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Aim The applicability of ultrasound for diagnosing mediastinal diseases is limited by the surrounding thorax containing air and bone, permitting only restricted echo windows. Transoesophageal endoscopic ultrasound circumvents this problem and provides good visualisation of nearly all parts of the mediastinum. We evaluated the value of endoscopic ultrasonography for mediastinal staging of Hodgkin's and non-Hodgkin lymphoma patients. Patients and methods From August 1994 to July 1995 36 Hodgkin's and non-Hodgkin lymphoma patients underwent clinical staging and were endosonographically examined for mediastinal involvement. CT in the spiral technique was used as the reference. Results In assessing mediastinal involvement, endoscopic ultrasound revealed a sensitivity of 96% and a specificity of 75%. There were limitations in the right paratracheal region and the area lateral to the aortic arch. Conclusion Endoscopic ultrasound is a highly valuable imaging procedure for diagnosing mediastinal spread of malignant lymphomas and has interesting potentials in assessing the clinical course during therapy.

Immunological parameters and histocompatibility antigens (HLA) were determined in seven patients with non-bacterial cholangitis. Four patients had pericholangitis and ulcerative colitis, three had primary sclerosing cholangitis, one of these with ulcerative colitis. All 7 patients had antinuclear antibodies; however, there were no antibodies against DNA, against mitochondria or liver membrane antigens. One patient had low-titre rheuma factors. Immunoglobulins G, A and M and complement components C3 and C4 were mostly in the normal range. HLA constellation was positive for B8 in 6 patients. These were male patients with disease manifestations between the 12th and 45th year of life. The results support the concept that pericholangitis and primary sclerosing cholangitis with or without ulcerative colitis are related hepatological disease entities with an immunological pathogenesis and an underlying genetical determination.

An epidemic of Q fever in Berlin affected at least 80 patients (45 females, 35 males; age range 1-75 years). Sheep were identified as the focus of infection: they had been brought to a veterinary clinic because of nonspecific symptoms. The peak incidence of the infection was in April and May, 1992. Most of the patients were staff or students at the veterinary clinic. This is the most northern and, at the same time largest, Q fever epidemic recorded in Germany over the last 28 years. The complement fixation reaction (CFR) was not helpful diagnostically in the acute stage of the disease as it remained negative in the first 14 days (CFR < or = 1:5). Most of the patients had sudden fever to over 40 degrees C, severe headache and dry cough. Pulmonary infiltrates were seen in the chest radiograph of 8 of the 10 patients presented in this contribution. Auscultation was largely negative. Two patients had signs of hepatic involvement (GPT as high as 71 U/l). The drug of choice was doxycycline at a dosage of 200 mg twice daily for 14 days.

Die Zoliakie weist verschiedene Verlaufsformen auf und ist in ihrem klinischen Erscheinungsbild sehr heterogen. Dies erfordert eine differenzierte Therapie und Betreuung der Patienten. Aus den Reihen des arztlichen Beirates der Deutschen Zoliakie-Gesellschaft wurde eine Arbeitsgruppe gebildet, um die Bezeichnungen der verschiedenen Verlaufsformen der Zoliakie, die bislang uneinheitlich benutzt wurden, naher zu definieren. Durch die konsequente Beachtung und Anwendung der unterschiedlichen Definitionen der Zoliakie konnen Unsicherheiten beim behandelnden Arzt vermieden und hierdurch eine Vereinheitlichung und Verbesserung der Patientenversorgung erreicht werden.

Celiac disease may have different manifestations and the clinical course can be very heterogeneous. Thus, management and treatment of celiac disease can be difficult and therefore requires individual patient care. In this article an expert group from the German Society for Celiac Disease (Deutsche Zoliakie-Gesellschaft) defines the different manifestations of celiac disease. In the past these definitions were often used differently. The consequent usage of these definitions may diminish uncertainties in clinical practice and lead to a more standardized management of the disease which is likely to improve patient care.

* Der Beitrag »Therapie der gastroosophagealen Refluxkrankheiten« erscheint im folgenden Heft (Nr. 43)

The case described concerns a 68-year-old male patient, who received intravesical BCG instillations for non-resectable urothelial carcinoma (stage pT1, G2). After the third instillation, which was complicated by hematuria during catheterization, he had a high temperature, dyspnoea, a weight-loss of 15 kg and critical recurrent hypotension for 3 weeks. On admission to the clinic he presented with high serum liver enzymes and pancytopenia. The suspected diagnosis of BCG sepsis was confirmed by the detection of typical granulomas in liver and bone marrow histology. After initiation of tuberculostatic therapy, the patient's condition improved and laboratory results returned to normal. This case shows the potential of a life-threatening systemic side effect after intravesical BCG instillation.

Background: Our aim was to study the influence of psychotherapy in addition to a standardized corticosteroid treatment on the somatic and psychosocial course of Crohn's disease. Methods: In a prospective, randomized multicenter study 108 of 488 patients received either drug treatment or, in the intervention group, additionally psychotherapy in the first half of the 2-year follow-up period. Results: Eighty-four patients (77.8%) completed the somatic and 81 (75%) the psychosocial follow-up. Twenty-three per cent of the control group and 30% of the psychotherapy group showed episode-free courses; 29% and 17%, respectively, underwent surgery due to failure of drug treatment. The main analysis, which was based on subranking by number, duration, and severity of relapses, failed to show significant differences between the two groups (P = 0.125). The same result was obtained for the psychosocial status after 1 year in the main target criteria depression, anxiety, psychosocio-communicative status, and quality of l...

Duodenal gastrinomas in childhood are extremely rare and often missed at first medical consultation. We report on a 7-year-old child with sporadic gastrinoma of primary localisation in the distal duodenum. Small metastases in the liver and regional nodes were detected pre-operatively by somatostatin receptor scintigraphy (SRS) but not by other conventional imaging procedures. Diagnostic procedures include pre-operative SRS, endoscopic ultrasound and intra-operative endoscopic transillumination.Gastrinomas are rare abdominal tumours in childhood. Pre-operative tumour-specific diagnosis is possible by 111indium pentreotide SRS.

Einleitung: Die Diagnostik mediastinaler Erkrankungen erfolgt im wesentlichen durch CT und Magnetresonanztomographie (MRT). Die Einsatzmoglichkeiten des Ultraschalls sind durch den umgebenden luft- und knochenhaltigen Thorax, der nur begrenzte Schallfenster zulast, eingeschrankt. Der transosophageal durchgefuhrte endoskopische Ultraschall umgeht dieses Problem und erlaubt, die pratrachealen Bereiche ausgenommen, einen guten Uberblick uber das Mediastinum. Patienten und Methoden: Wir berichten uber die Ergebnisse einer retrospektiven Auswertung bei 38 Patienten mit pathologischen mediastinalen Befunden, die zwischen 1988 und 1993 mittels endoskopischem Ultraschall untersucht wurden. Die Diagnosestellung erfolgte durch bildgebende Verfahren und/oder histologisch. Ergebnisse: Bei 38 Patienten wurden folgende Mediastinalveranderungen diagnostiziert: A. lusoria (n = 3), rechtsdeszendierende Aorta (n = 1), Aortenaneurysmen (n = 6), Zysten (n = 4), retrosternale Schilddrusenanteile (n = 3), Lymphknotentuberkulose (n = 1), Hodgkin- bzw. Non-Hodgkin-Lymphome (n = 11), Lymphknotenbeteiligung bei Bronchialkarzinom (n = 8), mediastinales Fibrosarkom (n = 1). Insgesamt konnten 37/38 pathologische Befunde endosonographisch dargestellt werden. Schlusfolgerungen: Die Ergebnisse an diesem kleinen Kollektiv von Patienten mit pathologischen Mediastinalbefunden zeigen, das der endoskopische Ultraschall zusatzliche Informationen zu radiologischen Verfahren liefern kann. Zur Evaluierung ihres Stellenwerts im Vergleich zu den etablierten bildgebenden Verfahren ist eine vergleichende, prospektive Untersuchung gerechtfertigt und notwendig.

Neuroendocrine tumors of the gastroenteropancreatic system present not only a diagnostic but also a therapeutic challenge. In case of limited neuroendocrine tumor disease curative surgery is the goal

Neuroendocrine tumors of the gastroenteropancreatic system present both a diagnostic and therapeutic challenge. Even in a patient presenting with a clinical hypersecretion syndrome such as the carcinoid syndrome, the Zollinger-Ellison syndrome or the hypoglycemia syndrome the primary tumor is often difficult to localize. Recently, tumor imaging has been improved by two new powerful techniques, the endosonography and the somatostatin-receptor scintigraphy. In addition, the new arterial secretin or calcium injection tests may guide surgery in patients with gastrinoma or insulinoma, respectively. The recently introduced positron emission tomography with nC-5-hydroxytryptophan can provide information about biochemical and metabolic changes in neuroendocrine tumors. Patients with the hereditary form of neuroendocrine tumor disease of the foregut suffer from the multiple endocrine neoplasia type 1 syndrome. The genetic defect of this autosomal dominant disease has been assigned to chromosomal region 11 q13. Current investigations aim to detect the multiple endocrine neoplasia 1 gene and thus to allow early diagnosis of hereditary neuroendocrine tumor disease of the foregut.

Celiac disease is characterized by mucosal changes in the small intestine, ranging from increased numbers of intraepithelial lymphocytes to complete villus effacement with various signs of malabsorption (1,2). Celiac disease is diagnosed by the demonstration of an altered intestinal mucosa in a jejunal biopsy specimen (3). Celiac disease patients invariably have antibodies directed against gliadin and endomysium, a structural component of the extracellular matrix: both antibodies disappear under a gluten-free diet. Therefore, these antibodies are useful tools for diagnosis, and in the dietary control of coeliac disease (3-7). Serum IgA antibodies against endomysial antibodies (EMAs) are especially considered to be sensitive and highly specific markers for celiac disease (8)(9). Previously, EMAs were detected by indirect immunofluorescence on tissue slides of monkey esophagus or human umbilical cord (10-12).

Summary The decisive aspect of Yersinia enterocolitica virulence in vivo is the ability of the plasmid-bearing bacteria to resist the immune response within the host tissue. The expression of plasmid-mediated virulence proteins was investigated in the intestinal lumen and in the Peyer's patches of infected mice. Three novel plasmid-mediated outer-membrane proteins have been identified with antisera raised against bacteria grown in vivo. When the bacteria were grown in the intestinal lumen, all plasmid-coded proteins known to be expressed in vitro, except the 26-Kda protein were expressed. Additionally, a novel outer-membrane protein of 23 Kda was synthesised. After penetration into the Peyer's patches, two further proteins of 240 and 210 Kda were expressed. None of these three proteins was detected in the outer membrane of bacteria grown in vitro. By contrast, plasmid-coded released proteins, which are abundantly synthesised in Ca2+-deficient media in vitro, were not detectable in the ileal lumen nor in the tissue of infected Peyer's patches, which suggests that they are not required for Y. enterocolitica pathogenesis.

During intravariceal sclerotherapy of esophageal varices with polidocanol in 32 patients with portal hypertension due to liver cirrhosis of various etiologies, endosonographic assessment of both esophageal and gastric intramural vessels was carried out in order to evaluate the usefulness of endosonography in the follow-up of the variceal status. In all cases endosonography demonstrated esophageal and gastric varices; in contrast, only five cases of gastric varices could be demonstrated by endoscopy. Furthermore, different stages of variceal obliteration following sclerotherapy could be demonstrated by means of endosonography, and it was possible to identify incomplete obliteration in about one-third of the patients in whom inadequate sclerotherapy was suspected endoscopically. In addition, the status of gastric varices during sclerotherapy was demonstrated by means of endosonography. Only in cases of adequate sclerotherapy of esophageal varices, as assessed by both endoscopic and endosonographic criteria, were gastric varices plugged. On the basis of these findings endosonography would appear to be a useful technique for the diagnosis and follow-up of esophageal and gastric varices during intravariceal sclerotherapy.

In this study we investigated the effects of steroid hormones on glandular kallikrein gene expression in the rat pancreatic acinar cell line AR42J. Using a cloned complementary DNA probe and a polyclonal antibody we demonstrated expression of a true glandular kallikrein gene and protein in AR42J cells by Western and Northern blot analysis. Dexamethasone resulted in a time-dependent parallel decrease of kallikrein messenger RNA and protein with a maximum at 12 and 72 h (30 +/- 10 and 8 +/- 0.5% of control, respectively, P less than 0.05, n = 6). In contrast, dexamethasone stimulated gene expression of two other serine proteases, chymotrypsin and trypsin, approximately 3 to 4-fold. The decrease of kallikrein concentration was dose dependent with half-maximal effects at 5 x 10(-8) M and maximal effects at 10(-7) M dexamethasone (23 +/- 6% of control, n = 3). The glucocorticoid antagonist RU 38486 blocked the glucocorticoid-induced decrease in cellular kallikrein content in a dose-dependent manner. Complete inhibition was observed at equimolar doses of dexamethasone and the antagonist. The inhibitory effect of dexamethasone was completely reversible after hormone withdrawal for 24 h. Neither estrogen, progesterone, testosterone, or aldosterone had significant effects on kallikrein expression. These data suggest that down-regulation of pancreatic kallikrein gene expression occurs selectively in response to glucocorticoids at a pretranslational level, mediated most likely by the glucocorticoid receptor.

Intracavitary application of ultrasound was first performed for diagnostic purposes in 1967; since that time, it has been more and more widely used. As far as the gastrointestinal tract is concerned, endoscopically controlled ultrasonic probes provide visualization of the various layers of the intestinal wall. It is therefore possible to describe lesions of the esophagus, stomach, and the rectum with regard to their nature and depth of infiltration. Furthermore, periesophageal and perigastric organs can be visualized. It has become evident that endosonography is particularly important for pretherapeutic staging of tumors of the esophagus, stomach, and rectum. Here prospective comparative studies confirm the superiority of this new diagnostic procedure when compared to the methods available to date.

The Ag recognized by the mAb HML-1 is expressed on more than 90% of human intestinal intraepithelial lymphocytes, whereas in other lymphoid tissues it is rarely or not expressed. In the present study, we have investigated the percentage of HML-1-positive cells in the human intestinal lamina propria and the coexpression of HML-1 with different T cell subset markers. In addition, we studied the inducibility of HML-1 on PBL which normally are HML-1-negative. Flow cytometric analysis of isolated intestinal lamina propria lymphocytes (LPL) showed that about 40% of the cells expressed HML-1, the majority belonging to the CD8-positive subpopulation. Virtually all LPL expressed CD45RO, whereas the percentage of CD29-positive cells was only about 50%, similar to PBL. There were only few cells expressing CD45RA or Leu-8 in the lamina propria. HML-1-positive cells were almost exclusively CD45RA-negative, but were found in both the CD29-positive and the CD29-negative subpopulation of LPL. In vitro stimulation of PBL showed that the expression of HML-1 was inducible on T cells by mitogens, phorbolester, Ag, and rIL-2. Expression of HML-1 was induced with a different time course and with differences in the response to the investigated stimuli compared with CD25. Activated HML-1-positive PBL were also predominantly CD45RA-negative. The findings show that HML-1 is an Ag, which is expressed in vivo on a specific subset of previously activated T cells in the unique environment of the intestinal mucosa, and which can be induced in vitro by different activation signals on PBL.

Celiac disease may have different manifestations and the clinical course can be very heterogeneous. Thus, management and treatment of celiac disease can be difficult and therefore requires individual patient care. In this article an expert group from the German Society for Celiac Disease (Deutsche Zöliakie-Gesellschaft) defines the different manifestations of celiac disease. In the past these definitions were often used differently. The consequent usage of these definitions may diminish uncertainties in clinical practice and lead to a more standardized management of the disease which is likely to improve patient care.

Prognosis of advanced, unresectable pancreatic adenocarcinoma remains dismal and has not significantly improved over the past 20 years. In a broad panel of preclinical experimental settings we have therefore evaluated the effects of retinoids on human pancreatic carcinoma cells in vitro and in vivo. We found that retinoid treatment results in inhibition of growth, induction of cellular differentiation and decreased adhesion to certain components of the extracellular matrix, all features compatible with a "less malignant" phenotype. Furthermore, retinoids act synergistically antiproliferative when combined with interferon-alpha. Using transient and stable genetic transfer studies we were able to identify two retinoid receptor subtypes responsible for mediating the growth inhibitory effects as well as retinoid sensitivity. In addition we observed a crucial functional interplay between the retinoid signalling pathway and the expression of a distinct protein kinase C isoenzyme, which determines the direction of the growth regulatory effects of retinoids. Based on these encouraging preclinical results we initiated a phase II clinical trial in which patients with advanced pancreatic carcinoma were treated with retinoic acid in combination with interferon-alpha. This therapeutic regimen was well tolerated and resulted in prolonged stable disease in approximately two thirds of the patients. In summary, these studies suggest that retinoids might be beneficial in the treatment of advanced pancreatic carcinoma patients based on their pleiotropic effects on tumor cell biology.

BACKGROUND—The molecular mechanisms underlying the differential sensitivity of human colon carcinoma cells to retinoid mediated growth inhibition are poorly understood. AIM—To identify the intracellular mechanisms responsible for resistance against retinoid mediated growth inhibition in human colon carcinoma cells. METHODS—Anchorage independent growth of the human colon carcinoma cell lines HT29 and LoVo was determined by a human tumour clonogenic assay. Retinoid receptor expression was evaluated by reverse transcription polymerase chain reaction and northern blotting. Retinoid mediated transactivation was assessed by transient transfection of a pTK::βREx2-luc reporter construct. Retinoid receptor overexpression was achieved by selecting stably transfected cell clones. RESULTS—Retinoid treatment resulted in profound dose dependent growth inhibition in HT29 cells, while LoVo cells were unaffected. The two cell lines express identical patterns of nuclear retinoid receptor mRNA transcripts. However, on retinoid treatment, retinoic acid receptor β gene expression was upregulated only in retinoid sensitive HT29 cells, but not in retinoid resistant LoVo cells. In accordance, stable overexpression of retinoic acid receptor β but not α or γ conferred retinoid mediated growth inhibition on LoVo cells. CONCLUSION—Induction of retinoic acid receptor β expression is required and sufficent to confer retinoid mediated growth inhibition on human colon carcinoma cells. Keywords: colon cancer; retinoic acid; retinoic acid receptor

This study was undertaken to clarify whether immunohistological detection of tenascin (TN), an extracellular matrix glycoprotein that is expressed during stromal remodelling, may allow a more precise diagnosis of collagenous colitis.We studied multiple colorectal biopsies specimens from 15 patients with clinically suspected collagenous colitis for TN expression by using a monoclonal antibody. Biopsies from further 15 patients without symptoms and signs of collagenous colitis served as controls. In seven of the 15 cases with clinically suspected collagenous colitis a prominent and selective subepithelial tenascin expression was identified. The TN expression pattern closely correlated with the conventional detection of a subepithelial collagen band diagnostic of collagenous colitis. The immunohistological labelling for TN allowed a quicker and more precise measurement of the thickness of the diagnostic collagen deposits than conventional staining. By this approach one further case could be reclassified as collagenous colitis.Our data show that immunohistological detection of TN allows a more correct and easy diagnosis of collagenous colitis.

Our aim was to study the influence of psychotherapy in addition to a standardized corticosteroid treatment on the somatic and psychosocial course of Crohn's disease.In a prospective, randomized multicenter study 108 of 488 patients received either drug treatment or, in the intervention group, additionally psychotherapy in the first half of the 2-year follow-up period.Eighty-four patients (77.8%) completed the somatic and 81 (75%) the psychosocial follow-up. Twenty-three per cent of the control group and 30% of the psychotherapy group showed episode-free courses; 29% and 17%, respectively, underwent surgery due to failure of drug treatment. The main analysis, which was based on subranking by number, duration, and severity of relapses, failed to show significant differences between the two groups (P = 0.125). The same result was obtained for the psychosocial status after 1 year in the main target criteria depression, anxiety, psychosocio-communicative status, and quality of life.The confirmatory analysis did not prove significantly better courses after additional psychotherapy. There was a tendency towards fewer operations.

Advanced unresectable pancreatic adenocarcinoma has a dismal prognosis. The authors previously have shown that retinoic acid (RA) and interferon-alpha (IFN-alpha) inhibit growth and induce differentiation in human pancreatic carcinoma cells in vitro and in vivo. The purpose of this trial was to examine the feasibility and tolerability of a combination therapy of 13-cis RA and IFN-alpha in patients with advanced unresectable pancreatic carcinoma.Twenty-two patients (median age, 62 years) with histologically confirmed, unresectable pancreatic adenocarcinoma classified as International Union Against Cancer Stage III (5 patients) or IV (17 patients) were included. Patients received 1 mg/kg body weight 13-cis RA orally and 6 million IU IFN-alpha subcutaneously daily. Restaging by ultrasound, computed tomography scan, and chest X-ray was performed every 2 months.No complete remission and 1 partial remission (PR) (4.5%) were observed. Fourteen patients (63.6%) demonstrated stable disease with a median duration of 5.0 months (range, 2.3-17.7+ months). Toxicity mainly was related to IFN-alpha and predominantly was hematologic (no toxicity was World Health Organization [WHO] Grade 4 and 13.6% were WHO Grade 3). Nonhematologic toxicities did not exceed Grade 2 (skin and oral mucosa) and mainly were related to 13-cis RA. The median survival of the patients with Stage III disease was 8.7 months (range, 6.8-23.9+ months) and was 7.4 months for patients with Stage IV disease (range, 0.9-19.2+ months), resulting in a median overall survival of 7.7 months (range, 0.9-23.9+ months).Combination therapy with 13-cis RA and IFN-alpha is feasible and well tolerated in patients with advanced pancreatic carcinoma. Based on the median survival rates observed in this study this combination should be investigated further in Phase III trials.

We compared the efficacy of three dual and two triple therapies for eradication of Helicobacter pylori (HP), and evaluated the influence of smoking and omeprazole pretreatment on HP eradication. 220 patients with proven HP infection (histology and 13C-urea breath test [UBT]) were randomly allocated to one of the following regimes: BMT (bismuth subsalicylate 600 mg t. i. d. for 28 days, metronidazole 400 mg t. i. d. and tetracycline 500 mg q. i. d. for ten days). OA (omeprazole 40 mg o. d. and amoxicillin 750 mq q. i. d. for 14 days), OC (omeprazole 40 mg o. d. and clarithromycin 500 mg b. i. d. for 14 days), OT (omeprazole 40 mg o. d. and tetracycline 500 mg q. i. d. for 14 days), OMC (omeprazole 40 mg o. d., metroinidazole 400 mg t. i. d. and clarithromycin 250 mg b. i. d. for seven days). Eradication was defined as negative UBT six weeks after completion of the therapy. In an "all-patients-treated" ("per-protocol") analysis, the eradication rates were: BMT, 91% (93%); OA, 84% (90%); OC, 74% (74%); OT, 24% (24%); and OMC, 90% (93%). Smoking impaired the success of OA and OT (p0.05), but the efficacy of the triple regimens was not affected. Omeprazole pretreatment did not influence eradication rates. Thus, highest eradication rates were achieved with the two triple therapies tested. However, OA, given at a daily antibiotic dose of 3 g amoxicillin for 14 d, was also highly effective. After failure of triple therapy, OA was successful in seven of ten patients (70%). The efficacy of OC was lower than that of the triple therapies (p0.05). In conclusion, metronidazole- and clarithromycin-based triple therapies are highly effective first line therapies. OA, given at a dose of 3 g per day over 14 days, should be considered as a possible second line therapy, e.g. in retherapy after failed triple therapy.

Inflammatory bowel disease (IBD) and HIV infection can cause diarrhoea which is accompanied by elevated cytokine levels. To elucidate a pathogenic role of cytokines, their effect on ion secretion was studied in human distal colon using the Ussing technique. Interluekin 1beta (IL-1beta) dose dependently increased short-circuit current (ISC). An ISC maximum of 2.5+/-0.3 micromol. h-1.cm-2 was reached at 20 ng/ml within 43+/-4 min. 22Na+ and 36Cl- fluxes were not altered and residual flux increased by 2.4+/-1.0 micromol.h-1.cm-2 indicating that the IL-1beta-induced ISC is based on electrogenic bicarbonate secretion. IL-1beta had no effect on HT-29/B6 epithlial monolayers suggesting that IL-1beta does not act directly on the epithelium. Furthermore, in human colon the effect was not attenuated by removal of the submucosa (total stripping) pointing to a mediation step via subepithlial cells in the lamina propria. While tetrodotoxin and the 5-lipoxygenase inhibitor ICI-230487 had no effect, indomethacin completely blocked IL-1beta action. Prostaglandin determination by RIA revealed an increased production of PGE2. At half maximum effective concentrations an additive action of tumour necrosis factor alpha (TNF-alpha) could be demonstrated on IL-1beta-induced secretion. Interferon alpha (IFN-alpha), IFN-gamma, IL-6, and IL-8 had no seretory effect in human distal colon. None of the investigated cytokines altered the intestinal barrier function. By their secretory effects IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6, and IL-8, may contribute to diarrhoea in IBD and AIDS.

Previous studies have shown that self-antigens overexpressed in malignant tissue can provide a basis for a tumor-specific immune response. The mucin MUC2 is strongly overexpressed in all mucinous tumors of colon, breast, ovary and pancreas. In the corresponding normal tissue it is either not expressed (breast, ovary, pancreas) or it is expressed at considerably lower levels than in the mucinous tumors (colon). We therefore investigated whether the MUC2 molecule comprises HLA-A2-binding epitopes recognized by human cytotoxic T cells. Four MUC2 peptides with high affinity and stable binding to HLA-A2 were identified. Those peptides and additionally 3 peptides with moderate binding to HLA-A2 were loaded onto dendritic cells, which were used for stimulation of autologous T cells from healthy donors. Two MUC2 peptides, which belonged to the group of stable binders, induced specific cytotoxic T-cell lines. Target cells loaded with these peptides were strongly lysed in a concentration-dependent and HLA-A2-restricted manner. Our data show that the tumor-associated mucin MUC2 has potential as a target antigen for cytotoxic T cells in patients with mucinous carcinomas.

Esophageal intramural pseudodiverticulosis is a rare benign condition with the cardinal symptom of dysphagia mostly due to inflammatory strictures. The disease frequently develops in connection with alcohol abuse and esophageal reflux, candidiasis or motility disorders. Characteristic is the radiological visualization of intramural saccular contrast accumulations. We report on five patients with esophageal pseudodiverticulosis endoscopically diagnosed at our hospital within a period of five years. Four of these patients underwent extensive investigations for additional esophageal conditions: Histological/cytological examinations, manometry, pH-metry and endoscopic ultrasonography. These four patients had a pathological reflux with marked esophagitis and inflammatory strictures. We achieved long-lasting therapeutic results with complete relief by bougienage and reflux therapy with additional candidiasis treatment in two and motility treatment in one patient each. The detailed discussion deals with the clinical aspects, characteristics, therapy and pathogenesis.

Mucinous carcinomas of the colorectum have been reported to overexpress the intestinal mucin MUC2. The purpose of this study was to determine whether this alteration is shared by mucinous tumours of the ovary, breast, and pancreas. A total of 40 breast carcinomas (22 of mucinous and 18 of ductal invasive type), 39 ovarian adenocarcinomas (16 mucinous, 23 serous), 47 colorectal carcinomas (25 mucinous and 22 non-mucinous), and 41 pancreatic adenocarcinomas (14 mucinous, 27 non-mucinous) were investigated by immunohistochemistry with the anti-MUC2 monoclonal antibody 4F1 and the expression pattern was ranked. MUC2 mucin is expressed in the normal colonic epithelium; in the normal epithelium of the breast, ovary, and pancreas, it was not detectable by immunohistochemistry or by reverse transcriptase-polymerase chain reaction (RT-PCR). In agreement with previous reports, the colonic mucinous carcinomas differed significantly from the non-mucinous carcinomas by strong MUC2 expression. In all mucinous carcinomas of the ovary, breast, and pancreas, de novo expression of the MUC2 gene was observed, which differentiated mucinous and non-mucinous carcinomas of these tissues (P0.001). The overexpression or ectopic expression of the MUC2 gene exhibited by mucinous carcinomas of four organs indicates a common genetic lesion associated with the mucinous tumour phenotype.

Two factors potentially determining the consistent overexpression of sialyl-Le(x) antigen in colon carcinoma and metastases were investigated: (i) the expression of the mucins MUC1 and MUC2, known to carry sialyl-Le(x), by Northern blotting; (ii) the extent of sialic acid O-acetylation, by Western blotting and HPLC. RNA and sialyl-Le(x)-positive mucins were purified from normal colonic mucosa (N), primary carcinomas (T) and their liver metastases (M). Northern blots showed that mRNA expression both of MUC1 and of MUC2 decreases during the progression of the disease, and is lowest in metastatic tissue. The expression of mucin-bound sialyl-Le(x) increased strongly from N to T and, to a lesser extent, to M. After alkali treatment of the mucins these differences disappeared, indicating that the total amount of mucin-bound sialyl-Le(x) is the same in the 3 types of tissues. The O-acetylation of mucin-bound sialyl-Le(x) gradually decreased from N to M. HPLC analysis showed that in N about 70%, in T 45% and in M only 20% of mucin-bound sialic acids are O-acetylated. Thus, the increase of sialyl-Le(x) detectable during colon-carcinoma progression is due to diminished O-acetylation and not to increased expression of mucin protein cores. The decrease of O-acetylation is therefore the primary chemical alteration contributing to colon carcinoma-associated overexpression of sialyl-Le(x).

Intestinal T-cell lymphoma (ITCL) represents a subgroup of peripheral T-cell lymphomas which is thought to arise from alpha beta intraepithelial T-lymphocytes. Since these lymphocytes may contain cytotoxic molecules, the question of whether this also holds true for ITCL arises. Twenty ITCL cases were examined for the presence of granzyme B, perforin, and T-cell-restricted intracellular antigen (TIA-1)/granule membrane protein of 17 kD (GMP-17). Two molecules with restricted expression in cytotoxic cells, granzyme B and perforin, were detected by immunocytochemistry and by in situ hybridization with an isotopically labelled RNA probe, respectively. Immunocytochemistry was also performed with the antibody 2G9, which recognizes two molecules, one expressed by cytotoxic cells (TIA-1) and the other found in granulocytes and cytotoxic cells (GMP-17). Granzyme B, TIA-1/GMP-17, and perforin were found in the neoplastic cells of 16/19 cases, 19/20 cases, and 16/17 cases, respectively, of ITCL, but not in the tumour cells of the control group, which consisted of intestinal B-cell lymphomas (five cases) and CD8-negative peripheral nodal T-cell lymphomas (six cases). At least one of these molecules was expressed in the tumour cells of all ITCL cases. 2G9 proved to be the most sensitive immunohistological marker, since reactivity with this antibody was not only observed in the highest number of cases, but also found in high numbers of neoplastic cells in positive cases. In conclusion, ITCL appears to show cytotoxic differentiation in all cases. In conjunction with immunophenotypic and genotypic data, our results support a uniform derivation of this tumour from intraepithelial alpha beta cytotoxic T-lymphocytes.

The applicability of ultrasound for diagnosing mediastinal diseases is limited by the surrounding thorax containing air and bone, permitting only restricted echo windows. Transoesophageal endoscopic ultrasound circumvents this problem and provides good visualisation of nearly all parts of the mediastinum. We evaluated the value of endoscopic ultrasonography for mediastinal staging of Hodgkin's and non-Hodgkin lymphoma patients.From August 1994 to July 1995 36 Hodgkin's and non-Hodgkin lymphoma patients underwent clinical staging and were endosonographically examined for mediastinal involvement. CT in the spiral technique was used as the reference.In assessing mediastinal involvement, endoscopic ultrasound revealed a sensitivity of 96% and a specificity of 75%. There were limitations in the right paratracheal region and the area lateral to the aortic arch.Endoscopic ultrasound is a highly valuable imaging procedure for diagnosing mediastinal spread of malignant lymphomas and has interesting potentials in assessing the clinical course during therapy.

Mediastinal diseases are mostly diagnosed by CT and MRI. The applicability of ultrasound is limited by the surrounding air- and bone-containing thorax, which permits only restricted echo windows. Transesophageal endoscopic ultrasonography circumvents this problem and ensures visualization of parts of the mediastinum.We report our results in 38 patients with pathological mediastinal findings who were examined by endoscopic ultrasound between 1988 and 1993. The diagnoses were established by imaging and/or histological procedures.The following mediastinal diseases were diagnosed in 38 patients: aberrant right subclavian artery (n = 3), right aortic arch (n = 1), aortic aneurysm (n = 6), cysts (n = 4), retrosternal struma (n = 3), mediastinal lymph node tuberculosis (n = 1), Hodgkin's/non-Hodgkin's lymphomas (n = 11), lymph node involvement in bronchogenic carcinoma (n = 8), mediastinal inflammatory fibrosarcoma (n = 1). Altogether, 37/38 pathological findings were demonstrated endosonographically.The results in this small group of patients with pathological mediastinal findings show that endoscopic ultrasound can give additional information to conventional imaging methods. A prospective comparative study is necessary to evaluate this procedure in comparison to the established imaging techniques.

Bei der chronischen intestinalen Pseudoobstruktion handelt es sich um ein klinisches Syndrom, das durch eine ineffektive Propulsion verursacht wird und durch Zeichen der Obstruktion bei Fehlen einer okkludierenden Lasion charakterisiert ist. Die chronisch intestinale Pseudoobstruktion kann sekundar bei systemischen Erkrankungen wie Sklerodermie, progressiver muskularer Dystrophie oder Amyloidose oder als primare Storung auftreten. Eine Klassifikation der moglichen Entitaten ist in Tabelle 1 zusammengestellt. Dabei werden Storungen der glatten Muskulatur (Myopathie) von Storungen des Plexus myentericus abgegrenzt (Neuropathie).

Regulated secretory vesicles of neuroendocrine cells encompass two distinct types, i.e. hormone-storing large dense core vesicles (LDCV) and neuron-like small synaptic vesicles (SSVs). The membranes of the vesicles and the acceptor organelles contain proteins which are essential for targeted membrane fusion and protein transport (SNARE hypothesis). Membrane proteins of SSV analogues such as synaptophysin, synaptobrevin (v-SNARE) and synaptotagmin are key proteins of neurosecretion. The plasma membrane proteins syntaxin and SNAP25 (t-SNARE) are indispensible for this locking/fusion process. This study was done to identify the molecular components of LDCVs, SSV analogues and the SNARE-complex in neuroendocrine tumors. Immunohistochemical analysis using a panel of antibodies was done on file material from benign or low-grade malignant neuroendocrine tumors (n = 20) and high-grade malignant intermediate or small cell carcinomas (n = 27) of the gut, pancreas and lung. The statistical evaluation of our results indicate that the expression of all marker molecules of the regulated secretory pathway is significantly reduced in high-grade malignant carcinomas when compared to benign or low-grade malignant tumors. The reduction of the LDCV matrix protein chromogranin A and of the SSV membrane protein synaptobrevin is highly significant in high-grade malignant carcinomas, which may even loose these proteins. In contrast, the synthesis of synaptophysin and the t-SNARE-protein SNAP25 appears to be better maintained even in small cell carcinomas. We conclude that the immunohistochemical diagnosis of high-grade malignant neuroendocrine tumors should mainly be based on the identification of SSV- and SNARE-proteins, especially synaptophysin and SNAP25. These marker molecules of the regulated secretory pathway are valuable tools for the diagnosis and classification of neuroendocrine tumors and contribute to the understanding of cellular differentiation pathways.

To examine the prevalence of stool viruses and their role in the pathogenesis of diarrhea in HIV infection, we evaluated biopsies and repeated stool samples of 256 HIV-infected patients undergoing diagnostic endoscopy because of diarrhea (n = 136) or other symptoms (n = 120) for bacterial, protozoal, and viral enteropathogens. In 70% of the patients with diarrhea, at least one potential enteropathogen was detected. Stool virus was detected by electron microscopy in 17% (44 of 256), adenovirus in 6.6% (17 of 256), and coronavirus in 11.3% (29 of 256) of the patients. Adenovirus and coronavirus were detected more frequently in patients with diarrhea than in patients without diarrhea [adenovirus 10% (13 of 136) vs. 3.3% (4 of 120), p = 0.0129; coronavirus 15% (21 of 136) vs. 6.6% (8 of 120), p = 0.0142]. Sixty-one percent of patients harboring stool virus were coinfected by another enteropathogen. Pathogens other than stool virus were detected more frequently in patients harboring adenovirus (82%) than in patients without stool virus (48%, p0.025). Adenovirus and coronavirus are frequently detected in stools of HIV- infected patients and may contribute to diarrhea. Adenovirus infection may facilitate the occurrence of other intestinal pathogens. Due to frequent coinfections, detection of stool viruses reduces the rate of diarrhea of unknown origin only by approximately 5%.