[Intestinal tuberculosis: Easier overlooked than diagnosed]. / Darmtuberkulose: leichter zu übersehen als zu sichern.

Intestinal tuberculosis: Easier overlooked than diagnosed. The medical history of two Asian immigrants suffering from intestinal tuberculosis demonstrates the difficulties in finding the correct diagnosis. Intestinal tuberculosis resembles Crohn's disease with regard to clinical symptoms, macroscopic and microscopic intestinal findings. Sonographic, radiologic, endoscopic, and histological examinations facilitate distinguishing both entities. Diagnosis of intestinal tuberculosis is made by identification of the causative microorganism in tissue specimens. As this may be difficult and time-consuming, a therapeutic trial with anti-tuberculous agents may be warranted.

[Adult giant cell hepatitis with fatal outcome. Clinicopathologic case report and reflections on pathogenesis]. / Adulte Riesenzellhepatitis mit tödlichem Verlauf. Klinisch-pathologischer Fallbericht und Uberlegungen zur Pathogenese.

The occurrence of plasmodial giant cells in the liver is probably a morphological reaction pattern with the most diverse causes. In babies and infants, these changes occur in particular in neonatal hepatitis and intrahepatic and extrahepatic bile duct atresia. Viral infections and/or autoimmune reactions are discussed etiologically in giant cell hepatitis in adults (adult gaint cell hepatitis, AGCH), which is much rarer. In some of the cases, there were conspicuously high titers against paramyxoviruses. Giant cell hepatitis can occur in the course of HIV infection. These both indicate an infectious cause. However, the disease cannot be transmitted to chimpanzees. Apart from our case, only one further case is described in the literature in which a completed hepatitis A infection could be demonstrated serologically. In addition, the titer of antinuclear antibodies was raised in our patient. This autoimmune phenomenon is probably of crucial pathogenetic significance in our patient, especially since a hepatitis A infection on its own does not afford an adequate etiological explanation for the form of chronic and active hepatitis with consecutive cirrhotic transformation observed here.

Phase II clinical trial of combined natural interferon-beta plus recombinant interferon-gamma treatment of chronic hepatitis B.

BACKGROUND/AIMS: Alpha-interferon (IFN-alpha) is an effective treatment for chronic hepatitis B but only 25-40% of patients will profit from a long-term beneficial response to the currently recommended schedule of 3-6 MU given 3 times a week for 6 months. Clinical trials are therefore needed to investigate alternative modifications of interferon therapy, including combinations of different antivirals or immune modulators in order to improve the therapeutic approach to chronic hepatitis B infection. In a phase II trial we evaluated whether a combination of natural interferon-beta (nIFN-beta) with strong antiviral activity plus recombinant interferon-gamma (rIFN-gamma) with a predominantly immunomodulatory activity is able to increase the response rate compared to historical controls treated with IFN-alpha in a conventional regimen. METHODOLOGY: Forty patients with chronic hepatitis B were included in this trial of combined interferon therapy at a dosage of 6 MU nIFN-beta during week 1 followed by 3 MU for weeks 2-4 plus rIFN-gamma at a daily subcutaneous (s.c.) injection of 150 microg during the entire 4 weeks of the treatment period. Patients entered the trial on the basis of the following criteria: hepatitis B surface antigen (HBsAG), HBeAG and HBV-DNA positive for at least 6 months, HDV, EBV, CMV, anti-HIV negative, and chronic hepatitis proven on biopsy taken within 4 weeks of entry as well as 6 and/or 12 months after interferon therapy. The final diagnosis and classification of chronic hepatitis has been based on guidelines according to a revised classification of chronic hepatitis (Desmet 1994). The post-treatment follow-up was 12 months. RESULTS: The combined interferon therapy achieved complete responses with seroconversion from HBeAG to anti-HBe and a negative HBV-DNA (dot blot) test, as well as normalization of ALT activity in 15 patients, and partial response with negativation of HBV-DNA concomitant to a decrease in aminotransferase activity to near normal levels in 6 patients. Nineteen patients showed no response to viral markers but showed relief of clinical symptoms as well as pronounced decrease of serumtransaminase activity. Grading of liver biopsies demonstrated an improvement of histologic parameters after the interferon regimen in half of the evaluable patients (n=22). Histological response has been quantified by a reduction in the score of histological activity (HAI-index) from 12.6 before to 7.6 after interferon therapy, and in the inflammation and cellular degeneration score (ICD) from 9.9 to 5.2. Histological response, however, failed to show a consistent correlation with serologic response. This medium-dose combination of interferon-beta and interferon-gamma was tolerated very well by the patients, this good tolerability being explained by tachyphylaxis in response to daily interferon doses. No serious side effects or decompensation of liver function were observed during the 4-week period of therapy or the follow-up, despite the special clinical situation where 60% of the patients included in the study presented with histologically proven cirrhosis (35% of them with clinical manifestation of mildly decompensated cirrhosis). CONCLUSIONS: This short-term regimen of combined nIFN-beta + rIFN-gamma therapy in patients with chronic hepatitis B proved to be equieffective to long-term treatment with interferon-alpha and combines high clinical tolerability with good practicability, as it can be administered on an in-patient basis, ensuring close patient monitoring.

Expression of biglycan, decorin and proteoglycan-100/CSF-1 in normal and fibrotic human liver.

The immunohistochemical expression of the three small chondroitin/dermatan sulphate proteoglycans biglycan, decorin and proteoglycan-100 (PG-100), the proteoglycan form of colony-stimulating factor-1 (CSF-1), was studied in normal and fibrotic human liver. In normal liver tissue biglycan and decorin were clearly seen in the space of Disse, which was in contrast to a faint staining of PG-100. Biglycan and decorin were additionally detected around small bile ducts and in vessel walls. In patients with HBs-Ag positive, chronic active hepatitis decorin as well as biglycan showed strong immunoreactivity in fibrotic areas. In contrast to normal liver, PG-100 was visualized in bile duct epithelia. Therefore, PG-100 could serve as an immunohistochemical marker of the involvement of the bile duct system in chronic active hepatitis and progressive liver fibrosis.

Long-term experience in Wallstent therapy for malignant choledochal stenosis.

During a four-year period up to May 1993, 118 patients (mean age 69 years) with malignant bile duct stenoses were treated with a total of 127 selfexpanding 10-mm metal endoprostheses (Wallstent), most of them endoscopically (n = 102). Technical problems during and shortly after implantation occurred in five cases (4.2%), but could all be solved endoscopically. Serum bilirubin decreased from a mean of 8.0 mg/dl at presentation to a mean of 2.0 mg/dl after stenting. Nineteen patients died within the first three months (5% within the first 30 days); recurrent obstruction, as manifested by recurrent jaundice or cholangitis, or both, was encountered in 14%. Fifty-one patients who survived longer were followed up until death or for a minimum of 12 months (mean follow-up: 12 months). Stent patency rates in this group were 86% (six months), 72% (12 months) and 64% (18 months), survival for these time periods being 63%, 35% and 17%, respectively. No significant stent-related complications were noted; stent occlusion occurred in 12% of patients after a mean of 168 days, and was successfully managed endoscopically (thermal cleaning, implantation of further stents) in all cases. We conclude from our long-term follow-up data that patients surviving longer than three months are the ones most likely to benefit from Wallstent insertion for malignant jaundice.

Myofibroblast-like cells produce mRNA for type I and III procollagens in chronic active hepatitis.

In chronic active hepatitis the rate of collagen biosynthesis is largely determined by intracellular mRNA concentrations. To localize procollagen mRNA-producing cells, we investigated biopsy specimens from five patients with hepatitis B surface antigen-positive chronic active hepatitis and five patients without liver disease by in situ hybridization. We used type I and III procollagen cDNAs for transcription to (35S)-labeled probes. Parallel sections were stained with anti-actin monoclonal antibodies. Our results show that cells in which collagen synthesis is ostensibly enhanced can be localized by in situ hybridization of procollagen mRNAs. These cells were also anti-actin-positive in parallel sections and were localized in areas of inflammatory cell infiltration and necrosis. We conclude that myofibroblast-like cells may express procollagen mRNAs in chronic active hepatitis. Moreover, in situ hybridization may be a valuable diagnostic tool for providing additional morphologic information on the degree of fibrogenesis activity.

[Identification of procollagen mRNA in chronic active hepatitis B]. / Identifikation von Prokollagen-mRNAs bei chronisch aktiver Hepatitis B.

In situ hybridization is a tool for staining intracellular procollagen mRNAs with specific probes. Our study shows the amounts of procollagen mRNAs of types I and III to be increased in liver biopsies of five patients with chronic active hepatitis B as compared with five healthy controls. Parallel staining employing anti-smooth-muscle-actin antibodies was able to identify myofibroblast-like cells at the same localization where procollagen mRNAs were found. Consequently, these transformed Ito-cells might be the procollagen-producing cells.

[What is reliable in therapy of liver fibrosis?]. / Was ist gesichert in der Therapie der Leberfibrose?

Therapy of chronic active liver diseases associated with fibrotic transformation is usually restricted to unspecific antiinflammatory and immunosuppressive agents. However, recent advances in the biochemistry of collagen have allowed to define specific levels of collagen metabolism at which pharmacologic intervention can lead to reduced collagen deposition. The mode of action of some substances which interfere with collagen biosynthesis and degradation is described. However, the efficacy of these agents was tested in vitro exclusively or in animal experiments. Only few agents like colchicine were also studied in clinical trials. Reliable, safe, and specific antifibrotic agents for the clinical management of liver fibrosis do not exist up to now. Advances can be expected, however, from the development of novel inhibitors of prolyl-4-hydroxylase.

[Ultrasonic findings in aggressive abdominal fibromatosis]. / Sonographische Befunde bei aggressiver abdomineller Fibromatose.

A case of aggressive abdominal fibromatosis is reported. Ultrasonography revealed multiple inhomogenous, hypoechoic tumours within the mesenterium and the anterior abdominal wall. Some of these lesions had a hyperechogenic margin.

Evaluation of serum laminin P1, procollagen-III peptides, and N-acetyl-beta-glucosaminidase for monitoring the activity of liver fibrosis.

Chronic liver diseases are characterized by an increase in connective tissue components in liver tissue. The determination of Col 1-3 peptide of type III procollagen (P-III-P) in serum of patients seems to be a useful parameter of hepatic fibroplasia. Specific radioimmunoassays are available for Col 1-3 (P-III-P) and the Col 1 and Col 1-3 (P-III-P-Fab) peptides of type III procollagen and for laminin P1 fragment. These proteins and the activity of N-acetyl-beta-glucosaminidase (beta-NAG) were measured in 94 patients with chronic liver diseases, and in 74 healthy controls. In addition, direct immunofluorescence studies were done for laminin P1 in normal and fibrotic liver tissues. In normal human liver, laminin was found in the basement membrane of bile ducts and in blood vessel walls. In fibrotic liver tissue, laminin additionally occurred in periportal areas and in sinusoids co-distributed with other connective tissue components. In serum concentrations of P-III-P, P-III-P-Fab and laminin were higher in patients than in healthy subjects. Laminin concentration was increased in early stages of chronic liver disease, possibly as a marker of regeneration; the highest concentrations were in active cirrhosis and chronic active hepatitis. The determination of P-III-P and P-III-P-Fab provided information on synthesis and degradation of type III collagen: In inactive cirrhosis, Col 1 peptide was increased in relation to Col 1-3 peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of a sonographic secretin test in the diagnosis of pancreatic disease. Results of a prospective study.

In a prospective study the pancreatic duct diameter was measured sonographically before and after secretin stimulation in 20 healthy controls and 59 patients with upper abdominal pain, weight loss, and/or diarrhea. Whereas healthy controls and patients without pancreatic disease after secretin stimulation showed a distinct pancreatic duct dilatation of more than 90% of basal duct diameter, no distinct secretin-induced duct enlargement was observed in most patients with chronic pancreatitis. Patients with circumscript pancreatic duct stenosis even had a marked and longer-lasting duct dilatation after stimulation. In patients with anomalies of the pancreatic duct system, no uniform response was found after secretin injection. In this study the sonographic secretin test showed a sensitivity of 92% and a specificity of 95% for diagnosis of chronic pancreatitis. The results confirm that this diagnostic method can be recommended as a reliable screening test for pancreatic disease.

[Primary sonographic diagnosis of pancreatic duct calculi: the non-uniform aspect]. / Primär sonographische Diagnose von Pankreasgangkonkrementen: Uneinheitlicher Aspekt.

Four cases of sonographically visualised intraductal pancreatic calculi are reported. In three of these cases the calculi had been caused by chronic pancreatitis, and in one case by carcinoma of the head of the pancreas. The calculi did not present a uniform sonographic pattern, especially as regards echogenicity. A dorsal echo extinction was observed in three cases only. The non-uniform sonographic aspect of intraductal pancreatic calculi can probably be ascribed to differences in the lime content.

Sonographic imaging of the pancreatic duct. New diagnostic possibilities using secretin stimulation.

The pancreatic duct or at least parts of this structure can be demonstrated today by sonography in 75-85% of all persons examined. In 84 persons we have now measured the caliber of the sonographically visualized pancreatic duct in the region of the proximal body of the pancreas with special attention to dependence on age. The diameter of Wirsung's duct ranged from 1 to 3 mm (mean 1.9 mm) and increased significantly from the fifth decade of life onwards. After intravenous injection of the hormone secretin, healthy persons usually show a distinct duct enlargement, which also depends on age. Nine persons aged 19 through 35 (median 28) years showed a dilatation of the main pancreatic duct by about 110% following secretion injection. Nine further probands, 50-74 (median 58) years old, had a dilatation of about 70%. Eighteen patients with confirmed chronic pancreatitis and a pancreatic duct diameter not exceeding 4 mm generally showed no duct enlargement after secretin stimulation. We believe that periductal fibrosis, which is common in chronic pancreatitis, is the most important reason for these results. The use of the sonographic secretin test in the diagnosis of chronic pancreatitis should be considered.

Concentrations of 7S collagen and laminin P1 in sera of patients with diabetes mellitus.

Specific radioimmunoassays were used to quantify two basement membrane components, 7S collagen and laminin P1, in sera of 70 patients suffering from diabetes mellitus types I and II with and without clinical signs of chronic diabetic complications. Serum levels of both antigens were increased in diabetics compared to controls (p less than 0.001). Concentrations of 7S collagen were significantly different in diabetics with signs of microvascular damage compared to those without small vessel disease (p less than 0.05). The difference between laminin P1 concentrations in the two groups of diabetics was not significant (p less than 0.2). The augmented levels of circulating 7S collagen and laminin P1 may reflect alterations of basement membrane metabolism. Thus, the measurement of concentrations of these basement membrane components in serum may be a useful tool for monitoring the development of chronic diabetic complications.

Basement membrane components (7S collagen, laminin P1) are increased in sera of diabetics and activate platelets in vitro.

Serum concentrations of two basement membrane components (7S collagen and laminin P1) were detected by specific radioimmunoassays in 70 patients suffering from diabetes mellitus type I and II with and without clinical signs of microangiopathy. Serum levels of both antigens were increased compared to controls. 7S collagen concentrations were significantly different between the diabetics with signs of microvascular damage and those without small-vessel disease (p less than 0.05). Laminin P1 concentrations were also elevated, but the difference between the two groups of diabetics was not significant (p less than 0.2). Raised levels of circulating basement membrane proteins may indicate connective tissue activity and development of diabetic microangiopathy. In vitro 7S collagen is a moderate platelet activator inducing platelet spreading, aggregation, and malondialdehyde production. Laminin activates platelet spreading. As a part of the altered hemostatic system the activation of basement membrane components may contribute to the development of microvascular damage.