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Background/aim: A striking correlation between mixed cryoglobulinaemia and chronic hepatitis C virus infection has recently been described. Since membrano-proliferative glomerulonephritis is a rare complication of mixed cryoglobulinaemia, this study was undertaken to determine the prevalence of Hepatitis C virus infection in membrano-proliferative glomerulonephritis., Patients: Eighteen patients, selected among a group of 121 affected by mixed cryoglobulinaemia, with renal involvement were included in the present study. A group of 148 patients affected by renal disease of different aetiology and the general population (6,917 people) were used as control groups., Methods: The presence of anti-hepatitis C virus antibodies was determined by a commercial kit. The hepatitis C virus genotype was determined according to Okamoto. All patients underwent kidney and bone marrow biopsy, while the hepatic biopsy was performed in those showing signs of chronic liver disease., Results: In patients with renal involvement, the kidney biopsy showed the presence of membrano-proliferative glomerulonephritis Type I in all cases. Chronic liver disease was present in eleven patients (61%). All patients were positive for serum hepatitis C virus-RNA. Bone marrow biopsy was normal in five cases, while in the others paratrabecular foci of infiltration by small lymphocytes were present. In six of these, the massive bone marrow infiltration by lymphoplas-macytoid lymphocytes suggested the diagnosis of low grade non-Hodgkin's lymphoma. In the group of patients affected by other chronic renal disease, the prevalence of hepatitis C virus infection (3.1%) was not different from that of the general population (3.2%)., Conclusions: Hepatitis C virus seems to be the aetiologic agent of mixed cryoglobulinaemia and, consequently, of membrano-proliferative glomerulonephritis.

Background: In a previous paper, we reported on the short-term efficacy of alpha-interferon in the treatment of hepatitis C virus positive mixed cryoglobulinaemia., Aims: We investigated the long-term effects of therapy in a larger group of patients, and the viral and host factors able to influence the response to treatment., Methods: In 27 females and 15 males (mean age 54.8 +/- 9.1 years) affected by mixed cryoglobulinaemia, bone marrow biopsy and phenotyping of marrow cells were performed before treatment and at the end of follow-up. A liver biopsy was obtained from patients showing biochemical signs of chronic liver disease. The presence of hepatitis C virus was assessed by detection of serum anti-hepatitis C virus antibodies, and hepatitis C virus-RNA. The treatment schedule was 3 million units of recombinant interferon alpha-2b three times a week for one year. Follow-up lasted for 1 year after the end of treatment. The response was classified as follows: 1) Complete response: Disappearance of the cryocrit (or reduction of more than 50%) and of all clinical manifestations of the disease. 2) Partial response: Disappearance of all clinical signs of the disease, but reduction of cryocrit of less than 50%. 3) Minor response: Reduction of cryocrit of less than 20% associated with the disappearance of one or more (but not all) signs of vasculitis., Results: Anti-hepatitis C virus antibodies were present in 41 (95%) patients, and hepatitis C virus-RNA was detectable in all cases. Before therapy, marrow histology showed a massive monomorphous infiltration by plasmacytoid lymphocytes indicating the presence of low-grade non-Hodgkin lymphoma in 7 cases (16.6%). After therapy, 13 (31%) patients achieved a complete response, 23 patients (55%) a partial response, and 6 patients (14%) a minor response. Seven of the responders and all patients showing partial or minor responses relapsed a few months after withdrawal of therapy. At the end of the follow-up, only 6 patients had obtained complete remission. Bone marrow examination showed that B-lymphocytic monoclonal infiltrate had disappeared in 3 long-term responders. No difference was found between responders and non-responders/relapsers in terms of age, sex, duration of the disease, severity of symptoms, liver function tests, rheumatoid factor or complement levels, while the lack of response was associated with the presence of genotype 1b, liver cirrhosis, and high cryoglobulin level., Conclusions: Mixed cryoglobulinaemia is associated with a high prevalence of B-cell lymphomas. Alpha-Interferon is an effective agent for the treatment of this disease and seems able to determine regression of the lymphoproliferative disorder. The hepatitis C virus genotype and cryoglobulin level are the most important predictive factors of response to therapy.

Methods: Genomic and replicative forms of HCV-RNA in B lymphocytes were detected by RT-PCR, and HCV genotyping was performed using universal and type-specific primers for the core region. Immunoglobulin gene rearrangement was detected by RT-PCR., Results: The presence of genomic and replicative forms of HCV-RNA in the 5'NC region was investigated on total RNA extracted from subpopulations of PBMC. The frequency of HCV-RNA was higher in the B lymphocytes than in other PBMC. In two patients a larger sized band was present in the B lymphocytes and PMN; this band could represent either another form of HCV-RNA or a cross-reaction between cellular RNA and HCV primers. HCV-RNA detected using primers for the core region was negative in the patients examined. Immunoglobulin monoclonal gene rearrangement was present on the cDNA in all of the HCV and type II cryoglobulinemia positive samples except two; in contrast, it was absent in the HCV positive and cryoglobulinemia negative samples. The analysis of immunoglobulin monoclonal gene rearrangement on DNA showed the presence of new positive samples among the HCV positive, type II cryoglobulinemia negative patients, who had been negative when PCR was performed on cDNA. Denaturing sequencing gel showed clearer results than agarose gel., Conclusions: The early detection of immunoglobulin monoclonal gene rearrangement and expression is very important because it could provide evidence of the possible lymphoproliferative evolution of HCV infection. In addition, these investigations together with PCR product sequencing could show us the steps in the clonal selection of B lymphocytes towards malignant transformation, in which HCV plays a direct and/or indirect role.

Background: Since high CD23 expression and release have been reported in B-chronic lymphocytic leukemia (B-CLL), we investigated whether alpha-interferon or corticosteroids were able to modulate the expression and/or the release of this factor., Methods: CD23 expression was determined with FITC-labelled anti-CD23 monoclonal antibody, and sCD23 release with a sandwich enzyme immunoassay. Twenty-one patients affected by B-CLL (stage A or B) were studied before and after three different treatment regimens (alpha-interferon, corticosteroids, alpha-interferon+corticosteroids)., Results: CD23 was highly expressed in the B-cells of all patients, and expression was not modified by any of the therapies, sCD23 release from leukemic cells was significantly greater (p < 0.00001) in untreated subjects than controls, and in vitro treatment with phorbol myristate acetate (PMA) led to a 10-fold increase (p < 0.0001) in sCD23 secretion. On the contrary, PMA did not increase sCD23 release in normal B cells. Treatment with corticosteroids (either alone or associated with alpha-interferon) reduced sCD23 secretion from leukemic cells, whereas alpha-interferon alone was not able to modify sCD23 release., Conclusions: Our data support the hypothesis that CD23 plays a role in the maintenance and progression of B-CLL and that the pharmacological modulation of this receptor/lymphokine could be useful in the therapy of B-CLL.

From 1987 to 1991, a seroepidemiologic survey for antibodies to hantaviruses, leptospira, rickettsiae, and Borrelia was conducted in selected Italian population groups. In the mountainous areas of northeastern Italy, the prevalence of antibody to hantaviruses, as detected by indirect immunofluorescent antibody (IFA) assay, was 7.1%, 4.8%, 4.3%, and 4% in 265 forestry workers, 82 rangers, 395 farmers, and 75 hunters, respectively. Among 299 Alpine soldiers, the prevalence was lower (0.7%). Of those with Hantaan antibody, the reactivity pattern using Hantaan, Puumala, and Fojnica viruses suggested a prevalence of antibody to Hantaan virus, with titers reaching levels of 128. The presence of leptospiral antibodies (by microagglutination test), which included the prevalence of antibodies to Leptospira icterohaemorrhagiae, L. bratislava, and L. saxkoening serotypes, was observed in 10-12% of the farmers and forestry workers in these Alpine mountain regions. Only a few sporadic clinical cases of leptospirosis have been reported from these regions. Antibodies to Borrelia burgdorferi (by IFA) were observed in 19% of the rangers and forestry workers, with lower values in farmers (10%) and hunters (8%). These data suggest the presence of a large number of asymptomatic infections with B. burgdorferi and the leptospires in the densely wooded areas of the Alpine Italian regions. Furthermore, the recent identification of a case of Hantaan acute nephropathy in a man living in the mountainous northeastern area of Italy confirms the presence of hantavirus in the Italian Alpine zones, especially those near the Slovenian border.

Lyme Borreliosis is an infectious disease caused by the Borrelia burgdorferi spirochete transmitted to man by a tick bite. The aim of this study was to assess the predictive value of tick bites for the diagnosis of Borreliosis in a sample of 266 subjects residing in an endemic area of north-eastern Italy. In the serological diagnosis of Borreliosis, positive and negative predictive values of tick bites were found to be 24% and 88% respectively.

Prevalence and risk factors for human immunodeficiency (HIV) virus infection were assessed in 581 heterosexual intravenous drug users (IVDUs), recruited from eight public drug assistance centres in the northeast of Italy, an area at low risk for AIDS. The overall seroprevalence for HIV antibody was rather high, 39% (95% confidence interval (CI): 35-43%). HIV prevalence had risen from 32% in 1984-1985 to 52% in 1987-1988. Thirty-three per cent of female and 41% of male IVDUs had antibodies to HIV (p = 0.07). Seropositivity rates showed a strong east-west geographical gradient (from 16% to 60%, p = 0.005): IVDUs living in the western part of the study area had a nearly sevenfold higher risk of infection (odds ratio (OR) = 6.9, 95% CI: 4.4-13.9) than those living in the eastern part. Sharing of drug injection equipment (OR = 3.6), duration of drug addiction (OR = 2.6), use of heroin in high-incidence cities (OR = 2.3), use of cocaine in addition to heroin (OR = 1.5) and history of prostitution (OR = 2.3) increased the risk of acquiring HIV infection. Over the study period, the ORs associated with area of residence decreased, whereas those associated with the use of heroin in high-incidence cities and with prostitution increased.

This report describes two cases of peritoneal dialysis-related peritonitis caused by Fusarium species which have been incriminated in a variety of disease conditions. Treatment with 5-Fluorocytosine was unsuccessful, but removal of the catheter resulted in a rapid resolution of the infections.