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Biomedical subjects

P De Paoli

Publications and source records attributed to P De Paoli.

At least 19 recordsLinked to original sources
PubMed2005

Joint Nordic prospective study on human herpesvirus 8 and multiple myeloma risk.

An association between human herpesvirus 8 (HHV8) and multiple myeloma (MM) has been reported, though most studies have not confirmed such association. To follow-up on a previous prospective seroepidemiological study, where HHV8 tended to associate with MM risk, we linked five large serum banks in the Nordic countries with the Nordic cancer registries and 329 prospectively occurring cases of MM were identified, together with 1631 control subjects matched by age and gender. The HHV8 seroprevalences among cases and controls were similar (12 and 15%, respectively) and HHV8 seropositivity did not associate with the risk of MM, neither when considering positivity for lytic antibodies (relative risk (RR) = 0.8, 95% confidence interval (CI) = 0.5-1.1) nor for latent antibodies (RR = 0.6, 95% CI = 0.1-2.7). Similar risks were seen when analysis was restricted to case-control sets with at least 2 years lag before diagnosis (RR = 0.8, 95% CI = 0.5-1.2 and RR = 0.9, 95% CI = 0.1-4.2). In conclusion, the data indicate that HHV8 infection is not associated with MM.

Antibodies, Viral↗
PubMed2002

Laboratory diagnosis of human herpesvirus 8 infection in humans.

Human herpesvirus 8 (HHV-8) is causally associated with Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. Serological and molecular biology assays are used to investigate the biology of this virus in different populations and diseases. Serological assays are mainly used to study the prevalence of the viral infection and to predict the diagnosis of Kaposi's sarcoma and other HHV-8-associated cancers. The appearance of antibodies against lytic antigens precedes the appearance of antibodies against latent antigens, probably explaining the lower sensitivity of assays based on latent HHV-8 antigens. The lack of international reference serum panels is presently the major bottleneck for further progress in the field of HHV-8 serology. Molecular biological assays are an absolute requirement for both the diagnosis and the follow-up of HHV-8 infection. Qualitative methods have been particularly useful to elucidate the mode of transmission and the causal association between HHV-8 and HHV-8-associated diseases. Quantitative methods have become an essential tool to monitor the progression of the infection and the effects of antiviral therapies. This review analyzes the performance of the different serological and molecular biological assays available at present. The main conclusion is that more research is needed to define the most useful laboratory tests for the diagnosis of HHV-8 infection and to establish the clinical role of such tests.

Herpesviridae Infections↗
PubMed2001

Different rates of CD4+ and CD8+ T-cell proliferation in interleukin-2-treated human immunodeficiency virus-positive subjects.

BACKGROUND: Interleukin-2 (IL-2) has been used successfully to increase CD4 cell counts in patients who are human immunodeficiency virus (HIV) positive. The mechanisms involved in this phenomenon are unknown. We hypothesized that a differential proliferation rate of CD4+ compared with CD8+ lymphocytes could be related to the increase of CD4 counts and of CD4/CD8 ratios that occur in HIV+ patients during IL-2 treatment. METHODS: We enrolled in our study 14 HIV+ patients treated with IL-2 or with highly active antiretroviral therapy (HAART) during a 96-week observation period. Using flow cytometry, we measured longitudinally the expression of the Ki67 antigen in peripheral blood CD4+ and CD8+ lymphocyte subsets. RESULTS: Compared with HAART alone, IL-2 produced a rapid increase of Ki67+ proliferating CD4 cells and a concomitant increase of the CD4/CD8 ratios, whereas the corresponding CD8 proliferation increased slightly. On the contrary, HAART alone was effective in suppressing equally both CD4 and CD8 proliferation. CONCLUSIONS: Our results suggest a selective activity of IL-2 on CD4 T-cell proliferation; on the contrary, CD8-specific proliferation is affected minimally during treatment. This information may offer the potential to plan correctly immune activating regimens.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Lymphocyte subsets and viral load in patients with HIV-associated non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibody and chemotherapy.

The anti-CD20 monoclonal antibody Rituximab is a novel antitumor agent used in association with chemotherapy (CT) for the treatment of high-grade/intermediate non-Hodgkin's lymphomas (NHL) in HIV-negative populations. This therapeutic combination is currently also being explored in HIV-positive patients with NHL (HIV-NHL). The objective of our study was to determine CD4 and CD8T cell counts, HIV plasma viremia and proviral load in patients with CD20-positive HIV-NHL treated with Rituximab plus CT and highly active antiretroviral therapy (HAART). We studied eight patients with HIV-NHL treated by anti-CD20 and CT before, after three, and after six cycles of therapy; CD4, CD8 and CD19 lymphocyte subsets were measured by monoclonal antibodies and flow cytometry. HIV plasma viremia was determined by the b-DNA assay, and proviral load by a quantitative competitive PCR. CD4T cell counts remained stable after three cycles of therapy, while a significant reduction of this subset was present at the end of therapy. HIV plasma viremia was significantly reduced after the third cycle, but returned to pretreatment levels at the end of therapy; we also observed individual fluctuations of proviral load during therapy, this marker being increased in two out of three patients at the end of therapy. These observations suggest that Rituximab plus CT accelerated the rate of CD4 depletion and of HIV replication in the peripheral blood of HIV-NHL patients and that HAART may be able to delay these effects.

Adult↗
PubMed2001

Changes in thymic function in HIV-positive patients treated with highly active antiretroviral therapy and interleukin-2.

Despite its potent antiviral activity, highly active antiretroviral therapy (HAART) only exerts a marginal effect on CD4+ T-cell regeneration in HIV-infected subjects. Combination therapies aimed at boosting T-cell activity and maturation may provide an important contribution to the restoration of immune function. Here, we report the results obtained by a two-year follow-up of a cohort of HIV-infected patients treated with a combination of HAART and interleukin-2 (IL-2). In these patients, in addition to a series of quantitative virological and immunological parameters, we investigated T-cell regeneration by an immunophenotypic assay monitoring CD4+ naïve T cells, and by analysis of thymic function, through the quantification of the excision DNA products of T-cell receptor rearrangement (TRECs) in lymphocytes. Compared with HAART alone, we found that the IL-2 combination therapy was equally effective in reducing the levels of viremia and marginally more effective in decreasing proviral DNA load. Strikingly, the IL-2 combination produced a marked increase in the number of CD4+ T cells bearing a naïve phenotype (CD45RA+, CD62L+), which was apparent for over 96 weeks after therapy. To assess whether these cells were the product of improved T-cell generation, we exploited a competitive quantitative molecular assay to quantify TRECs in peripheral blood lymphocytes. Surprisingly, we found that the levels of these molecules were unchanged in these patients. These findings indicate that improved thymic function does not account for the early rise of CD4 naïve cells in HIV-positive patients treated with IL-2, and suggest that alternative mechanisms of T-cell maturation and differentiation are responsible for this event.

Adult↗
PubMed2001

Viral load of human herpesvirus 8 in peripheral blood of human immunodeficiency virus-infected patients with Kaposi's sarcoma.

Viral load is an important marker of activity of viral diseases for a number of viruses. We wished to evaluate whether the viral load of human herpesvirus 8 (HHV-8) in peripheral blood was a consistent feature of Kaposi's sarcoma (KS) patients and whether the viral load correlated with human immunodeficiency virus (HIV) RNA levels, CD4 counts, and/or the HHV-8 seroreactivity. Fifty-four consecutive plasma samples from 14 patients with KS were evaluated for HHV-8 viral load by quantitative real-time PCR. Samples were analyzed at the start of highly active antiretroviral therapy (HAART) and at different intervals during treatments. The median HHV-8 DNA load before HAART treatment was 8,998 (ranging from 170 to 40,100) copies/ml and 12,270 (ranging from 40 to 142,575) copies/ml during HAART. There were both increasing and decreasing trends. There was an association between HHV-8 DNA and HIV RNA viral loads (odds ratio [OR] = 5.40; 95% confidence interval [95% CI], 1.54 to 18.98) and between HHV-8 viral load and CD4 cell counts (OR = 7.24; 95% CI, 1.30 to 40.35). High HHV-8 viral load was also correlated with the titers of antibodies to the lytic HHV-8 antigen detected with immunofluorescence (P < 0.01), but not with antibodies to the latent HHV-8 antigen. In conclusion, we found that HHV-8 viremia in KS is associated with HIV viral load, CD4 cell counts, and lytic HHV-8 serological reactivity. HHV-8 viral load monitored by real time PCR might be useful for determination HHV-8 viral load during the follow-up of KS patients.

AIDS-Related Opportunistic Infections↗
PubMed2001

A multicenter study on central venous catheter-associated infections in Italy.

In a 1-year multicenter study the microbial colonization of 1154 central venous catheters (CVCs) was investigated. Catheters explanted either from immunocompromised or immunocompetent patients were collected and analyzed by five clinical microbiology laboratories located in Ancona, Aviano, Catania, Pavia and Rome, Italy. A further aim was to investigate, by scanning electron microscopy, the features of currently used catheters, both new and explanted from patients, analyzing their surface quality, the influence of the host protein biofilm on their microbial colonization, the modifications caused by their permanence in the body and the relationship between these factors and the occurrence of infections.

Anti-Bacterial Agents↗
PubMed2000

Seropositivity to human herpesvirus 8 in relation to sexual history and risk of sexually transmitted infections among women.

The mode of transmission of human herpesvirus 8 (HHV8) was investigated in two seroepidemiological studies of Swedish women who completed a questionnaire about sexual behavior. Seropositivity for HHV8 antibodies, measured using an indirect immunofluorescence assay, was linked to a high number (>10) of sexual partners (P < 0.004). It also correlated strongly with a history of other sexually transmitted diseases (STD; P < 0.0001), in particular with a history of Chlamydia trachomatis infection and condyloma acuminata. There was appreciable HHV8 seropositivity already among virginal or monogamous women (9%). In summary, HHV8 transmission to women in Sweden may occur nonsexually. When sexual transmission occurs, it appears to be associated with high risk-taking sexual behavior.

Adolescent↗
PubMed2000

Long-term treatment of spontaneously hypertensive rats with losartan and electrophysiological remodeling of cardiac myocytes.

OBJECTIVE: Cardiac hypertrophy due to pressure overload is associated with several cellular electrophysiological alterations such as prolongation of action potential duration (APD), decrease in transient outward current (Ito) and occurrence of the pacemaker current I(f). These alterations may play a role in sudden arrhythmic death, which is a major risk factor in myocardial hypertrophy and failure. Since angiotensin II is a key signal for myocyte hypertrophy, we tested if an 8-week treatment of old spontaneously hypertensive rats (SHR) with the antagonist of type-1 angiotensin II receptor (AT1), losartan (10 mg/kg/day), was able to influence the cellular electrophysiologic remodeling associated with cardiac hypertrophy. METHODS: Left ventricular myocytes were isolated from control (CTR) or losartan-treated (LOS) 18-month old SHR. Patch-clamped LVM were superfused with a normal Tyrode's solution (to measure action potential) or appropriately modified Tyrode's solution (to measure Ito and I(f)). RESULTS: Heart weight to body weight ratio (HW/BW) was significantly smaller in LOS (5.69 +/- 0.25 mg/g) than in CTR rats (6.67 +/- 0.37 mg/g; P < 0.05). Membrane capacitance, an index of cell size, was significantly reduced in LOS (342 +/- 12, n = 92) vs. CTR (422 +/- 14 pF, n = 96, P < 0.001). APD was significantly shorter in LOS than in CTR (at -60 mV: 197 +/- 23 vs. 277 +/- 19 ms, n = 28, P < 0.001); this effect was paralleled by a larger maximum Ito density in the LOS group (LOS: 15.1 +/- 1.4 pA/pF, CTR: 10.0 +/- 0.8 pA/pF) (n = 27, P < 0.02). I(f), elicited by hyperpolarizing steps (range: -60 to -130 mV), was consistently recorded in SHR cells; however, its maximal specific conductance was significantly lower in LOS than in CTR rats (28.6 +/- 3.6 vs. 54.2 +/- 8.0 pS/pF, n = 55, P < 0.001). Voltage of half-maximal activation (V1/2) of both Ito and I(f) was unchanged by the treatment. CONCLUSIONS: AT1 receptor blockade with losartan prevents the development of myocyte hypertrophy and associated electrophysiological alterations in old SHR.

Action Potentials↗
PubMed2000

Isolated cardiac cells for electropharmacological studies.

Single cardiac myocytes provide a model widely used to characterize the electrophysiological properties of drugs and to identify new therapeutic targets. This review focuses on isolation procedures to obtain single cardiac myocytes from several mammal species, including humans, and on patch-clamp technique as a useful method to investigate the molecular mechanism of druy actions.

Animals↗
PubMed2000

The effects of interleukin-2 therapy on the viral reservoir in HIV+ patients.

The initial idea that potent antiretroviral therapies could eradicate HIV infection within a few years of treatment has been recently challenged by the demonstration that the viral reservoir persists in the peripheral blood and in the lymphoid tissue. For this reason, an alternative approach based on the use of interleukin-2 has been developed. This cytokine, in fact, may be able to activate infected cells, promoting viral integration and replication, making HIV susceptible to antiretroviral treatments; this fact may ultimately contribute to the eradication of the virus itself. The measurement of the viral reservoir appears therefore essential to monitor the effects of combination therapies. We summarize here the technical approaches that have been used to quantitatively assess the HIV reservoir. We also show that the prolonged use of IL-2 in association with antiretroviral drugs promotes a reduction of the viral reservoir, but is unable to eradicate HIV, even after two years of therapy. The available in vitro and in vivo data do not exclude the fact that IL-2 may have a future in the treatment of HIV infection, though new therapeutic approaches using different strategies are required to clarify this issue.

Antiretroviral Therapy, Highly Active↗