Ragged-red fibres detected in paraffin sections by a monoclonal antibody to inner mitochondrial membrane.

An immunohistochemical method is reported using the M-II68 monoclonal antibody, which detects mitochondrial accumulations ("ragged-red fibres") in routinely processed (formalin-fixed, paraffin-embedded) muscle tissue. Ten cases with electron-microscopically and histochemically proven mitochondrial myopathy featured 4% to 24% ragged-red fibres. In a series of 50 muscle biopsies without mitochondrial myopathy, scattered ragged-red fibres (less than 0.1%) were present in a few normal and pathological muscles. The immunohistochemical method is specific for mitochondria, does not require frozen tissue and permits rapid examination of large areas.

Basement membrane proteins and type III procollagen in murine schistosomiasis.

The livers of female CBA mice were examined 9 to 10 weeks after subcutaneous infection with Schistosoma mansoni. Cryostat liver sections and isolated liver cells were examined by indirect immunofluorescence using specific antibodies against basement membrane proteins (laminin, fibronectin and type IV collagen and type III collagen precursor. Liver cells were isolated by collagenase digestion, purification on Percoll density gradients and centrifugal elutriation to yield enriched fractions of hepatocytes, endothelial and Kupffer cells (Fractions I, II, III respectively). Infected animals yielded more than three times the control number of non-parenchymal cells; electron microscopy revealed that the increase in Fraction II was due mainly to eosinophilic leucocytes and in Fraction III due to Kupffer cells and macrophages from the schistosomal granulomata. Studies of cryostat liver sections showed that the schistosomal granulomata contained dense deposits of type III collagen precursor and fibronectin in the distribution of the reticulin fibres but laminin and type IV collagen were conspicuous only in new vessels in the periphery of the granuloma. Isolated liver cells showed fibronectin on their surface. Immunofluorescence studies could not be performed on Kupffer and endothelial cell fractions because of marked non-specific fluorescence. These experiments indicate that centrifugal elutriation is a useful method for isolating the constituent cells of murine schistosomal granulomata.

Parameters predicting response to alpha-interferon treatment in chronic hepatitis C.

BACKGROUND/AIMS: Sustained response to alpha-interferon treatment for chronic hepatitis C is seen in only 25% of cases. Therefore, it is desirable to define pretreatment factors predicting responders. MATERIALS AND METHODS: Forty-nine patients with chronic hepatitis C were treated with a standard alpha-interferon regimen (3 x 3 MU s.c./week). Demographic, biochemical and immunological parameters, and HCV genotypes were obtained prior to initiation of treatment and evaluated for their value in predicting response to alpha-interferon therapy. RESULTS: Response, as defined by normalization of ALT, was 71% during interferon therapy and sustained response after discontinuation of interferon 24.5%. Patients infected with HCV-genotype 1b had significantly more often "community-acquired" disease. Their outcome was worse with a response rate of 44% during therapy and a sustained response of 12.5%, as compared to 87% and 27% respectively in patients infected with genotypes other than 1b. On multivariate analysis, absence of cirrhosis, HCV-genotype other than 1b, higher ALT levels and higher numbers of CD8 positive liver infiltrates were found to be predictors of response during alpha-interferon therapy. CONCLUSION: Response to alpha-interferon therapy seems to be influenced both by viral virulence factors and by the intensity of the host immune response to HCV.

Safety, tolerability and efficacy of peginterferon alpha-2a and ribavirin in chronic hepatitis C in clinical practice: The German Open Safety Trial.

The combination treatment of peginterferon alpha-2a (PEG-IFN alpha-2a; Pegasys) plus ribavirin (RBV) is recommended as a standard care for HCV infections. Side effects and aspects of efficacy and safety have to be balanced. This study evaluates clinical practice data on safety and efficacy of HCV treatment with PEG-IFN in combination with RBV over 24 and 48 weeks. This study was a phase III, multi-centre, open-label study with two treatment groups: PEG-IFN in combination with RBV for 24 or 48 weeks. The allocation to the treatment groups was at the discretion of the investigator; 309 patients entered active treatment: 90 patients received PEG-IFN plus RBV for 24 weeks and 219 patients PEG-IFN plus RBV for 48 weeks. A sustained virological response (SVR) was achieved in 48.9% of all patients. Genotype 1 patients with a 48-week combination treatment achieved an SVR of 39.9%. In the 48-week group a low baseline viral load was associated with a higher SVR rate (47.0% vs. 32.4%). For genotype 2 or 3 patients, the SVR was 67.9%. For these patients there was no relevant difference between patients with low and high viral loads; 97.7% of the patients experienced at least one adverse event. The incidence of serious adverse events was distinctly lower in the 24-week group (4.4% vs. 10.5%). This investigation confirms the well-known risk-benefit ratio found in controlled studies in a clinical practice setting. The safety profile is similar and shows the highest incidence of adverse events in the first 12 weeks of treatment.

[Pathogenesis and clinical aspects of primary liver cell carcinomas]. / Pathogenese und Klinik der primären Leberzellkarzinome.

The hepatocellular carcinoma is the most frequent primary liver cell carcinoma. On account of its geographical distribution with preferential occurrence in China, SE Asia and South Africa, exogenic causes are thought to be mainly responsible for its aetiopathogenesis. Besides mycotoxins, the hepatitis B virus infection (HBV) is particularly important. Integration of HBV-DNS into the hepatic cell DNS is considered to be an initiatory step in hepatocarcinogenesis. Clinically the tumour usually becomes manifest by upper abdominal complaints. Curative treatment can be promising only with very small tumours which can be detected most safely via ultrasound examination and alpha-1-fetoprotein determination.

[Methotrexate in the therapy of primary biliary cirrhosis]. / Methotrexat in der Therapie der primären biliären Zirrhose.

In a pilot study 5 females with primary biliary cirrhosis (PBC), histological stages I-III, were treated with methotrexate (7.5-15.0 mg by mouth weekly) for 15 months. Pruritus and fatigue decreased in 3 patients and cholestyramine could be reduced or discontinued. The concentration of alkaline phosphatase decreased significantly until the 6th month of treatment (P less than 0.002), but only after the methotrexate dosage had been increased to 15 mg weekly. However, the improvement in cholestasis parameters persisted until the end of the period of observation in only 3 patients in stages I and II. In only one case, initially in stage III with increased serum bilirubin concentration of 3.5 mg/dl, was there a change in the histological stage, to stage IV, after treatment. These preliminary results indicate that methotrexate can influence the symptoms and cholestasis enzymes in the early stages of PBC. Controlled studies should therefore only be conducted on anicteric patients in an early stage of the disease.

Antibodies to a trypsin sensitive pancreatic antigen in chronic inflammatory bowel disease: specific markers for a subgroup of patients with Crohn's disease.

The presence of antibodies against pancreatic juice (PAB) in patients with Crohn's disease has recently been reported. In our study sera from 273 patients with inflammatory bowel disease (222 with Crohn's disease, 51 with ulcerative colitis) have been examined for PAB and also for antibodies against gut tissues by means of indirect immunofluorescence. PAB were found in 68 of the 222 patients with Crohn's disease (31%), with titres ranging from 1/10 to 1/1280, and in only two patients with ulcerative colitis (4%), with titres of 1/20. None were found in 198 patients with various chronic inflammatory diseases and healthy control subjects. No differences were found between the PAB positive and negative patients when the following parameters were compared: disease activity (Crohn's disease activity index), involvement of bowel segments, incidence of extraintestinal disease, or treatment with anti-inflammatory drugs. Only seven of the patients with Crohn's disease had a history of pancreatic disease and of these, four had detectable pancreatic antibodies. Longitudinal observations of 40 patients with Crohn's disease showed a stable pattern for PAB, independent of disease activity and treatment. Partial characterisation of the PAB antigen, isolated from pancreatic juice, showed a trypsin sensitive macromolecular protein of more than 10(6) daltons not identical with a panel of defined exocrine pancreatic proteins. By contrast, antibodies against goblet cells (GAB) were found in 13 of 51 patients with ulcerative colitis (29%) and in none of the patients with Crohn's disease or control subjects. PAB were found as a highly specific serological marker for Crohn's disease and GAB for ulcerative colitis, but the relevance of PAB and GAB in the pathogenesis in Crohn's disease remains unclear.

[Lipoma of the small bowel]. / Dünndarmlipom - Seltene Ursache von Abdominalschmerzen und chronischen, blutigen Diarrhöen.

CLINICAL FEATURES: A 40-year-old female presented with chronic diarrhoea, intermittent abdominal pain, and melena. She reported of a 7 kg loss of weight within the preceding 6 weeks and showed signs of mild abdominal pain upon palpation of the right lower quadrant. Our clinical diagnosis was Crohn's disease or infectious gastro-enteritis as a CT scan showed thickening of the colonic wall in the right lower quadrant. However a previously performed ileocolonoscopy was normal. TECHNICAL EXAMINATIONS: Magnetic resonance imaging showed a thickened terminal ileum with extensive narrowing of the bowel lumen, in addition a polyp obstructing the lumen of the terminal ileum at 30 cm was detected during colonoscopy. THERAPY: The involved portion of ileum was resected. Intraoperatively an intussusception with the polyp forming the leading edge was found. Histological analysis led to the diagnosis "lipoma". Postoperatively the patient is now feeling well without any abdominal pain. CONCLUSION: Tumours of the small bowel are rare and are therefore often forgotten in the list of differential diagnoses of abdominal pain. If symptomatic, these tumours present mainly with uncharacteristic and unspecific signs, often leading to a delay in correct diagnosis as in the presented case. We therefore suggest that small bowel tumours should be considered at earlier stages in the differential diagnosis of unexplained abdominal pain in the middle-aged patient with signs of intestinal obstruction.

[Hepatitis-B-associated vasculitis. Clinical course with glucocorticoid and alpha-interferon therapy]. / Hepatitis-B-assoziierte Vaskulitis. Verlauf unter Therapie mit Glucocorticoiden und alpha-Interferon.

A 31-year-old women with chronic active hepatitis B (HBs antigen-positive, HBe antigen-negative) developed a painful petechia rash on both lower legs and the inner surface of the thighs. Histology of a skin biopsy revealed leucocytoclastic vasculitis. The affected skin areas contained HBs antigen and immunoglobulins. Immunosuppressive treatment with initially 60mg/d prednisolone improved the skin condition but activated the chronic hepatitis, GPT rising up to 240 U/l. The steroid treatment had to be discontinued. Subsequently the transaminases became normal but the vasculitis foci recurred. The patient was therefore given alpha-interferon, three times 5 mill. IU weekly subcutaneously for 6 months. The skin lesions disappeared and the circulating HBV-DNA decreased. But the HBs antigen could not be eliminated. It is to be noted that 12 months after the end of the alpha-interferon treatment the vasculitis has not recurred. - This case and published reports indicate that interferon treatment is effective against HBV-associated and immunoglobulin-complex mediated disease.

[Cryptococcal meningitis in AIDS: successful long-term prophylaxis with fluconazole]. / Kryptokokkenmeningitis bei AIDS: erfolgreiche Langzeitprophylaxe durch Fluconazol.

A 30-year-old, HIV-positive, man who had been repeatedly treated with amphotericin B for oral thrush, developed headaches, fever up to 38.5 degrees C, dizzy spells with falling tendency, as well as disorder of speech and word finding. Cerebrospinal fluid (CSF) contained 5700/3 cells, of which 90% were encapsulated yeast-fungus. Cryptococcal antigen titres were elevated both in serum (1:256) and CSF (1:1024), providing the diagnosis of cryptococcal meningitis. Intravenous treatment was started with amphotericin B, 0.3 mg/kg daily and flucytosine, 150 mg/kg daily. The clinical, microbiological and serological findings regressed after 4 weeks. After 8 weeks the creatinine concentration rose to 2.5 mg/dl. Because amphotericin B nephrotoxicity was suspected, further intravenous administration was stopped after a cumulative dosage of 2 g. He was placed on a prophylactic dosage of fluconazole, 100 mg by mouth twice daily. The cryptococcal antigen titre had fallen to normal within one year. The prophylactic regimen has been continued now for three years without recurrence or other fungal infection.

[Immunohistologic studies of differential HLA expression in patients with various intestinal diseases]. / Immunhistologische Untersuchungen zur differentiellen HLA-Expression bei Patienten mit verschiedenen Darmerkrankungen.

Histocompatibility antigens (HLA) play an important part in immunoregulation and in cell differentiation. This study analyses the expression of HLA class I and class II antigens (DR, DP, DQ) in intestinal biopsy specimen from patients with Crohn's disease, ulcerative colitis, GvHD, radiation colitis and intestinal adenomas using the indirect immunoperoxidase technique. 92 of 94 inflamed specimen from patients with inflammatory bowel disease showed a neoexpression of HLA II (DR greater than DP greater than DQ) on their epithelial cells. The intensity of HLA-DR neoexpression was significantly dependent on an endoscopic as well as a histological index of inflammation. All 75 non-inflamed specimen except 4 from patients with Crohn's disease did not show any evidence of HLA II display on the epithelium. 4 of 18 intestinal adenomas expressed HLA II on their epithelial cells without any correlation to the type of adenoma or the degree of cell dysplasia. Furthermore all specimen from a patient with intestinal GvHD showed an aberrant epithelial HLA II expression, but not that from radiation colitis. The expression of HLA class I antigens was similar in all biopsies studied. Our results suggest, that the epithelial neoexpression of HLA class II antigens may be an important event in the pathogenesis of various bowel diseases.

[Severe megaloblastic anaemia by triamterene in a patient with alcoholic liver cirrhosis (author's transl)]. / Schwere megaloblastäre Anämie durch Triamteren bei einem Patienten mit alkoholischer Leberzirrhose.

Mucosal ulceration and severe bone-marrow insufficiency with marked megaloblastic transformation occurred during treatment with triamterene in a patient with decompensated alcoholic liver cirrhosis and malnutrition. When the triamterene-containing preparation was stopped and folinic acid administered the haematological picture improved, but the patient died, with signs of hepatocellular insufficiency, of gastro-intestinal bleeding. The serum folic-acid level was markedly reduced due to the chronic malnutrition, while the vitamin B12 level was within normal limits. This observation indicates that when the pool of folic-acid coenzymes is reduced, triamterene can cause megaloblastic anaemia due to its folic-acid antagonism. Triamterene should, therefore, be given to patients with borderline folic-acid reservoirs, chronic alcoholism or during pregnancy, only under careful serial control of the blood picture.