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Biomedical subjects

L Ortona

Publications and source records attributed to L Ortona.

At least 55 records · Page 3Linked to original sources
PubMed1997

Diagnosis of AIDS-related focal brain lesions: a decision-making analysis based on clinical and neuroradiologic characteristics combined with polymerase chain reaction assays in CSF.

OBJECTIVE: To identify disease patterns in AIDS-related focal brain lesions (FBL) and to design a decision-making strategy for differential diagnosis. DESIGN: Prospective study. Probabilities of CNS disorders were calculated using Bayes' theorem according to clinical variables (mass effect at CT or MRI, Toxoplasma serology, anti-Toxoplasma prophylaxis) and to the results of polymerase chain reaction (PCR) assays. PATIENTS: 136 consecutive HIV-infected patients with a definitive diagnosis of FBL-causing disorder observed from 1991 to 1995 in a single clinical setting. INTERVENTIONS: Patients underwent empiric anti-Toxoplasma therapy. After 3 weeks, patients with progressive/stable disease underwent brain biopsy. In 66 patients Epstein-Barr virus (EBV)-DNA, JC virus (JCV)-DNA, and T gondii-DNA amplification was performed by PCR in CSF. Diagnostic criteria were histopathologic examination of bioptic or autoptic tissue specimens for all disorders and complete/partial resolution of FBL after empiric therapy for toxoplasmic encephalitis (TE). RESULTS: Neuroradiologic characteristics did not discriminate between TE and primary CNS lymphoma (PCNSL). Probability of TE was 0.87 in Toxoplasma-seropositive patients with mass effect who were not receiving anti-Toxoplasma prophylaxis, but only 0.59 if prophylaxis was performed. In seronegative patients with mass effect, the likelihood of PCNSL was 0.74. If EBV-DNA or T gondii-DNA tests were positive, the probability of PCNSL or TE increased to more than 0.96. The absence of T gondii-DNA did not exclude the possibility of a TE diagnosis. Among FBL without mass effect, the probability of progressive multifocal leukoencephalopathy (PML) was 0.81; this increased to 0.99 if JCV-DNA testing was positive. Sensitivity of brain biopsy was 93%, with a perioperative morbidity of 12% and a mortality of 2%. CONCLUSIONS: Due to the low diagnostic capability of clinical variables, PCR amplifications in CSF, especially for EBV-DNA and for JCV-DNA, represent, in most cases, an essential step in the differential diagnosis of AIDS-related FBL. This is particularly true in patients with FBL without mass effect or with mass effect and who are either seronegative or undergoing anti-Toxoplasma prophylaxis. Brain biopsy remains a necessary procedure in EBV-DNA-positive cases and in seronegative patients with FBL displaying a mass effect. Positive JCV-DNA testing may obviate the need for brain biopsy in patients with FBL without mass effect. An advanced diagnostic strategy based on combined clinical criteria and PCR tests may allow rapid and accurate identification of patients for prompt brain biopsy or specific therapy.

AIDS Dementia Complex↗
PubMed1996

A randomized trial (ISS 901) of switching to didanosine versus continued zidovudine after the diagnosis of AIDS.

Although the efficacy of switching from zidovudine (AZT) to didanosine (ddI) has already been evaluated in controlled studies, prior investigations were not specifically designed to evaluate this issue in patients with acquired immune deficiency syndrome (AIDS). This open, randomized, multicenter study (ISS 901) was designed to evaluate the clinical benefit in patients with AIDS of switching to ddI after 6-18 months of AZT and no major intolerance. Patients were randomized to continue AZT, maintaining the current dosage at randomization (n = 79), or to receive ddI (n = 80) at the dosage of 375 mg and 250 mg b.i.d. for body weight > 60 and < or = 60 kg, respectively. Primary efficacy measures were survival and time to new AIDS-defining events, analyzed by the intent-to-treat approach. The two groups were comparable for baseline characteristics, follow-up (15 months), and time spent on allocated treatment. At the end of the study, 104 patients (48 AZT, 56 ddI) had died and 90 had at least one new AIDS-defining event (44 AZT, 46 ddI). Kaplan-Meier estimates of survival and of time to first new AIDS-defining event showed no differences between the treatment groups. No differences were detected in other efficacy measurements (p24 antigenemia, CD4+ count, Karnofsky score, and body weight), occurrence of severe toxicities, and treatment modifications. Pancreatitis occurred only in ddI-treated patients (6%). In our population of patients with advanced disease, switching from AZT to ddI did not produce apparent benefits, suggesting that application of this strategy earlier in the course of human immunodeficiency virus disease should be considered.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation.

The prevalence of Mycobacterium tuberculosis (MTB) has increased worldwide, in part due to the HIV epidemic. Epidemiology data have demonstrated that HIV-infected individuals are more susceptible to MTB disease, which may lead to an acceleration in the progression of HIV disease. The purpose of this study was to determine whether MTB modulates HIV infection in vivo and to delineate the mechanisms involved by using in vitro model systems. Plasma viral load was measured in HIV-infected individuals before, during, and after the development of MTB disease; a 5- to 160-fold increase in viral replication was observed during the acute phase of MTB disease. In order to evaluate the mechanisms involved in this MTB-induced HIV replication, we used an in vitro system of primary PBMC and lymph node mononuclear cells isolated from HIV-infected individuals. The data demonstrated that MTB induced HIV replication in CD8+ T cell-depleted lymphocytes from HIV-infected individuals with a history of purified protein derivative (PPD) positivity but not in those who were PPD negative; this induction of HIV replication correlated with the level of cellular activation. In an in vitro acute HIV infection model, MTB increased HIV replication in PBMC from healthy donors with a history of PPD positivity, but not in PBMC from PPD-negative donors and this induction of viral replication also correlated with cellular activation. In conclusion, MTB increased HIV replication in vivo and in an in vitro model. This MTB-mediated viral production likely occurs through Ag-specific activation and infection of responding T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Predictors of Staphylococcus aureus pneumonia associated with human immunodeficiency virus infection.

This study is based on a retrospective logistic regression analysis of all human immunodeficiency virus (HIV)-infected patients with Staphylococcus aureus pneumonia (SAP) admitted to the Department of Infectious Diseases, Catholic University, Rome, Italy between January 1986 and December 1994. Nineteen patients with 24 episodes of SAP were enrolled in the study. A control group of 38 HIV-infected patients without pneumonia was included. The attack rate of SAP was 8.31/1000 HIV-related hospital admissions and the frequency, out of the total number of bacterial pneumonia observed in the study period, was 16% (24 of 154 patients). The large majority of SAP was community acquired. On the univariate analysis, intravenous drug abuse (IVDA) (P = 0.02), history of previous Pneumocystis carinii pneumonia (PCP) (P = 0.03) and cirrhosis (P = 0.03) were significant risk factors for SAP. In addition, IVDA and previous PCP were independent risk factors on multivariate analysis. All patients presented with fever associated with cough (74%), chest pain (26%) or shortness of breath (37%). Chest X-ray documented lobar pneumonia (78%), predominantly in the lower lobes, consolidation with cavitation (11%), and interstitial-nodular infiltrates (11%). Pleural effusion was present in 31% of patients. The response to therapy was favourable in 79% of patients. Recurrence occurred in 26% and death occurred in 21% of patients. Death was significantly associated with the low level (< 50 mm-3) of circulating T CD4+ cells (P = 0.03) and the recurrence of pneumonia (P = 0.03). In conclusion, the present study indicates that S. aureus is an important aetiologic agent of bacterial pneumonia in HIV-infected patients, especially if they are drug abusers with previous PCP.

Adolescent↗
PubMed1996

Analysis of the risk factors associated with the emergence of azole resistant oral candidosis in the course of HIV infection.

The objective of this case-control study, conducted in a large Italian university hospital over a 12-month period, was to evaluate the risk factors associated with the emergence of azole resistant oral candidosis in 64 Human Immunodeficiency Virus (HIV) infected patients. A swab was obtained from each patient by brushing candidal lesions. Candida albicans was isolated in 41 patients (64%), Candida glabrata in ten (16%), Candida krusei in five (8%), Candida kefyr in two (3%), Candida tropicalis in two (3%), and Candida lipolytica and Candida guilliermondii in one case, respectively. Two patients suffered a double infection i.e. C. albicans+C. krusei and C. albicans+C. glabrata, respectively. Candida species were tested in vitro for their susceptibility to ketoconazole, fluconazole, itraconazole and amphotericin B. MICs of the four antifungal drugs were obtained for each yeast using a microdilution broth method developed in our laboratory. Twenty four (37%) of the isolated strains were resistant both to itraconazole and fluconazole, five (8%) to fluconazole alone, and two (3%) to ketoconazole alone, while none of the isolated strains was resistant to amphotericin B. Patients with oral candidosis caused by a strain resistant to one or more azole drug were compared to control patients with azole-susceptible oral candidosis. On univariate analysis, more than five episodes of oral candidosis in the last year (P = 0.01), previous use of azole therapy (P = 0.001), C2-3 category of HIV infection (P = 0.01) and low number of circulating CD4+ T-cells (P = 0.03) were significantly associated with an increased risk for the development of azole resistance. However, previous use of azole therapy was the only factor selected by a stepwise logistic regression analysis which was independently associated with the isolation of azole resistant strains (P = 0.003). Our findings indicate that, in view of the potential risk for the emergence and selection of azole resistant strains of Candida in patients with AIDS, it is important to carefully choose the antifungal drug for the therapy of mild fungal infections after evaluation of the in-vitro susceptibility of the isolated strains.

AIDS-Related Opportunistic Infections↗
PubMed1995

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↗
PubMed1995

Evidence of a selective depletion of a CD16+ CD56+ CD8+ natural killer cell subset during HIV infection.

Three-color flow cytometric analysis of CD16+ natural killer (NK) cells was assessed in HIV seropositive patients and healthy heterosexual controls. A selective depletion of lymphocytes with the CD16+ NK phenotype was found among the HIV+ infected patients. When the CD16 lymphocyte subset was further evaluated by three-color flow cytometry, cells bearing both the CD8 and CD56 antigens were significantly decreased. Analysis of activation antigens revealed a large proportion of CD16+ NK cells from HIV+ patients expressed HLA-DR, but this did not correlate with CD25 (IL-2 receptor) expression. The overall loss of the CD8 and CD56 antigens among the NK population with an increase in activation status may be due to differential loss of the NK cell subsets or, alternatively, to the loss of immunoregulatory cytokines, which have been shown to be important in maintaining NK activity. Whether these changes in the NK compartment may influence the outcome of individuals with HIV disease still remains an open question but is an important issue when performing phenotypic analysis of HIV+ subjects.

CD4 Lymphocyte Count↗
PubMed1995

P-170 glycoprotein (P-170) is involved in the impairment of natural killer cell-mediated cytotoxicity in HIV+ patients.

In the present study we analyze peripheral blood lymphocytes (PBL) from patients with human immunodeficiency virus (HIV) infection for both phenotypic expression and function of P-glycoprotein (P-170). This transmembrane efflux pump is known to be one of the mechanisms responsible for the multidrug resistance (MDR) in cancer therapy and it is also constitutively expressed in normal PBL. P-170 function, evaluated as Rhodamine 123 (Rh123) efflux in flow cytometry, was found to be significantly reduced in CD16+ natural killer (NK) cells from patients with HIV infection. Interestingly, this reduced efflux significantly correlates with the decreased NK cytotoxicity observed in HIV+ patients, as evaluated against the NK-specific K562 target cell line. These results support a possible role of the P-170-related pump in specific immunological lymphocyte function such as NK cell-mediated cytotoxicity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

The impact of bacteraemia on HIV infection. Nine years experience in a large Italian university hospital.

The object of this case control study was to evaluate the frequency, the risk factors, the microbiological spectrum and the outcome of 249 cases of bacteraemia observed in 209 HIV-infected patients, most them affected by AIDS. The rate of bacteraemia in the total yearly HIV-related admissions increased from 4% in 1985 to 13% in 1993. The more common aetiological agents of bacteraemia were: Staphylococcus aureus (29.7%), non-typhoidal species of Salmonella (14.1%), Staphylococcus epidermidis (10.9%), Streptococcus pneumoniae (8.4%) and Pseudomonas aeruginosa (7.6%). A mixed flora was found in 14% of the episodes. Multivariate analysis of predisposing factors indicated that a low CD4+T-cell count (<0.2 x 10(9)/l) (P=0.01), use of central venous catheters (CVC) (P=0.01) and neutropenia (polymorphonuclear neutrophils <1.0 x 10(9)/l) (P=0.04) were independent risk factors for the development of bacteraemia. Logistic regression did not reveal any association of bacteraemia with intravenous drug abuse (on univariate analysis P=0.04). The response (31.8%). Recurrences to specific therapy was favourable in 170 episodes (68.2%); death occurred in 79 (31.8%). Recurrences arose in 40 patients, 17 (42.5%) of them died. The outcome of bacteraemia was influenced by a low number of CD4+T-cells (P<0.001) but not of polymorphonuclear cells. Our findings suggest that bacteraemia is a relatively common event in HIV-infected patients, especially under particular conditions (e.g. intravenous drug abuse, use of CVC, neutropenia and a low CD4-T-cell count). It requires special attention from physicians who must recognise and treat the condition promptly at an early stage.

AIDS-Related Opportunistic Infections↗
PubMed1995

Transmembrane P-glycoprotein (P-gp/P-170) in HIV infection: analysis of lymphocyte surface expression and drug-unrelated function.

P-glycoprotein (P-gp/P-170), a transmembrane efflux pump known to be one of the mechanisms responsible for multidrug resistance in cancer therapy, is constitutively expressed in several solid human tissues as well as in normal peripheral blood lymphocytes and bone marrow cells. In particular, this molecule has been associated with the transport of perforin and other cytolysins in natural killer (NK) and T cytotoxic lymphocytes. In the present study, we analyzed peripheral blood lymphocytes (PBLs) from controls and HIV+ patients for phenotypic expression and function of the P-gp/P-170 molecule. We found that 90% of all PBL subsets (i.e., CD4+, CD8+, CD56+, and CD19+ cells) expressed surface P-gp/P-170 both in controls and HIV+ patients. However, a significant decrease in CD4+/P-170+ and CD19+/P-170+ cells was observed in HIV+ individuals with respect to controls. PHA and IL-2 stimulation of PBLs was unable to increase the expression of P-gp/P-170 both in controls and HIV+ patients, despite the increased detection of the CD25 molecule. On the other hand, stimulation with anti-CD3 determined a significant increase in lymphocyte P-gp/P-170. The function of P-gp/P-170, assessed by a flow cytometric assay for rhodamine-123 (Rh123) efflux, was significantly reduced in CD16+ NK cells and CD19+ B cells from HIV+ patients. The Rh123 efflux by NK cells correlated (p < 0.01) with the NK cytotoxicity against the 51Cr-labeled K562 cell line. Last, the effect of the antiretroviral drugs AZT, ddI, and ddC on P-gp expression and function was evaluated. The dideoxynucleoside compounds did not inhibit P-gp/P-170 function of normal mononuclear cells in vitro, and did not increase P-gp/P-170 expression in vivo, in patients undergoing antiretroviral therapy with AZT. These findings provide further evidence of a possible involvement of the P-gp/P-170 system in specific immunological lymphocyte functions, and especially in cytotoxic-type functions. In addition, it is possible to suggest, on the basis of our experimental data, that the dideoxynucleoside class of antiretroviral agents does not contribute to the phenotypic and functional alterations related to P-glycoprotein during HIV infection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Evaluation of cerebrospinal fluid EBV-DNA and IL-10 as markers for in vivo diagnosis of AIDS-related primary central nervous system lymphoma.

Acquired immunodeficiency syndrome (AIDS)-related primary central nervous system lymphoma (PCNSL) is almost always associated with the Epstein-Barr virus (EBV), and EBV-DNA in cerebrospinal fluid (CSF) has been indicated as a useful tumour marker for this HIV-related neoplasm. AIDS lymphomas also show an enhanced production of IL-10 which is generally associated with the presence of EBV in lymphoma cells. We performed a prospective study in 19 HIV seropositive patients with brain mass lesions, and in 21 other AIDS patients with or without other neurological disorders, to assess the in vivo diagnostic value of EBV-DNA and of IL-10 levels in the CSF for primary lymphoma of the central nervous system (CNS). EBV-DNA was detected by a nested polymerase chain reaction (PCR) in the CSF from seven of eight patients with PCNSL, diagnosed by brain biopsy (87.5% sensitivity) and in none of the 11 controls with brain mass lesions (100% specificity) and of the other 21 AIDS patients with or without neurological disorders. The only patient with PCNSL without detectable EBV-DNA in the CSF was also negative for EBV-DNA in the lymphoma tissue, whereas the samples of the other seven brain lymphomas were all positive for EBV-DNA by nested PCR. Therefore 100% of patients with an EBV-positive primary CNS lymphoma had detectable EBV-DNA in the CSF. No patient from the control group without PCNSL with EBV-negative CSF developed a lymphoma after a mean follow-up of 157 +/- 173 d. IL-10 levels in the CSF from the patients with PCNSL were not significantly different from those in the other groups of patients with AIDS. Due to uniformly high levels in the CSF from AIDS patients, IL-10 is not a useful diagnostic marker for AIDS-related brain lymphoma. The detection of EBV-DNA from the CSF by nested PCR is an extremely sensitive and specific diagnostic tool for AIDS-related PCNSL and should be further evaluated as a possible alternative in patients from whom brain biopsy is not advisable.

Adult↗
PubMed1995

Clostridium difficile-associated diarrhoea in patients with human immunodeficiency virus infection: a case-control study.

OBJECTIVE: To evaluate the prevalence of, risk factors for, treatment and outcome of Clostridium difficile-associated diarrhoea (CDAD) in patients with human immunodeficiency virus (HIV) infection. DESIGN: A prospective case-control study, conducted between January 1992 and April 1994. SETTING: Department of Infectious Diseases in a large university hospital with HIV in- and out-patient units. PATIENTS AND METHODS: The study included 124 patients grouped as follows: 31 HIV-infected patients with CDAD (group A); 31 HIV-seronegative patients with CDAD (group B) and 62 HIV-infected patients without CDAD (group C). The patients in group B and C were selected randomly during the study period. RESULTS: The prevalence of CDAD in HIV-infected patients was 3.1% compared with 1.6% in HIV-seronegative patients (P = 0.02). On univariate analysis, the predisposing factors in group A were antibiotic use in the 4 weeks prior to the onset of CDAD (P = 0.03 versus group C), prolonged hospitalization (over 20 days; P = 0.04), low levels of circulating CD4+ cells (P = 0.03) and use of antacids (P = 0.04). The antibiotics significantly associated with CDAD were trimethoprim-sulfamethoxazole (P = 0.02 versus group C), third generation cephalosporins (P = 0.03) and clindamycin (P = 0.03). On multivariate analysis of the risk factors, the use of antibiotics was the sole independent risk factor for CDAD (P = 0.03). The clinical symptoms of CDAD were more severe in HIV-infected patients than in controls. Three patients in group A (9.7%) had one relapse and one patient (3.2%) experienced chronic diarrhoea. The outcome of CDAD was not influenced by the number of circulating polymorphonuclear cells and CD4+ cells. No difference in the survival curves of AIDS patients with or without CDAD, stratified according to age, sex and CD4+ cell count was observed. CONCLUSIONS: Our data suggest that CDAD is more common in HIV-infected patients, particularly those receiving antibiotic therapy, than in HIV-seronegative patients. Since C. difficile can cause severe and recurrent or chronic infections in HIV-infected patients, CDAD must be always considered in the differential diagnosis of diarrhoea in patients with AIDS and AIDS-related conditions.

AIDS-Related Opportunistic Infections↗