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Biomedical subjects

L Sighinolfi

Publications and source records attributed to L Sighinolfi.

At least 19 recordsLinked to original sources

Benefits of a rapid HIV test for evaluation of the source patient after occupational exposure of healthcare workers.

Rapid human immunodeficiency virus (HIV) testing for the management of occupational exposure of healthcare workers significantly decreased the number of anti-retroviral post-exposure prophylaxis regimens started whilst awaiting HIV test results. The study confirmed an equivalent performance of the rapid test in comparison with HIV enzyme immunoassay, and suggests it is cost-effective. In addition, two other potential benefits emerged: reducing the number of source patients who remain untested and increasing the number of occupational exposures reported.

AIDS Serodiagnosis↗

Characterization of viro-immunological responses in a closely followed cohort of heavily pretreated patients: evidence from the GenPheRex Study.

OBJECTIVES: To assess prevalence and predictive factors of viro-immunological discordant trends in a cohort of heavily pretreated patients. METHODS: Factors associated with viro-immunological discordant trends either as categorical or continuous measures have been studied in 159 heavily pretreated HIV-positive patients from a multicentre prospective study of real- vs. virtual-phenotype. Univariate and multivariate logistic regressions were used to assess risk factors for categorical discordant responses, ceasing follow-up at week 32 since enough patients had been on the original drug combination for a sufficient amount of time to evaluate their immune response. Complementary linear regression analysis was performed over the entire 48 weeks' follow-up considering CD4 and plasma viral load (pVL) as continuous measures. RESULTS: Among 58 virological responder patients (> or =1 log10 HIV-1 RNA copies/mL decrease) and 101 virologically non-responders, immunological discordances (increase in CD4 count of< or > or =100 cells/microL) were observed in 58.6% and 38.6%, respectively. Baseline CD4 count was associated with discordant responses in both groups. Multivariable linear regression over the entire 48 weeks' follow-up demonstrated significant correlation between absolute decrease in pVL and increase in CD4 count (HR 28.06, 95%CI 35.32-20.79; P<0.001), also the use of protease inhibitors (PIs) in the salvage regimen (HR 36.57, 95%CI 15.45-57.68; P<0.001) and >8 months on treatment (HR 41.64, 95%CI 19.27-64.01; P<0.001) correlated with highly significant immune recovery. CONCLUSIONS: These data confirm that therapy, possibly including PIs, should be continued in heavily pretreated patients and that hard-to-reach pVL undetectability is not essential to obtain immunologic recovery; however, this is strongly increased by the degree of pVL reduction that should be achieved.

Anti-HIV Agents↗

Suicide probability and psychological morbidity secondary to HIV infection: a control study of HIV-seropositive, hepatitis C virus (HCV)-seropositive and HIV/HCV-seronegative injecting drug users.

BACKGROUND: Suicide ideation and psychological morbidity among HIV-positive patients has been the object of intense research. No study has investigated this area among injecting drug users (IDUs) infected with HIV and those infected with the hepatitis C virus (HCV), which has the same patterns of transmission of the HIV and may favour HIV replication and, possibly, HIV disease progression. METHODS: In order to examine the prevalence and characteristics of suicide ideation and psychological morbidity associated with HIV and HCV infection in IDUs, a sample of HIV+ (n=81), HIV-/HCV+ (n=62) and HIV-/HCV- (n=152) subjects completed the Suicide Probability Scale (SPS), The Brief Symptom Inventory (BSI) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: No difference was found between the groups as far as the mean scores on SPS and the risk of suicide (no-low risk category: 70.7% HIV+, 56.09% HCV+, 65.6% HIV-/HCV-). Estimated psychological morbidity (BSI) (26.9% HIV+, 27.1% HCV+, 25.4% of HIV-/HCV-) and BSI and HADS scores were comparable across the groups. CONCLUSIONS: Suicide ideation, psychological morbidity and anxiety and depression symptoms seemed not to be directly influenced by HIV-serostatus. Careful assessment of psychological symptoms and suicide ideas among IDUs, as a vulnerable segment of population at risk of HIV and HCV infections, needs to be routinely carried out in clinical settings.

Adolescent↗

Antiretroviral therapy in HIV-infected individuals in clinical practice: are the criteria for initiating and choosing the type of drug regimen based only on immunologic and virologic values?

OBJECTIVES: To determine factors associated with beginning antiretroviral therapy and with the number of drugs used. METHODS: Longitudinal study of 3169 HIV-infected individuals naïve from antiretroviral drugs at enrollment in 65 infectious disease clinics in Italy. Initiation of antiretroviral therapy and number of drugs used (i.e., < 3 vs. > or = 3 drugs) were the main outcome measures. Adjusted odds ratios were calculated by logistic models to establish cofactors of these two measures. RESULTS: From January 1997 to December 1998, 1288 (40.6%) individuals started therapy, 58.0% of whom were given a triple combination regimen. This regimen became more frequent over time. By multivariate analysis, high levels of HIV-RNA and low CD4 counts were the most important independent predictors of starting any type of therapy. A significant association was also found with HIV exposure category, reason for being antiretroviral-naïve, presence/absence of liver disease, presence/absence of a new AIDS-defining disease, and clinical centre. High levels of HIV-RNA and low CD4 counts were also the most important predictors of starting with > or = 3 drugs, compared to < 3 drugs, and men had an independent higher probability of starting with > or = 3 drugs, compared to women. The probability of starting with > or = 3 drugs significantly increased with calendar time. CONCLUSIONS: CD4 and HIV-RNA were the main cofactors of initiating both any type of therapy and therapy with > or = 3 drugs. The large variability among clinical centres suggests that clinicians are uncertain as to the exact timing of beginning therapy and the specific regimen, especially among women.

Adolescent↗

Illness behavior, emotional stress and psychosocial factors among asymptomatic HIV-infected patients.

BACKGROUND: Over the last years the way in which patients with chronic physical illness respond to their illness (illness behavior) has been explored by several studies. This study sought to examine characteristics of illness behavior and to investigate the association between illness behavior and psychosocial and clinical variables among asymptomatic HIV-infected subjects. METHODS: Seventy-three asymptomatic HIV+ outpatients completed self-report questionnaires to evaluate illness behavior (Illness Behavior Questionnaire), psychological stress symptoms (Brief Symptom Inventory), personality variables (External Locus of Control and Courtauld Emotional Control Scales) and social support (Social Provision Scale). RESULTS: Psychological morbidity ('caseness' = 34%) was associated with a pattern of illness behavior characterized by conviction of disease progression, irritability, dysphoria, psychological perception of illness and low denial. Individual capacity to express emotions, adequate levels of social support and low levels of depression, as well as clinical variables (high number of CD4+ cells, recent notification of HIV infection and nonintravenous drug use category) influenced a more adaptive illness behavior. Psychological stress and low CD4+ cell count were the main predictors of the affective dimension of illness behavior. CONCLUSIONS: Psychosocial variables resulted to influence the tendency to interpret illness in a nonadaptive way in asymptomatic HIV-infected subjects. Such variables merit to be routinely examined within the doctor-patient relationship in AIDS clinics.

Adaptation, Psychological↗

90K (Mac-2 BP) predicts CD4 decline in human immunodeficiency virus-infected patients with CD4 counts above 200 x 10(6) cells/L.

OBJECTIVE: To evaluate the ability of serum levels of 90K, previously reported as a progression marker of human immunodeficiency virus infection, to predict the future rate of CD4 lymphocyte decline. DESIGN: Retrospective analysis of data from outpatients enrolled in a multi-institutional study. PATIENTS: One hundred five human immunodeficiency virus-positive intravenous drug users who had at least six serial CD4 lymphocyte measurements and starting CD4 levels of 200 x 10(6) cells/L or higher. MAIN OUTCOME MEASURE: Rate of CD4 lymphocyte decline. RESULTS: During a median follow-up of 28 months (range, 20-36 months), the estimated loss of CD4 cells in the whole patient population was 3.4 x 106 cells/L per month (P = .0045). Subjects who were on zidovudine treatment at study entry showed an average loss of 3.8 x 10(6) cells/L per month, significantly higher than in untreated subjects (P = .02), but similar to the loss observed for those requiring initiation of treatment during the course of the study. At baseline, 56 subjects had 90K levels of 10 microg/mL or less, and 49 had more than 10 microg/mL. The rate of CD4 decline in the high-90K group was approximately 5 x 10(6) cells/L per month (P < .0015), whereas in the low-90K group it was not different from zero (P = ns). No difference emerged in the rate of CD4 decline when subjects were stratified according to baseline 90K levels and zidovudine treatment, beta2-microglobulin, or neopterin serum levels. CONCLUSION: 90K serum levels are predictive of CD4 decline.

Antigens, Neoplasm↗

Human herpesvirus 6 in human immunodeficiency virus-infected individuals: association with early histologic phases of lymphadenopathy syndrome but not with malignant lymphoproliferative disorders.

Preliminary evidence suggested that human herpesvirus-6 (HHV-6) may act as a cofactor in acquired immunodeficiency syndrome (AIDS) and may contribute to the pathogenesis of lymphoproliferative disorders occurring in individuals infected with the human immunodeficiency virus (HIV). To understand better the biological and clinical significance of HHV-6 infection in the context of HIV-related immunosuppression, the polymerase chain reaction was used to study the frequency and variant distribution of HHV-6 in peripheral blood mononucleated cells (PBMCs) from HIV-seropositive individuals, either asymptomatic or with lymphadenopathy syndrome (LAS) or with overt AIDS. Non-neoplastic and malignant lymphoproliferative disorders from both HIV-infected and HIV-seronegative patients were also investigated using the same series of samples for the presence of Epstein-Barr virus (EBV). When compared with healthy blood donors (12/42, 29%), HHV-6 prevalence in PBMCs showed a progressive decline in HIV-seropositive individuals with asymptomatic HIV infection (3/26, 11%) and in patients with LAS (1/13, 8%) and a significant reduction in patients with overt AIDS (1/20, 20%; P = 0.02). The decrease correlated with the number of CD4+ cells at the time of examination. In addition, HHV-6 DNA sequences were significantly more prevalent in LAS biopsies (13/20, 65%) than in HIV-unrelated reactive lymphadenopathies (2/10, 20%; P = 0.02) and the presence of HHV-6 sequences correlated closely with a histologic pattern of follicular hyperplasia (13/16, 81%; P = 0.003). Strikingly, HHV-6 prevalence decreased in PBMCs of LAS patients, suggesting that the likelihood of interactions between HHV-6 and HIV varies in different body districts. In particular, the demonstration that all HHV-6-carrying LAS samples were also positive for HIV infection suggests that LAS lymph nodes constitute one of the sites where biologically relevant interactions between the two viruses might occur. Also, the prevalence of EBV was higher in LAS (14/20, 70%) than in non-neoplastic lymph nodes from HIV-seronegative individuals (4/10, 40%), although the difference was not statistically significant. EBV was associated strongly with HIV-related malignant lymphoproliferative disorders, being detected in 100% of patients with Hodgkin's disease (HD) and 53% of B-cell non-Hodgkin's lymphomas (NHL). In contrast, the prevalence of HHV-6 DNA in HD and B-cell NHL arisen in HIV-infected patients (30% and 6% respectively) was remarkably lower and similar to that observed in lymphoproliferative disorders from HIV-seronegative patients. Finally, as observed in healthy individuals, HHV-6 variant B was more prevalent than variant A in benign and malignant lymphoproliferative disorders from bot HIV-infected and HIV-seronegative patients. These results suggest that the interactions between HHV-6 and HIV could be different in the various phases of HIV disease and in different districts; HHV-6 has probably no direct role in the pathogenesis of HIV-associated B-cell NHL and HD cases, and behave differently from EBV; and HIV-related immunosuppression does not alter the distribution of HHV-6 variants in these tissues, as observed in the case of EBV.

AIDS-Related Complex↗

The 90K tumor-associated antigen and clinical progression in human immunodeficiency virus infection.

We investigated the possibility that a secreted glycoprotein of approximately 90,000 daltons, termed 90K and identified as a member of the protein superfamily characterized by the scavenger receptor cysteine-rich (SRCR) domain, might have value as a predictor of progression to acquired immunodeficiency syndrome (AIDS) in subjects infected with the human immunodeficiency virus (HIV). Among 488 HIV-seropositive intravenous drug users with a median follow-up of 32.5 months, high levels of serum 90K at baseline proved to be a significant predictor of faster progression to AIDS, either as a continuous variable (log 90K; p < 0.0001) or as a dichotomous variable with an optimized cutoff point of 30 U/ml (p < 0.00001). Analysis of 90K in relation to known prognostic factors found an association with CD4 count, beta 2-microglobulin, and p24 antigen but none with neopterin. In multivariate analysis, the baseline 90K level was an independent predictor of AIDS. As compared with subjects with low levels of 90K, the relative risk of developing AIDS was 3.5 (95% CI 1.9-6.5) among those with high levels of 90K. The predictive value of 90K was maintained after stratification by baseline CD4 count: among subjects with > or = 500 x 10(6)/L CD4 cells, the proportion in whom AIDS developed was 10.5% for those with 90K levels < or = 30 U/ml as compared with 20% for those with 90K above the cutoff point (p = 0.006). Serum 90K is an independent predictor of the risk for progression to AIDS in HIV-infected subjects, including those whose CD4 counts have not fallen.

Acquired Immunodeficiency Syndrome↗

Human herpesviruses 6 and 7 in salivary glands and shedding in saliva of healthy and human immunodeficiency virus positive individuals.

The presence of human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) was investigated by the polymerase chain reaction in saliva specimens from healthy persons, donors affected by common cold or recurrent aphthous ulceration (RAU), and human immunodeficiency virus (HIV) positive patients, and in salivary gland biopsies. The sensitivity of the technique made it possible to detect as few as 5-10 target molecules in 15 microliters of saliva. HHV-6 was present in 63% of salivary gland biopsies and in 3% of salivas from healthy persons. No significant difference in the presence of HHV-6 was detected in specimens from donors with common cold, RAU, or HIV-infected patients. HHV-7 was present in 75% of salivary glands and in 55% of salivas from healthy persons. HHV-7 was detected with similar frequency in salivas from donors with common cold or RAU. Salivas from HIV-infected patients harbored HHV-7 with higher frequency (81%) and increased viral load. These results show that salivary glands are a site of persistent infection for both HHV-6 and HHV-7. However, the two viruses seem to differ in their biological properties: 1) HHV-6 is rarely present in saliva in detectable amounts, while HHV-7 is frequently detected; and 2) immunosuppression by acquired immunodeficiency syndrome (AIDS) increases the frequency of detection and the viral load of HHV-7, but does not have a significant effect on HHV-6 shedding in saliva.

Base Sequence↗

Reduced expression of macrophage-associated antigens on alveolar mononuclear phagocytes from acquired immunodeficiency syndrome.

In this study we evaluated the phenotype of alveolar mononuclear phagocytes recovered from the bronchoalveolar lavage fluid of 24 patients with human immunodeficiency virus infection (AIDS-related complex 8 patients. AIDS 16 patients) and 8 healthy individuals by using a panel of monoclonal antibodies known to react with tissue macrophages, in combination with a flow cytometer. The results showed that 90% of patients with AIDS present a marked reduction in the expression of several antigenic determinants (in decreasing order: CD68, CD36, CR1, CD11c, HLA-DR). The levels of antigen expression by flow cytometry seem to decline with disease progression, showing the most dramatic perturbations in patients with full-blown AIDS associated with pulmonary infections (especially Pneumocystis carinii pneumonia) and lower peripheral CD4 lymphocyte counts. In contrast, patients with AIDS-related complex or AIDS without histological or cultural evidence of pulmonary involvement showed, respectively, only minimal or medium antigenic decreases. However, only a minor proportion (16%, 20%, 20%, 25%, and 25% respectively) of human immunodeficiency virus infected patients (mostly with AIDS) had a significant reduction of the levels of CD4, CD14, CD45R, CD11b, and CD16 antigens in the alveolar macrophages. Since macrophages play a central role in the pathogenesis of AIDS, it may be postulated that the loss of various phenotypic markers on alveolar mononuclear phagocytes (some of them known for their important immunoregulatory actions) could have an important part in the pathogenesis of human immunodeficiency virus induced immunosuppression, and thereby condition the abnormal susceptibility to pulmonary diseases typical of human immunodeficiency virus-infected patients.

Acquired Immunodeficiency Syndrome↗

[Usefulness of microbial investigations in community-acquired pneumonia].

Community acquired pneumonia (CAP) is a common and well known disease, however there is no definite agreement on a common diagnostic-therapeutic strategy. To evaluate the usefulness of microbial investigations in the clinical practice we performed a prospective study on 93 consecutive patients with a diagnosis of CAP. Group I consisted of 46 patients that underwent a diagnostic protocol including sputum, blood cultures and detection of specific antibodies against M. pneumoniae, adenovirus, respiratory syncytial virus, and L. pneumophila. Group II consisted of 47 patients, in which only sputum samples were collected and cultured. No significant differences concerning the aetiologic diagnosis, the outcome and the length of hospitalization were observed in the two groups. The aetiological diagnosis was obtained in 17 patients (18.3%). As result of information obtained from microbiol tests, antibiotic therapy was changed only in 6 patients. Among the prognostic factors only a low albumin level was correlated with the length of hospitalization (p less than 0.01). From our data, the detection of microbial aetiology should not be routinely performed in patients with CAP, but should be reserved only to the severe forms.

Adult↗

Treatment of cerebral malaria by erythrocyte exchange.

A 33-years-old male presented with a severe malaria, caused by a chloroquine resistant strain of Plasmodium falciparum. The number of parasitized erythrocytes reached 20% and the patient had cerebral complication. During the second hospital day, an erythrocyte exchange was performed as an in addition to chemotherapy. The patient's clinical condition improved and the parasitemia disappeared. The erythrocyte exchange is recommended in severe malaria, when parasitemia greater than 10%, with or without cerebral, renal or blood coagulation complications.

Acute Disease↗