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Biomedical subjects

M Crovatto

Publications and source records attributed to M Crovatto.

At least 37 records · Page 2Linked to original sources

Interferon therapy in chronic hepatitis C virus: evidence of different outcome with respect to different viral strains.

The aim of the study was to assess the role of different viral strains of hepatitis C virus (HCV) in determining the outcome of the alpha-interferon (IFN) therapy. Fifty-seven patients (34 from Italy and 23 from Japan) with HCV-positive liver disease were enrolled in the study. The NS4 region of HCV was amplified in sera by "nested" polymerase chain reaction (PCR) using a primer pair synthesized according to the sequence of JK-1. The NS4 region was positive in 14 (41%) Italian and in 13 (56%) Japanese patients. In positive patients the sequence of the NS4 region was also obtained. Subsequently, HCV genotype was determined in all patients by PCR amplification of the core region. All patients received recombinant alpha 2a-interferon (IFN), 6 million units 3 times a week for 1 month followed by 3 million units 3 times a week for 5 months. The patients were followed for 1 year after the end of treatment. At the end of the follow-up, 17 (30%) had sustained normal levels of serum alanine aminotransferase (ALT). The outcome of treatment was not correlated with race, age, sex, histology, and pretreatment ALT level, but was significantly (P < 0.00001) associated with the presence of both the NS4-JK-1 region and HCV type II. Among the 27 NS4-positive patients, only 1 patient (3.7%) achieved a complete response, whereas the remaining 26 patients (95.3%) either were non-responders or relapsed after IFN was discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clinical and virological findings in mixed cryoglobulinaemia.

OBJECTIVES: As a close relationship has been established between mixed cryoglobulinaemia and hepatitis C virus (HCV) infection, the clinical, histological and virological findings of patients affected by mixed cryoglobulinaemia were determined. DESIGN: Hepatitis C virus infection was investigated by the presence of anti-HCV antibodies and PCR amplification of the 5' untranslated region (5' UTR), and the genotype of HCV was also determined according to Okamoto. A bone marrow biopsy was performed in all patients and liver and kidney biopsies when indicated. SUBJECTS: Eighty-two subjects affected by mixed cryoglobulinaemia were enrolled in this study. RESULTS: The prevalence of anti-HCV antibodies was high (83%); PCR amplification of the 5'UTR region was performed in 52 subjects and in 44 of them (85%) the results were positive. In the same subjects, the Core region amplification was positive in 46 cases (88%). A high prevalence of genotype II was found (54%). Chronic liver disease was present in 55 patients (67%). Bone marrow biopsies showed the presence of low-grade non-Hodgkin's lymphomas in 11 cases (13%). Membrano-proliferative glomerulonephritis was found in seven subjects (8%). CONCLUSIONS: Mixed cryoglobulinaemia is associated with HCV infection in the nearly all cases. Several HCV genotypes are involved in the pathogenesis of this disease. Mixed cryoglobulinaemia is associated with a high prevalence of chronic liver disease, low-grade non-Hodgkin's lymphomas and membrano-proliferative glomerulonephritis.

Aged↗

Low-grade malignant lymphoma, hepatitis C virus infection, and mixed cryoglobulinemia.

Because a close relationship has been established between mixed cryoglobulinemia and hepatitis C virus (HCV) infection, the clinical, histologic, and virologic findings of 31 patients affected by mixed cryoglobulinemia have been determined. HCV infection was investigated by the presence of anti-HCV antibodies and by polymerase chain reaction (PCR) amplification of the 5' untranslated region (5'UTR), and the genotype of HCV was also determined according to Okamoto et al (J Gen Virol 73:673, 1992). A bone marrow (BM) biopsy was performed in all patients, and liver and kidney biopsies were performed when indicated. The prevalence of anti-HCV antibodies was high (83.9%); polymerase chain reaction amplification of the 5' untranslated region was positive in 26 subjects (83.9%), and Core region amplification in 26 of 27 subjects (96.2%). A high prevalence of genotype II was found (76.6%). Chronic liver disease was present in 15 (48%) patients. BM biopsy specimens showed the presence of low-grade non-Hodgkin's lymphomas in 12 cases (38.7%), whereas, in 11 patients (35.5%), the BM infiltration was not monoclonal (reactive). Mixed cryoglobulinemia is closely associated with HCV infection. Apparently, only 1 patient was not infected by the virus. Several HCV genotypes are involved in the pathogenesis of mixed cryoglobulinemia. The disease is associated with a high prevalence of low-grade non-Hodgkin's lymphomas.

Aged↗

Different genotypes of hepatitis C virus are associated with different severity of chronic liver disease.

The presence of the "Japanese type" NS4 region was investigated in two series of patients (53 from Italy and 58 from Japan) with hepatitis C virus (HCV)-related chronic liver disease. The two populations were homogeneous as regard to age, male/female ratio, histological diagnosis, and serum aminotransferase activities. Genomic amplification was carried out by "nested" polymerase chain reaction (PCR) with a pair of primers synthesized according to the sequence of JK-1 isolated in Japan. The presence of viral replication was confirmed further by PCR amplification of the 5'NC region. The NS4 region of the Japanese strain was detected in 24 sera (45%) from Italy and in 44 (71%) from Japan. NS4-positive patients were significantly older and showed an ALT serum level significantly lower (P < 0.01) than NS4 negative cases in each group. Cirrhosis was significantly (P < 0.0007) more common in NS4-positive than in NS4-negative patients. The HCV genotype was subsequently obtained according to Okamoto. All the NS4-positive patients were infected by Type II, whereas in NS4-negative patients all four genotypes were present though Type II still constituted the majority. Cirrhosis was associated exclusively with Type II both in NS4-positive and -negative subjects. These data indicate that, although the positivity for NS4 "Japanese" region seems to be associated with a more aggressive liver disease, the most prevalent Type II predicts more specifically those who are likely to develop cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Infections in an Alpine environment: antibodies to hantaviruses, leptospira, rickettsiae, and Borrelia burgdorferi in defined Italian populations.

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.

Adult↗

Seroprevalence of antibodies to hantaviruses and leptospires in selected Italian population groups.

A study of hantaviral and leptospiral antibodies in selected population groups was performed. Among high risk subjects in the Rome area, Hantaan antibody was found in mammalogists (10%) and dialysis patients (6%), while none of the trappers, oarsmen, river policemen and firemen studied tested positive for antibodies to hantaviruses. In occupationally-exposed subjects (farmers, rangers, lumbermen, hunters) from rural and densely forested areas of northern Italian regions, the prevalence of Hantaan antibody ranged from 3.3% to 8.8%. In the positive cases the comparative antibody titration using different hantaviruses showed a predominance of Hantaan virus (titer 1:128) compared to Puumala virus (titer 1:32); no reactivity was observed with Seoul or Prospect Hill viruses. In Rome, leptospiral antibodies were found in trappers (21%) and oarsmen (5%) at a titer of 1:50 or more, with a predominance for the L. icterohaemorrhagiae serotype (85%). In the Alpine areas the leptospiral antibody prevalence was 12% and L. icterohaemorrhagiae and L. bratislava were the predominant serotypes. The presence of hantavirus infections, suspected after the first epidemiological survey conducted in central Italy, is now supported by the new data obtained in northern Italian regions. Furthermore, the recent observation of one case of Hemorrhagic Fever with Renal Syndrome (HFRS) in the Udine area, not far from the Yugoslavian border, strongly confirms the presence of one or more hantaviruses in Italy.

Adult↗

Phenotypic profile and functional characteristics of human gamma and delta T cells during acute toxoplasmosis.

Gamma and delta (gamma delta) T-cell receptor lymphocytes are increased during acute toxoplasmosis. These cells are BB3+ CD45RO+ CD8-. Purified gamma delta T cells failed to proliferate in response to Toxoplasma gondii antigen (stimulation index, 1.4 +/- 0.6) but were responsive to phytohemagglutinin stimulation (stimulation index, 20.8 +/- 1.9). Natural-killer-like cytotoxicity was strongly acquired only after in vitro culture of purified gamma delta T cells with recombinant interleukin 2 (40% +/- 7% specific lysis). Our data show that gamma delta T-cell receptor T cells with a peculiar phenotype are increased during human acute T. gondii infection.

Acute Disease↗

A subset of gamma delta lymphocytes is increased during HIV-1 infection.

The gamma delta T cell receptor (TcR) lymphocytes constitute 3-10% of human peripheral blood lymphocytes. Only a very small fraction of these cells is recognized by the delta TCS1 monoclonal antibody, directed against the V delta 1 chain of the receptor. We describe the immunological, virological and clinical data of a small group of seropositive subjects having high levels of gamma delta TcR T cells in the peripheral blood. Our flow cytometric studies show that most of these cells belong to the delta TCS1+ (V delta 1+), CD8 +/- (dim staining) subset. Patients with high gamma delta TcR T cell numbers were not characterized by the presence of an acute (IgM positive) or reactivated (as defined by high IgG titres against early antigen or IgA titres against viral capsidic antigen) Epstein-Barr virus infection. Cytomegalovirus infection was excluded by serological assays, and other herpes viral infections were not found after clinical examination. HIV p24 antigenaemia was present in two out of 11 subjects. AIDS patients had very high percentages of gamma delta TcR T cells. Altogether these data show that the selective expansion of delta TCS1+ cells in HIV1 seropositive subjects is not related to some exogenous antigen stimulation, but may be related to peculiar pathologic processes involving the immune system.

Antigens, Differentiation, T-Lymphocyte↗

Borreliosis risk after tick bite in north-eastern Italy.

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.

Adolescent↗

[Prevalence and determinants of HIV infection in 581 drug addicts in the Northeastern Italy, from 1984 to 1988].

Prevalence and determinants for human immunodeficiency (HIV) virus infection was assessed in 581 heterosexual intravenous drug users, recruited from public drug assistance centers in the northeast of Italy between 1984 and 1988. The overall seroprevalence rate for HIV antibody was 39% (95% confidence interval-CI-35-43%). HIV prevalence had risen from 32% in 1984-85 to 47% in 1986-88. Age was not associated with HIV infection risk, whereas gender was, women being at lower risk of infection than men (odds ratio-OR- = 0.7, 95% CI: 0,5-1.0). Seropositivity rates showed a strong east-west geographical gradient: intravenous drug users living in the western part of the study area had a nearly sevenfold higher risk of infection (95% CI = 4.4-13.9) than those living in the eastern part. Sharing of drug injection equipment was by far the most important risk factor. IVDUs who reported to always share injection equipment had a fourfold higher risk of HIV infection, as compared with those who never did (95% CI = 1.6-12.7). The duration of drug addiction (odds ratio = 2.6), the use of heroin in high-incidence cities (odds ratio = 2.3) and of cocaine in addition to heroin (odds ratio = 1.5) and the practice of prostitution (odds ratio = 2.3) were also important determinants of HIV infection. Over the study period, the odds ratios associated with area of residence decreased, whereas those associated with the use of heroin in high-incidence cities and with prostitution increased.

Adult↗

Risk factors for HIV infection in drug addicts from the northeast of Italy.

Prevalence and determinants of HIV infection were assessed in 313 parenteral drug addicts admitted to five Centers for Drug-Addict Assistance and two prisons located in the northeast of Italy (Friuli Venezia-Giulia), an area some distance from the major Italian cities first reached by the AIDS epidemic. The overall prevalence of HIV positivity was also rather high in this area, ie 30% with 24-36% confidence interval. The most important risk factors (besides syringe sharing applicable to all drug addicts), turned out to be of a geographical nature, ie living in Pordenone province (where a US military base is located) or coming from other endemic areas and having travelled long distances in the past three years. Prostitution also seemed to increase the risk of infection, but duration of drug addiction had little effect. In addition to persistent generalized lymphadenopathy (closely linked to HIV infection), reversal of helper:suppressor T-cell ratio was found in 67% of HIV positive individuals, but also in 31% of HIV negative ones. Clinical signs and symptoms strongly linked with HIV positivity were fatigue, weight loss, splenomegaly, fever and nocturnal sweats.

Adolescent↗

Immunologic abnormalities related to antigenaemia during HIV-1 infection.

The expression of phenotypic markers on T and B lymphocytes in long-term human immunodeficiency virus type 1 (HIV-1) seropositive, antigen negative patients, in seropositive, antigen positive individuals without AIDS and in seronegative intravenous drug abusers was examined by two colour flow cytometry. Seropositive, antigen positive patients showed decreased CD4+ lymphocyte numbers, causing lower CD4/CD8 ratios when compared to seropositive, antigen negative subjects. While CD4 CDw29+ (4B4) lymphocytes are selectively reduced in seropositive, antigen negative individuals, both CD4 CDw29+ and CD4 CD45R+ (2H4) lymphocytes are decreased when antigenaemia is present. An increased percentage of CD3 HLA DR+ activated T lymphocytes and of CD20+ (B1) Leu 8 negative activated B cells was seen in HIV-1 seropositive antigen positive patients. These results demonstrate that, in long-term seropositive individuals, antigenaemia is associated with peculiar phenotypic changes of lymphocyte subsets.

Acquired Immunodeficiency Syndrome↗

Selective depletion of the OKT 4+ 4B4+ subset in lymph nodes from HIV+ patients.

We have used 4B4 and 2H4 monoclonal antibodies in conjunction with OKT 4 to quantify T cell subsets in lymph node suspensions from human immunodeficiency virus (HIV) positive subjects with lymphadenopathy syndrome. The data indicate that the reduced OKT 4:OKT 8 ratio was due to a depletion of the OKT 4+ 4B4+ subset. In contrast, there were no differences compared to reactive controls, considering the OKT8+ subpopulation. These alterations may be related to the immunological deficiency associated with HIV infection.

Acquired Immunodeficiency Syndrome↗

Selective reduction of the OKT 4 positive 4B4 positive subset during HTLV III infection in humans.

Combinations of monoclonal antibodies defining the OKT 4 positive lymphocyte subset in the peripheral blood of intravenous drug abusers suggest that the 4B4 positive helper inducer population is greatly reduced in subjects infected with HTLV III. No differences were seen instead using different antibodies directed against various epitopes of the T4 molecule. These results suggest that the multiple marker assay could be very useful to define immunological status during HTLV III infection in humans.

Acquired Immunodeficiency Syndrome↗

HTLV-III infection among 315 intravenous drug abusers: seroepidemiological, clinical, and pathological findings.

Seroepidemiological, clinical, immunological, and pathological features were studied in 315 intravenous drug abusers (IVDA) seen in five centers for drug addicts' assistance in the Friuli Venezia-Giulia region of Italy, close to the borders of Austria and Yugoslavia. No case of AIDS has been observed. Sixty-five (21%) were affected by persistent generalized lymphadenopathy (PGL). HTLV-III seropositivity was noted in 86 (27%) of the overall 315 IVDA, in 50 (77%) of 65 patients with PGL, and in 1 (0.5%) of 205 blood donors tested as a control group. Patients with PGL had a significantly lower OKT4/OKT8 ratio than the rest of the IVDA population and controls. Systemic symptoms were present in 52% of the patients with PGL, the most frequent symptoms being fatigue and night sweats. In 20 patients with PGL, DR typing revealed a significant increase in DR-5 frequency and a significant decrease of DR-2 frequency. The predominant histological features in the lymph nodes taken from 25 patients consisted of an exuberant follicular hyperplasia, capillary vessel proliferation, and plasmacytosis. Nineteen (22%) females reporting occasional prostitution were compared to 10 non-IVDA female prostitutes and concomitantly evaluated. HTLV-III seropositivity was noted in 11 (58%) of 19 IVDA female prostitutes and in none of the 10 non-IVDA prostitutes. Thirty-five couples composed of both IVDA were compared to 24 couples composed of an IVDA and a non-IVDA. Among the 24 couples of whom one or both partners were seropositive, concordance in HTLV-III seropositivity was present in 5/11 (45%) couples composed of both IVDA, and in only 1/13 (8%) couples composed of an IVDA and a non-IVDA. This suggests that the sharing of contaminated needles, universally practiced by our IVDA population, plays a more important role in the transmission of HTLV-III than sexual contact.

AIDS-Related Complex↗