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Biomedical subjects

H Lobeck

Publications and source records attributed to H Lobeck.

At least 91 records · Page 5Linked to original sources

[Long-term follow-up of chronic hepatitis C after treatment with recombinant interferon alpha-2a].

As part of a multicenter randomized study 40 patients with chronic hepatitis C (HCV)-infection, 28 kryptogenic and 12 posttransfusional, were treated with recombinant interferon alfa (IFN alpha-2a) for 1 year in a dosage of 3 x 3 Mio. units per week versus dosis escalation after 8 and 16 weeks in serological non-responders. 36 of the 40 patients were followed over 3 years. The rate of patients with normalization of aminotransferases was 42% after two months of therapy, 28% at the end of treatment, 28% after 1 year and 23% after 3 years of follow-up. The polymerase chain reaction (PCR) for detection of HCV-RNA became negative after two months of treatment in 73%, at the end of therapy in 63%, after 1 year follow-up in 63% and after 3 years in 35%. All patients with persisting remission maintained HCV-RNA negative. Dosis escalation was realized in 8 patients without increase of responder rate. Antibodies against IFN alpha-2a developed in 4 (10%) patients without remarkable influence on the IFN-effect. Histological improvement at the end of treatment was observed in 61% including all patients with serological remission. The data support the prognostic relevance of the course of aminotransferases. If aminotransferases are not normalized during the first two months the treatment can be terminated. Persisting normalization of aminotransferases during 1 year after therapy and negative HCV-PCR result indicate maintaining remission.

Adult↗

Liver transplantation for PNH with Budd-Chiari syndrome. A case report.

A 54-year-old male patient with end-stage liver failure from Budd-Chiari syndrome due to paroxysmal nocturnal hemoglobinuria (PNH) underwent liver transplantation (OLT) in 1989. Retransplantation became necessary 1 year later when thrombotic occlusion of the portal vein and common hepatic artery led to graft loss after withdrawal of anticoagulation therapy because of several gastrointestinal bleeding episodes. The patient is now alive 3 years after the first OLT. To the best of our knowledge and according to the literature, this is, to date, the longest that any PNH patient has survived after liver transplantation. Although the course of this patient was complicated in a way similar to that reported for other cases in the literature, patients with PNH should not, in principle, be excluded from liver transplantation. Lifelong anticoagulation with coumarin and the use of steroids together with cyclosporin reduce the risk of recurrent thrombosis and PNH crises.

Budd-Chiari Syndrome↗

[Esthesioneuroblastoma: diagnostic conformation by immunohistology and electron microscopy].

The aesthesioneuroblastoma (olfactory neuroma) is a rare neuroepithelial tumour of the nasal cavity, the clinical symptoms of which become manifest very late in most patients. In general, with the light microscope used routinely (fixation of the specimens with formaldehyde, staining with haematoxylin-eosine) a malignant round cell neoplasia can be recognised without further differentiation. To ensure the diagnosis of an aesthesioneuroblastoma, immunohistological techniques (vimentin, S-100 protein, neurofilaments, neuron-specific enolase) are undoubtedly necessary. In some cases of unclear findings the electron microscope might be used to prove an aesthesioneuroblastoma. The immunohistological and electron microscopic features of aesthesioneuroblastoma are demonstrated and problems of histological differential diagnosis are discussed.

Adult↗

[Primary sclerosing cholangitis (PSC)--humoral immune phenomena, pathogenetic aspects and therapeutic possibilities].

There are about 80% antibodies in PSC against cytoplasmatic antigens of neutrophilic granulocytes of the perinuclear type (pANCA), inconstantly there are antinuclear antibodies (ANA) too, but no antimitochondrial antibodies. The frequent association of PSC with colitis ulcerosa suggests an enterobacterial aetiopathogenesis. PSC sera show clear bands at 60-90 kD and at about 10 kD in the immunoblot with enterobacterial proteins as antigens. Antibodies against enterobacterial lipopolysaccharides and lipid A are to be found in patients with PSC corresponding to the normal collective. After long-term immunization with enterobacterial antigens PSC-like changes with circulating ANA can be induced in mice and rabbits. PSC, comparable to primary biliary cirrhosis, also reacts to treatment with ursodesoxycholic acid but it scarcely reacts to immunosuppressive therapy. At the final stage of the disease liver transplantation is indicated. In our clinic up to now 16 patients with PSC have undergone a transplantation with a one-year-survival rate of 88%. Confirmed re-manifestations of PSC in the transplant have not been diagnosed up to now.

Animals↗

Multiple drug resistance gene expression in human renal cell cancer is associated with the histologic subtype.

Overexpression of p170 glycoprotein, the product of the multiple drug resistance (mdr) gene, has been associated with resistance to various cytotoxic drugs used in the treatment of human neoplasms. Normal renal epithelial cells express p170 as a function of their secretory capacity. Because renal cell carcinomas (RCC) respond poorly to chemotherapeutic regimens, p170 expression was studied in primary RCC. Such expression was measured in 40 human RCC and normal kidney tissues using immunohistochemical staining with the monoclonal antibody C-219. Staining intensities of the whole tumor and of different areas of the cryostat sections were transformed into digital numbers using an algorithm designed for this purpose. In most tumors, an inhomogeneous staining pattern and a correlation between grade of differentiation and C-219 immunoreactivity was observed. A comparison of the tumors according to their histopathologic subtypes showed clear differences. The means (range) of the staining intensities of the different types of RCC: clear cell carcinoma Grade 1 (n = 3), 2.0 (2.0 to 2.0); clear cell carcinoma Grade 2 (n = 19), 0.8 (0.0 to 2.9); clear cell carcinoma Grade 3 (n = 5), 0.1 (0.0 to 0.2); tubular carcinoma (n = 4), 2.0 (2.0 to 3.0); anaplastic carcinoma (n = 8), 0.05 (0.0 to 0.2); oncocytoma (n = 1), 0.0 (0.0 to 0.0); and normal kidney (n = 40), 0.5 (0.0 to 2.0). The differences between anaplastic, clear cell, and tubular carcinoma were significant (P less than 0.001 by Kruskal-Wallis test). In addition, the difference between the three subgroups of clear cell carcinoma was significant (P less than 0.01). It was concluded that the histopathologic subtypes of RCC correlate with the degree of mdr gene expression, as determined by staining with the C-219 monoclonal antibody.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Hepatitis C virus reinfection in allografts after orthotopic liver transplantation.

From September 1988 to May 1991, 160 orthotopic liver transplantations were performed in our hospital. Twenty-four patients had end-stage cirrhosis caused by chronic non-A, non-B hepatitis. Antibodies against hepatitis C virus were documented before and after orthotopic liver transplantation in 13 patients. Studies using the polymerase chain reaction demonstrated hepatitis C virus RNA in the serum and liver tissue of 17 patients (10 of whom tested positive for hepatitis C virus antibodies) before orthotopic liver transplantation. Tissue samples taken from liver grafts during the operation were hepatitis C virus RNA negative in every case. Ten of these 17 patients had positive hepatitis C virus RNA findings in serum and liver biopsy specimens within the first month after surgery. One patient died of Mucor sepsis 2 mo after orthotopic liver transplantation. Another patient died of multi-organ failure 3 mo after a retransplantation. Two patients underwent retransplantation for graft rejection at 2 and 3 mo, respectively. One year after orthotopic liver transplantation, hepatitis C virus RNA was demonstrated in allograft biopsy specimens in 13 of 15 patients. Two patients remained hepatitis C virus RNA negative in repeated biopsies up to 12 mo. Mild portal and lobular hepatitis developed within 6 months of orthotopic liver transplantation in four patients and within 1 yr in five additional patients. The data suggest that persistent hepatitis C virus reinfects the allograft in most cases, but the risk of acute organ damage caused by hepatitis C virus reinfection is low.

Adult↗

Mutations in the ras protooncogenes are rare events in renal cell cancer.

Mutations in codon 12, 13 or 61 of one of the three ras genes, Ha-ras, Ki-ras, and N-ras, convert these genes into active oncogenes. To determine the role mutated ras genes play in the carcinogenesis of renal cell carcinoma, we analysed tumour DNA and unaffected renal tissue derived from 55 patients. The polymerase chain reaction technique was used to amplify DNA fragments containing Ki-, Ha-, and N-ras codons 12, 13, and 61. The amplified fragments were then probed on slot-blots with labeled mutation-specific oligomers. A single Ki-ras mutation (codon 12, gly- greater than val) was detected in a patient with a pT2N2M1 tumour. We concluded that ras oncogene mutations do not play an important role in the initiation of renal cell carcinoma.

Adult↗

Distribution of cytokeratins in oral cytological smears of HIV-infected patients.

Cytological smears (CS), taken from the lateral border of the tongue of HIV-seropositive patients (HIV+) (n = 34) and of seronegative controls (HIV-) (n = 16), were examined by means of immunocytochemistry (APAAP) for the distribution patterns of different cytokeratins and MHC class II antigens. Compared with HIV- patients in CS of HIV-infected patients cornification associated cytokeratins 10/11 were increased, while the number of keratinocytes positive for cytokeratins 13/16 was comparable in both groups. Expression of simple epithelial cytokeratins 19, rarely observed in CS of HIV- patients, was a frequent findings in CS of HIV+ patients. Keratinocytes positive for MHC class II antigens were observed in CS of 12/34 HIV+, while all control CS were negative. In the group of HIV+ patients no correlation was found between the clinical presence of HL and the expression of cytokeratins or class II antigens. The altered distribution of cytokeratins may reflect local responses to proliferative stimuli or local inflammation due to the presence of microbial antigens or may occur as a general unspecific reaction in the setting of systemic viral infection. This non-invasive technique seems to be a valuable tool to determine the proliferation rate of oral epithelial cells.

Adult↗

Follow-up of recurrent hepatitis B and delta infection in liver allograft recipients after treatment with recombinant interferon-alpha.

Reinfection of the graft with hepatitis B virus (HBV) and hepatitis delta virus (HDV) is a potential complication in patients undergoing orthotopic liver transplantation (OLT). Therefore, we added recombinant interferon-alpha (rIFNa) to the standard immunosuppressive regimen in 11 patients who received transplants following liver failure attributed to cirrhosis B (n = 10, with HDV co-infection in four cases) or fulminant hepatitis B (n = 1). Patients were treated with rIFNa for periods ranging from 2 to 3 months between the first and the 13th month after OLT. All patients received immunosuppressive treatment with low-dose corticosteroids, azathioprine and cyclosporine. Anti-HBs hyperimmune globulin was also administered. None of the patients showed evidence of severe allograft rejection. Seven patients suffered HBV reinfection of the graft with histological signs of acute hepatitis in five cases and transition to chronic hepatitis in one patient. Treatment with rIFNa did not prevent or reduce HBV replication. Reinfection of the graft with HDV was demonstrated by PCR in four patients co-infected with HDV. During treatment with rIFNa liver biopsy specimens from three reinfected patients were transiently negative for HDV antigen but not for HDV RNA, and the sera from two patients were transiently negative for HDV RNA. The data indicate that rIFNa can reduce HDV replication in reinfected liver allografts.

Adrenal Cortex Hormones↗

Detection of light chain restriction in chronic B-lymphoid leukaemia and B-non-Hodgkin's lymphoma.

The determination of immunoglobulin light chain restriction using monoclonal and polyclonal antibodies is a rapid method for the detection of a neoplastic B-cell-population. Cytocentrifuge preparates of mononuclear blood cells from 42 patients with chronic B-lymphoid leukaemia and of lymph node aspirates from 24 patients with B-non-Hodgkin's lymphoma were examined using the alkaline phosphatase-antialkaline phosphatase (APAAP) method. Monoclonal antibodies from different commercial sources and rabbit polyclonal antibodies were used in this study. Staining with polyclonal antibodies demonstrated light chain restriction in 65 cases. The leukaemic cells of a patient with hairy cell leukaemia did not express light chain immunoglobulins. Monoclonal antibodies from two manufacturers demonstrated monotypic staining for light chains in all cases with light chain immunoglobulins. Monoclonal antibodies from four manufactures failed to show monotypic light chains in 5, 21, 25 and 28 of the 65 cases. All investigated antibodies detected a similar percentage of light chain-positive lymphocytes in 10 healthy persons. We conclude that not all investigated monoclonal antibodies are suitable for detection of light chain restriction in B-non-Hodgkin's lymphomas and chronic B-lymphoid leukaemias. However, using selected monoclonal antibodies or rabbit polyclonal antibodies the APAAP method is very sensitive for detection of light chain restriction in these disorders.

Antibodies↗

Disseminated cytomegalovirus infection of the female genital tract.

A woman with severe immunosuppression provoked by the acquired immunodeficiency syndrome developed a disseminated cytomegalovirus infection of the genital tract. Using in situ hybridization and the APAAP technique, cytomegalovirus was detected in epithelial and endothelial cells as well as in macrophages in the vulva, the vagina and the cervix uteri.

Acquired Immunodeficiency Syndrome↗

Keratins as molecular markers of epithelial differentiation: differential expression in crypt epithelium of human palatine tonsils.

The expression of keratins in the stratified squamous nonkeratinizing epithelium lining the surface and the crypts of human palatine tonsils was analyzed by high-resolution gel electrophoresis, immunoblotting, and immunohistochemical techniques. In contrast to the superficial epithelium, which showed a fairly constant keratin composition consisting of the neutral-to-basic keratins K4, K5, K6, and K8 and the acidic keratins K13, K14, K16, and K19, the keratin profiles of tonsillar crypt epithelial cells were found to be more variable, particularly with respect to the expression levels of K4 and K13. These were identical to those of surface epithelium, reduced, or abolished. Since K4 and K13 characterize the mature stage of differentiation in squamous nonkeratinizing epithelia, their decrease is indicative of an incomplete epithelial differentiation. Immunohistochemical analyses confirmed this hypothesis and allowed us, furthermore, to correlate the expression of K13 with the morphologic alterations of tonsillar crypt epithelium in the course of reticulation.

Adolescent↗

Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non-B and frequency of circulating antibodies to hepatitis C virus (HCV).

The natural course of chronic hepatitis non-A, non-B (HNANB) was documented for 3-20 yr (mean 8 yr) in 86 patients, who attended our special ambulance between 1981 and 1988. Sixty five of the 86 patients (75%) were positive for circulating antibodies against hepatitis C virus (HCV) (anti-HCV). Twenty four patients had chronic posttransfusion (PT)-HNANB (18 anti-HCV-positive; 75%), and 62 patients had sporadic (S)-HNANB (47 anti-HCV-positive; 75%). Twenty nine per cent of patients with chronic PT-HNANB had sustained normalization of aminotransferases after a period up to 5 yr, 55% demonstrated chronic persistent hepatitis (CPH) and 16% progressed to chronic active hepatitis (CAH) with transition to cirrhosis. In the group with chronic S-HNANB, 2% of patients showed remission, 43% had stable CPH and 55% progressed to CAH or cirrhosis. However, development of cirrhotic complications required many years. Transition from CAH to CPH or remission was not observed. The results indicate that 75% of both patients groups with chronic PT- and S-HNANB are infected with the same agent, of which antibodies are detected by the new anti-HCV assay. There was no statistical association between the severity of the disease and the presence of anti-HCV. The different proportions of progressive courses in chronic PT- and S-HNANB might be explained by the patient recruitment.

Blood Transfusion↗

Immunocytochemical analysis of lymph node aspirates in patients with human immunodeficiency virus infection.

Thirty four patients positive for human immunodeficiency virus (HIV) who had lymphadenopathy were investigated using fine needle aspiration. Cytological analysis included immunocytochemical investigation with the alkaline phosphatase-antialkaline phosphatase (APAAP) method. All patients had confirmation of cytological diagnosis by lymph node biopsy. Fifteen aspirates with follicular hyperplasia were evaluated. Eleven patients showed B cell predominance. The B cell population did not show light chain restriction. Ten patients with B cell non-Hodgkin's lymphoma (five with Burkitt's lymphoma and five with B cell immunoblastic lymphoma) were investigated. Nine out of 10 cases were monoclonal with respect to their light chain determinants; only one case with Burkitt's lymphoma with partial lymph node metastasis did not show light chain restriction. The cytological diagnosis included two mycobacterial infections and four cystic lesions. Histological investigation was necessary to diagnose the extent of lymph node disease caused by Kaposi's sarcoma. These findings indicate that the immunocytological investigation of lymph node aspirates is useful for evaluating lymphadenopathy in HIV positive patients.

AIDS-Related Complex↗

[Long-term treatment of cryptogenic hepatitis C using recombinant interferon alpha].

In a pilot study 15 patients with cryptogenic chronic hepatitis non-A, non-B received human recombinant interferon alpha (rIFNa) at a dosage of 5 million units 3 times per week for periods of up to 4 months, followed by an additional 4-month course of treatment with 2 million units 3 times per week after an observed reduction in serum aminotransferase levels. Ten of the 15 patients demonstrated antibodies to hepatitis C virus (HCV). Pretreatment histological examinations revealed evidence of chronic aggressive hepatitis in 12 patients, 4 with signs of cirrhosis, and chronic persistent hepatitis (CPH) in the remaining 3 cases. Normalization of serum aminotransferase levels was documented in 9 patients (7 anti-HCV-positive), and a significant reduction occurred in 2 additional anti-HCV-positive cases. Follow-up biopsy at 8 months in 7 of the 11 responders documented improved histological findings in every case. Five patients with CAH in the initial study had discrete residual portal inflammation or mesenchymal reaction in the second histological examination. Clinical follow-up is currently at 12 month, and 3 anti-HCV-positive responders have normal aminotransferase levels. The data show that a subset of patients with chronic hepatitis C will demonstrate remission of disease after an 8-month course of treatment with rIFNa.

Adult↗