediator in inflammatory processes. The role of this mediator, especially in connection with the unknown etiology of chronic inflammatory bowel diseases, remains poorly understood. A determination of PAF in stool may be helpful in recognizing quiescent inflammations in chronic inflammatory bowel diseases. A simple and reliable method for the determination of PAF in stool seems to be necessary to achieve this goal. METHODOLOGY: PAF analysis was performed with the help of a commercial PAF radioimmunoassay (RIA) kit after solid phase extraction (SPE) of ethanolic stool extracts. PAF was determined in stool from 10 healthy volunteers (m = 4; f = 6), 13 patients with ulcerative colitis (m = 7; f = 6) and 15 patients with Crohn's disease (m = 9; f = 6). Fecal PAF concentrations were compared with activity index of disease, endoscopic index, localization of lesions, leukocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), medical prednisolone treatment, sex and age of the patients. RESULTS: In healthy volunteers, no PAF was detectable in stool. In patients with Crohn's disease 319.2 +/- 143.5 pg PAF/g stool and in patients with ulcerative colitis 824.9 +/- 408.7 pg PAF/g stool could be determined. A significant correlation (p < 0.05) was found between PAF-content in stool and the endoscopical index and intestinal localization of inflammatory lesions. No further correlations could be detected in our patients. CONCLUSIONS: Fecal PAF assessment may be used clinically as a non-invasive method to estimate severity of mucosal inflammation in patients with inflammatory bowel disease (IBD).

[The value of endoscopic retrograde cholangiopancreaticography in the diagnosis of bile duct and pancreatic diseases. Results of 756 studies]. / Die Bedeutung der endoskopischen retrograden Cholangiopankreatikographie bei Gallenwegs- und Pankreaserkrankungen. Ergebnisse von 756 Untersuchungen.

Endoscopic retrograde cholangiopancreatography was successful in 626 of 756 examinations (82,8%). Choledocholithiasis in view of bile ducts and chronic pancreatitits on the score of bile ductal system are the most lesions we could observe. An acute pancreatitis in 2 cases and an infection of a pancreatic pseudocyst in 1 case were the 3 complications in our material. Meanwhile the rate of successful cannulations reached more than 90%.

[Estimations of the serum levels of sulfapyridine on patients treated with sulfasalazin (author's transl)]. / Serumsulfapyridinspiegel-Bestimmungen bei Patienten unter einer Sulfasalazin-Behandlung.

Estimations of the serum level of sulfapyridine in 21 patients suffering from colitis ulcerosa or Crohn's disease, have been carried out. Nearly 50 per cent of all the serum levels were within the therapeutic range between 20 and 50 micrograms/ml. Some factors influencing the sulfasalazine metabolism are mentioned. The estimation of the serum levels of sulfapyridine is a suitable method for supervision of patients receiving treatment with sulfasalazine.

[Determination of sulfapyridine levels in serum--a possibility for the control of dose related therapy with sulfasalazine]. / Die Bestimmung des Sulfapyridinspiegels im Serum--eine Möglichkeit der Kontrolle einer dosisgerechten Therapie mit Sulfasalazin.

For determination of the sulphapyridine level there were used 83 sera of 57 patients with Crohn's disease or ulcerative colitis which were treated with salazosulphapyridine. In 22,8 percent there was a sulphapyridine level higher than the therapeutic range of the whole sulphapyridine of 20-50 micrograms/ml. The serum levels are below this range frequently. Sulphonamide containing drugs yield too high values. Generally no sulphapyridine is shown in the serum because of the missing splitting of the salazosulphapyridine in patients with colectomie. Low serum values are found at low patient-compliance. In diarrhoea sulphapyridine levels in the serum are decreased. Determination of the sulphapyridine level is suitable: a) for recognition of too high serum levels and therefore for prevention of side effects b) to make sure that the therapeutic range is reached.

[Fractionated determination of N-acetylneuraminic acid of the gastric juice in patients with Strickland type B chronic atrophic gastritis]. / Die fraktionierte Bestimmung der N-Azetylneuraminsäure des Magensaftes bei Personen mit einer chronisch-atrophischen Gastritis des Types B nach Strickland.

By the aid of fractional estimation of N-acetylneuraminic acid (NAN) from gastric juice it is possible to investigate quantitative changes of NAN-proteins on the gastric juice. Patients with active chronic atrophic gastritis of the type B have an increase of orosomucoid, which is precipitated by phosphorwolfram acid, in the gastric juice.

[Endoscopic laser therapy in gastroenterology--physical-technical principles and applications]. / Endoskopische Lasertherapie in der Gastroenterologie--Physikalisch-technische Grundlagen und Applikationen.

Since the mid-seventies the application of laser in gastroenterology for the treatment of haemorrhages and tumours has stood the test. At present the neodym-YAG-laser is the most important endoscopically applicable laser. The sources of laser radiation, the biophysical effects of laser and their fields of application, the technical and methodical and security-technical aspects as well as own divice-technical solutions and the indications in the application of the endoscopic laser therapy are described. In 12 out of 15 patients with a villous adenoma of the rectum the treatment was successful. In 9 patients with a high-degree stenosing rectosigmoid carcinoma (diameter 0.5 cm) the passage could be restored (diameter after treatment 1.3 cm). Complications did not appear. The laser therapy is effective, poor in risks, but not cheap.

[Endoscopic laser treatment of neoplasm and tubulovillous adenoma of the rectosigmoid. Initial experiences and review of the literature]. / Endoskopische Lasertherapie beim Malignom und tubulovillösen Adenom des Rektosigmoids. Erste Erfahrungen und Literaturübersicht.

With laser it's possible to produce a radiation of definite wave length which is rich in energy. This energy is changed into heat during its impinge on tissue. Different effects (coagulation, vaporization) can be produced in dependence on wave length, the technical features of laser and the different interaction of laser light. In 8 patients with obstructive polypous carcinomas of rectosigmoid a complete passage-recovery could be achieved. The therapy was effective in 8 out of 11 patients with villous adenomas. One patient had a relapse into adenoma after half a year. With laser a distal rectostenosis at high degree could be widened at Morbus Crohn. Complications didn't appear. Indications of laser-therapy are explained. The laser-therapy is effective, not very risky but not cheap. Therefore it requires an application of overlapping subjects.

[Emergency endoscopy in chronic liver diseases]. / Notfallendoskopie bei chronischen Lebererkrankungen.

Emergency endoscopy has to be regarded as a method of high diagnostic value. Based on the resulting therapeutic consequences and with allowance for the prerequisites and contraindications, emergency endoscopy in chronic liver diseases is to be considered a purposeful method. If endoscopic treatment possibilities in bleedings of the gastrointestinal tract continue to improve, the demonstration of an improvement in prognosis by emergency endoscopy seems to be merely a question of time.

[Early stomach cancer in our clinical sample]. / Das Magenfrühkarzinom im eigenen Krankengut.

In the period from 1971 to 1980 we studied 11 650 patients undergoing endoscopy of the stomach. We found in 427 patients a gastric cancer. In 63 patients we found an early cancer, according to 14% of all gastric cancers. The main symptoms were pain and loss of appetite. In 34% of the patients the duration of complaints was more than 1/2 year. In more than 50% the early cancer was located in the distal part of stomach. In 52% we observed the ulcerative lesion of the gastric mucosa. The histological findings were in 52% the intestinal type and in 72% the diffuse type of early gastric cancer. The precise diagnosis of an early cancer based on the histological examination of the gastric wall after gastric resection, with the exception of loopectomy and polypectomy with well-defined diagnosis of an early cancer. By the aid of preventive examination of patients with so-called precancerous condition of the gastric mucosa we see a possibility to increase the detection of early gastric cancer.

Ambulatory electrogastrography in patients with sclerodermia, delayed gastric emptying, dyspepsia, and irritable bowel syndrome. Is there any clinical relevance?

Background: Changes in electrogastrographic parameters are described in patients with irritable bowel syndrome, sclerodermia, dyspepsia, and delayed gastric emptying in static measurements. However, no information is available about changes in ambulatory measurements. The objective of this study was to find parameters that discriminate between these diseases using cutaneous 24-h-electrogastrography. Methods: Cutaneous 24-h electrogastrography (EGG) measurements were taken from 20 patients with dyspepsia, 10 patients with systemic sclerosis (sclerodermia, SSc), 7 patients with irritable bowel syndrome (IBS), 7 patients with delayed gastric emptying, and 10 healthy volunteers. Measurements were made using a DIGITRAPPER EGG (Synectics Medical Inc., Stockholm, Sweden) and the accompanying computerized data analysis package (ElectroGastroGram Version 6.30, Gastrosoft Inc., Synectics Medical Inc., Stockholm, Sweden). Frequency and power were compared pre- and postprandially, as well as during the entire day of measurement. Results: The 24-h measurements in healthy volunteers revealed 45.00%+/-12.12% normal values (2.4-3.7 cpm), 30.10%+/-7.15% bradygastric values (<2.4 cpm), and 24.20%+/-7.76% tachygastric values (>3.7 cpm). There was no significant change in frequency between rest and motion, but there was a significant increase in power (P<0.05). There was significantly more bradygastria in patients with dyspepsia periprandially as well as after 24 h (P<0.01) than in healthy volunteers. The mean power of patients with dyspepsia was significantly higher than that of patients with IBS (P<0.05). Conclusion: Cutaneous 24-h-EGG may be used as an additional means of differentiating between dyspepsia and IBS.

Increased biliary secretion of cysteinyl-leukotrienes in human bile duct obstruction.

BACKGROUND/AIMS: The pathophysiological role of leukotrienes in liver disease is not well understood. Redistribution or enhanced formation in cholestatic states may result in increased hepatic concentrations that are expected to contribute to liver injury. To disclose the potential role of cysteinyl-leukotrienes in chronic liver diseases, we studied biliary and urinary secretion in the model situation of relief of bile duct obstruction. METHODS: Concentrations of cysteinyl-leukotrienes were determined in bile and urine of patients with extrahepatic biliary obstruction in the course of therapeutic decompression by endoscopic or transhepatic techniques. Leukotrienes were measured by radioimmunoassay after HPLC separation. Concentrations of bile acids in bile and serum were measured for comparison. RESULTS: Bile collected 2 h after decompression contained high concentrations of leukotrienes (57.5 +/- 22 microM). Biliary secretion decreased over 24 h reaching equilibrium values after 48-72 h (2.8 +/- 1.7 mM and 6.4 +/- 6.6 microM, respectively). Total bile acid concentration in serum followed a similar time course. In contrast, biliary bile acid concentration showed high interindividual variations. Bile contained all leukotriene C4, D4, E4 and NAc-LTE4, but LTC4 was predominant. Urinary leukotriene secretion in cholestasis (199.7 pmol/mmol creatinine) was less than 7% of maximal biliary secretion. It further decreased to 116.4 pmol/mmol creatinine within 72 h. Urine also contained all species of cysteinyl-leukotrienes, but the relative amounts of LTE4 and NAc-LTE4 were higher than in bile. CONCLUSIONS: Formation of cysteinyl-leukotrienes is increased in obstructive jaundice resulting in increased urinary excretion before and both biliary and urinary excretion after relief of the obstruction. Predominance of LTC4 suggests that the secreted leukotrienes are newly formed. Increased synthesis and retention of hepatic cysteinyl-leukotrienes may contribute to hepatic and extrahepatic consequences of cholestasis.

[Experiences with the 14C-aminopyrine breath test in liver cirrhosis and under the effect of sodium diclofenac (Voltaren)]. / Erfahrungen mit dem 14C-Aminopyrin-Atemtest bei Leberzirrhose und unter dem Einfluss von Diclofenac-Natrium (Voltaren).

The 14C-aminopyrine breath test is a simple procedure for the non-invasive determination of the microsomal function of the liver. After the oral administration of a tracer dose of 2 microCi (74 kBq) of 14C-aminopyrine the 14CO2 activity of the expired breath air is determined in hourly intervals. There is a close correlation between its decrease and the elimination of aminopyrine from the plasma. Both the elimination constant of 14CO2 (Kbreath) and the maximal specific 14CO2 activity are useful quantitative parameters of the test. They allow conclusions as to the hepatic demethylation capacity. Both parameters were significantly lower in 15 patients with liver cirrhosis than in 12 control patients. The non-steroidal anti-inflammatory drug diclofenacsodium (Voltaren) did not significantly influence the demethylation of 14C-aminopyrine in 5 patients with rheumatic diseases and in 2 healthy probands. Further experiences with the breath test are necessary, especially with respect to its suitability for prospective investigations.

[Results of coloscopic polypectomy in respect of the dignity (author's transl)]. / Ergebnisse der koloskopischen Polypektomie im Hinblick auf die Dignität.

The commonest type of polyps in the large intestine in our series of 506 polypectomies in 262 patients were adenomas (64%) especially tubular adenomas. Severe epithelial atypia being present in 11% of all adenomas and it was three times more discovered in villous adenomas than in tubular forms and with increasing adenomas size. Because severe epithelial atypia could be observed in polyps with diameters less than 5 mm it should be demanded to remove each polyp for an exact histological examination independent of his size. Single forceps biopsies of polyps do not allow the estimation of their further development in view of malignancy.

[Causes of gastrointestinal hemorrhages in chronic liver diseases]. / Ursachen gastrointestinaler Blutungen bei chronischen Leberkrankheiten.

356 patients with chronic liver diseases hospitalized in our clinic during the period from January 1, 1981, to December 12, 1983, were enrolled in a retrospective study. Of them 55 had been admitted for acute gastrointestinal hemorrhage. It appears that gastroscopy is the only method allowing to localize the origin of the bleeding with high certainty. Bleedings from varices (45%) and ulcers or erosions (22%) were seen most frequently. With regard to case history, clinic, paraclinic and prognosis, no significant differences were found between these various origins of the hemorrhages. Also it is remarkable that all bleedings occur with higher frequency in portal hypertension.

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.

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.

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.

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.