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Biomedical subjects

R Cauda

Publications and source records attributed to R Cauda.

At least 37 records · Page 2Linked to original sources
PubMed1999

Non-AIDS-defining neoplasms and HIV infection.

The purpose of this study was to characterise the epidemiological and the clinical features of non-AIDS-defining neoplasms (NAN) in HIV-infected subjects in the era of highly active antiretroviral therapy (HAART). A retrospective cohort of 4,041 subjects was established. Patients were recruited from January 1989 to December 1998. We observed 51 NAN over the study period. The overall incidence rate was 0.21 per 100 person-years (PY) and it remained stable, also after the introduction, in 1996 of HAART. Moreover, stratifying according to the type of neoplasms there was no statistically significant difference in the incidence of NAN over the study period. While the epidemiological features of NAN generally was not different from that observed in immunocompetent individuals, the neoplasms had a more aggressive clinical course and a poor prognosis. Survival analysis showed that the presence of NAN significantly reduced the survival of patients with AIDS (P=0.01; OR=0.62; 95% CI=0.47-0.96) compared with matched controls. The overall mortality-rate was 63% with an incidence rate of 0.13 per 100 PY. Although the incidence rate of NAN is not of great magnitude, as the number of HIV-infected individuals continues to increase and their survival improves, the number of HIV-infected subjects with NAN might consequently increase as well as the related morbidity and mortality.

Adult↗
PubMed1998

Nosocomial bloodstream infections in HIV-infected patients: attributable mortality and extension of hospital stay.

A 3-year prospective matched case-control study was performed to investigate the potential risk factors, prognostic indicators, extension of hospital stay, and attributable mortality of nosocomial bloodstream infections in HIV-infected patients. Matching variables were: age, gender, number of circulating CD4+ T lymphocytes, cause of hospital admission, hospitalization in the same ward within the 6 weeks of diagnosis of the case, and length of stay before the day of infection in the case. Eighty-four cases and 168 matched controls were studied. Nosocomial bloodstream infections complicated about 3 of 1000 hospital days per patient in the study period. With step-wise logistic regression analysis, the most important predictors for developing nosocomial bloodstream infections were: increasing value of Acute Physiology and Chronic Health Evaluation (APACHE II) score (p = .001) and use of central venous catheter (CVC) (p = .002). The excess of hospital stay attributable to nosocomial bloodstream infections was 17 days. The crude mortality rate was 43%. The attributable mortality rate was estimated to be 27% (95% confidence interval [CI] = 13%-48%). The estimated risk ratio for death was 3.91 (95% CI = 2.06-7.44). Multivariate analysis identified two prognostic indicators that were significantly associated with unfavorable outcome of bloodstream infections: number of circulating CD4+ T cells <100/mm3 (p = .002) and APACHE II score >15 (p = .01). Nosocomial bloodstream infections are more common in patients with advanced HIV disease. Important cofactors are high APACHE II score and use of CVC. These infections can cause an excess mortality and significantly prolong the hospital stay of HIV-infected patients.

Adult↗
PubMed1998

The role of oxidative imbalance in progression to AIDS: effect of the thiol supplier N-acetylcysteine.

In this study we investigate the redox profile of HIV+ patients at different stages of disease with regard to immunological parameters, i.e., the number of circulating CD4+ and CD8+ lymphocytes. For this purpose, peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, HIV+ patients in the asymptomatic phase, long-term nonProgressors (LTNPs), and AIDS patients have been considered. Cells have been exposed in vitro to the prooxidizing agent menadione, which is able to induce superoxide anion formation, and the susceptibility of the cells to the induced oxidative stress was estimated. Moreover, the possibility that the susceptibility of the cells to oxidative stress might be reduced by preexposing them to the antioxidizing agent N-acetylcysteine (NAC) has also been analyzed. The results obtained can be summarized as follows: (1) treatment with the prooxidant agent is capable of inducing massive morphological alterations in PBMCs. In particular, a significant correlation was found between the decrease in number of CD4+ lymphocytes in patients at different stages of disease and the susceptibility of their PBMCs to oxidative stress; (2) preincubation with NAC was able to preserve partially the ultrastructural characteristics of PBMCs isolated from HIV+ patients. In particular, a direct relationship was found between the efficacy of NAC protection and CD4 counts; (3) evaluation of the plasma index of peroxidation and the number of circulating CD4 lymphocytes indicates the existence of a positive correlation between "systemic" oxidative imbalance and stage of the disease; and (4) cells from LTNPs display either oxidative susceptibility or oxidative markers similar to those of healthy donor cells. Our study suggests that the redox profile of patients may be considered a predictive marker of AIDS progression and that the acute infection and the asymptomatic phase of the disease may represent a useful period in which the combined use of antiretroviral and antioxidant drugs may be beneficial.

Acetylcysteine↗
PubMed1998

Bacterial pneumonia in HIV-infected patients: analysis of risk factors and prognostic indicators.

This case control study assessed risk factors and prognostic indicators of 350 episodes of bacterial pneumonia in 285 HIV-infected patients. On univariate analysis, intravenous drug abuse (i.v.DA; p < .001 versus controls), regular cigarette smoking (p < .001), cirrhosis (p = .04), and history of a previous episode of pneumonia (p = .04) were risk factors for community-acquired episodes of bacterial pneumonia, whereas length of hospitalization (p = .01) was a risk factor only for nosocomial bacterial pneumonia. The small amount of circulating T CD4+ cells (<100/ mm3) was a risk factor in both groups of pneumonia (p < .05). Stepwise logistic regression analysis revealed that i.v.DA in community-acquired episodes and low levels of circulating T CD4+ cells, both in community-acquired and hospital-acquired episodes, were independent risk factors for the development of bacterial pneumonia. The case-fatality rate observed in our study was 27%. On stepwise logistic regression analysis, T CD4+ cell counts < or = 100/mm3 (p = .02), neutropenia (p = .04), PO2 arterial level < or = 70 mm Hg (p = .01), and Karnofsky score < or = 50 (p = .04) were independent indicators of mortality. According to a personally developed prognostic score, 211 episodes of pneumonia (60%) were classified as mild, 63 (18%) as moderate, and 76 (22%) as severe. Clinicians must carefully evaluate those variables that can influence the prognosis of bacterial pneumonia to make early identification of affected patients and to promptly establish the most appropriate therapeutic strategy in each case.

AIDS-Related Opportunistic Infections↗
PubMed1998

A new, striking morphological alteration of P-glycoprotein expression in NK cells from AIDS patients.

Natural killer cells from healthy donors express P-glycoprotein on their surface. This molecule is rearranged during the process of cell-mediated cytotoxicity and it appears to be clustered in the cell-to-cell contact regions. By contrast, in HIV-infected subjects this rearrangement is hindered. These results seem to be associated with cytoskeleton network alterations of the cell-mediated killing process occurring in AIDS patients and can contribute to the comprehension of the mechanisms of the natural killer cell deficiency found in these patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Flow cytometric detection of perforin in normal human lymphocyte subpopulations defined by expression of activation/differentiation antigens.

We investigated with three-color flow cytometry the expression of perforin (Pf) in normal human lymphocyte subpopulations identified by means of activation and differentiation-related antigens. Interestingly, Pf could be detected in a substantial subset (13 +/- 2%) of memory CD4+ CD45RO+ cells, on relevant percentages of memory (CD45RO+) and naive (CD45RA+) CD8+ cells and on virtually all CD3- CD16+, CD3- CD56+ and NKB1+ natural killer cells, as expected. The analysis of fluorescence intensity showed higher levels of Pf expression on CD8dim and NK cells compared to CD8bright and CD4+ lymphocytes, Pf and CD69, HLA-DR, CD95 and CD25 activation/differentiation-related antigens were never co-expressed. On average, 15 +/- 3% of CD3+ CD28+ cells were found to be Pf+, in line with a previously activated or memory cell type. Comparable percentages of CD8+ CD11b- (cytotoxic) and CD8+ CD11b+ (suppressor) T cells were Pf+. Multiparameter flow cytometry is a powerful tool to detect minute fractions of Pf-expressing cells in heterogeneous populations.

Biomarkers↗
PubMed1998

Intracellular expression of P-170 glycoprotein in peripheral blood mononuclear cell subsets from healthy donors and HIV-infected patients.

BACKGROUND AND OBJECTIVE: P-glycoprotein (P-gp) is a transmembrane efflux pump that actively extrude a variety of unrelated drugs from cancer cells, leading to the so-called multidrug resistance (MDR) phenomenon. However, P-gp has also been found in normal bone marrow and peripheral blood mononuclear cells (PBMC). Recently, the presence of P-glycoprotein in PBMC from human immunodeficiency virus (HIV)-infected patients has also been investigated and a phenotype-associated P-gp expression has been detected. DESIGN AND METHODS: A total of thirty-eight HIV-1 positive patients with a mean age of 34 years (range, 24-41 years) were studied after an informed consent. Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation on a Ficoll/Hypaque and P-glycoprotein expression was investigated on lymphocyte population by single and double-color immunofluorescence techniques. We investigated: i) both surface and intracellular expression of the P-gp molecule in different PBMC subsets, ii) P-gp expression modifications occurring during HIV infection, and iii) the effect of HIV-gp120 on the expression of P-gp by T lymphocyte subsets from healthy donors. RESULTS: Our experimental findings indicate that: a) P-gp glycoprotein can be detected on an intracellular level in different PBMC subpopulations (mainly CD8+ T lymphocytes, CD16+ NK cells and CD14+ monocytes); b) this intracellular expression is decreased in specific PBMC subsets (i.e. T-CD8+ and NK-CD16+) from HIV-infected patients and c) a rearrangement was obtained when CD4+ and CD8+ lymphocytes from healthy donors were exposed in vitro to the HIV-binding glycoprotein gp120. INTERPRETATION AND CONCLUSIONS: Our results indicate that P-gp glycoprotein can also be expressed intracellularly and can be rearranged in PBMC subsets from HIV-infected patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Risk factors, nutritional status, and quality of life in HIV-infected patients with enteric salmonellosis.

AIMS: To define the potential risk factors, prognostic indicators, and quality of life of HIV-infected patients with enteric salmonellosis. METHODS: A five-year matched (1:2) case-control study was performed. Thirty cases and 60 matched controls were studied. RESULTS: Univariate analysis (p < 0.05) identified six risk factors for enteric salmonellosis: 1) increasing value of APACHE II score, 2) altered nutritional status, 3) previous antibiotic therapy, 4) ingestion of "risk" foods, 5) multiple (> or = 2) previous opportunistic infections, 6) stage C of HIV infection. Using the multivariate analysis, the most powerful predictors for developing an enteric salmonellosis were: increasing value of APACHE II score and altered nutritional status. The response to therapy was favourable in all episodes. Five (17%) patients suffered from one or more relapses. Multivariate analysis identified that a low number of circulating CD4+ (< 100/mm3) and a high APACHE II score (> 15) predict an increased risk of relapses. CONCLUSIONS: HIV-associated enteric salmonellosis occurs more frequently in patients with advanced stage of HIV infection and with impaired nutritional status. We stress the need for a prompt and accurate diagnosis and treatment since the possible haematogenous spread and relapses appear reduced under early and prolonged antibiotic therapy.

AIDS-Related Opportunistic Infections↗
PubMed1998

Serum of healthy donors receiving granulocyte colony-stimulating factor induces T cell unresponsiveness.

The effects of serum from healthy donors receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF) (G-serum) on blast transformation, expression of activation-related antigens, secretion of interleukin (IL)-2, and proliferation were evaluated in allogeneic lymphocytes stimulated with phytohemagglutinin. Escalating concentrations of G-serum induced 27%, 47%, and 70% suppression of lymphocyte proliferation; interestingly, CD4+ and CD8+ cells underwent blast transformation and up regulated early (CD69) and late (CD25, HLA-DR, and CD71) activation-related antigens. Negligible fractions of apoptotic cells were found after mitogenic challenge, suggesting that the strongly diminished proliferation was not attributable to extensive activation-induced programmed cell death of responding T cells. The levels of IL-2 in cultures containing G-serum were comparable to those in cultures performed without G-serum; however, high concentrations of exogenous IL-2 restored lymphocyte mitogenesis regardless of G-serum concentration. These findings--cell enlargement, upregulation of activation-related antigens, inability to proliferate after mitogenic stimulus, and restoration of cell division by exogenous IL-2--resembled those associated with "partial activation" of lymphocytes, a fundamental control mechanism of tolerance induction in T cell clones. Soluble immunoregulatory mediators infused with allogeneic hematopoietic progenitor products collected after rhG-CSF administration could induce T cell unresponsiveness in vivo, thus preventing clonal expansion and amplification of immune responses, and could account for the unexpectedly reduced incidence and severity of graft vs. host disease compared with allogeneic marrow infusion.

Adult↗
PubMed1997

Central venous catheter-related sepsis in a cohort of 366 hospitalised patients.

Five hundred two central venous catheters inserted in 366 patients were evaluated prospectively over a one-year period to determine the frequency and risk factors associated with catheter-related sepsis. For study purposes, in cases in which catheter infection was suspected but the initial blood cultures were negative, the catheters were replaced by guidewire technique; otherwise, the catheters were routinely changed after 21 days by guidewire technique. A catheter-related infection was suspected in 190 cases (190/502, 38%). A diagnosis of catheter-related sepsis was established in 50 patients, which represents 10% of the total number of lines (502). Over a total of 6428 days of catheter use, the infection rate was 0.8 cases of sepsis per 100 catheter-days. Staphylococcus epidermidis, Staphylococcus aureus, and Candida spp. were the most frequently isolated aetiological agents of sepsis. On univariate analysis, six variables affecting the rate of catheter-related sepsis were identified: neutropenia for more than eight days (p < 0.001); AIDS (p < 0.001); haematological malignancy (p < 0.001); administration of total parenteral nutrition (p = 0.001); duration of site use (p = 0.04); and high APACHE II score (p = 0.04). The logistic regression analysis revealed that AIDS and haematological malignancies were independent risk factors of catheter-related sepsis. Catheter replacement over a guidewire was no more likely to be associated with sepsis than was percutaneous catheter insertion. In conclusion, although the incidence of established catheter infection is much lower than the incidence of suspected infection, in most cases of suspected infection it is wise to change the catheter with the guidewire technique and wait for culture of the tip, rather than to remove the catheter immediately. Such a policy may help reduce the number of unnecessary catheter removals.

APACHE↗
PubMed1997

Comparative analysis of prognostic indicators of aspergillosis in haematological malignancies and HIV infection.

The objective of this study was to identify the prognostic factors influencing the outcome of aspergillosis in two models of immunodeficiency, namely haematological malignancies and HIV infection. The study is based on a 5 year prospective logistic regression analysis of risk factors, clinical features, radiological findings and therapy affecting the prognosis of aspergillosis in 43 patients, i.e. 27 haematological neoplastic patients (group A) and 16 HIV infected patients (group B). Univariate analysis indicated that neutropenia (P = 0.02), haemoptysis (P = 0.03) and concomitant AIDS (P = 0.02), negatively influenced the prognosis of aspergillosis. Comparing the two groups of patients, significant differences emerged in the prognostic indicators. In particular respiratory failure (P = 0.02) and radiological bilateral involvement of the lungs were associated with a poor prognosis in group A (P = 0.04) and low (2100/mm3) T CD4+ cell count in group B (P = 0.02). At variance, a better prognosis was documented in patients treated with sequential therapy (amphotericin B and itraconazole) only within the group of haematological patients (P = 0.003). On multivariate analysis sequential therapy (P = 0.01) and AIDS (P = 0.03) were independent prognostic indicators of aspergillosis. In conclusion, our prospective study indicates that aspergillosis, although an uncommon event in patients with HIV infection, has a more severe prognosis in comparison to haematological patients. Future prospective clinical trials are necessary to confirm the real importance of the sequential therapy, with amphotericin B and itraconazole, in patients with aspergillosis.

Adult↗
PubMed1997

Gastric cryptosporidiosis complicating HIV infection: case report and review of the literature.

Gastric cryptosporidiosis is rarely reported despite the fact that Cryptosporidium has been recognized with increasing frequency as an aetiological agent of severe chronic diarrhoeal enteritis in patients with human immunodeficiency virus (HIV) infection. We report a case of gastric cryptosporidiosis that occurred in an AIDS patient. Fifteen previously reported cases of gastric cryptosporidiosis are also reviewed. The review of all cases reported in the literature, including our own, showed that 12 patients had digestive symptoms. In 14 out of 16 patients the diagnosis was achieved by biopsy of the gastric mucosa rather than by examination of the stools. Gastric localization of Cryptosporidium is a rare and severe manifestation of intestinal cryptosporidiosis in patients with AIDS, and no single drug regimen has yet been found to be effective in eradicating this organism.

AIDS-Related Opportunistic Infections↗