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Biomedical subjects

R Cauda

Publications and source records attributed to R Cauda.

At least 73 records · Page 4Linked to original sources
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

Pott's disease of the cervico-occipital junction in an AIDS patient.

Pott's disease of the cervical spine is relatively rare despite the fact that tuberculous spondylitis is still the most common manifestation of bone and joint infection. We describe a case, the first to our knowledge, of sub-occipital Pott's disease associated with a retropharyngeal abscess in an acquired immune deficiency syndrome (AIDS) patient. Neurological signs were the main clinical findings. The patient was successfully treated with anti-tuberculosis drugs combined with external stabilization of the spine.

AIDS-Related Opportunistic Infections↗
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

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

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↗