PubMed HealthSearch

Biomedical subjects

A Lazzarin

Publications and source records attributed to A Lazzarin.

At least 19 recordsLinked to original sources

Parenteral and sexual transmission of human immunodeficiency virus in intravenous drug users: a study of seroconversion. The Northern Italian Seronegative Drug Addicts (NISDA) Study.

To evaluate the role of parenteral and sexual transmission of human immunodeficiency virus, we studied seronegative intravenous drug users recruited from 25 drug dependence treatment centers in northern Italy. All attending intravenous drug users were asked for their consent and screened for antibodies to human immunodeficiency virus; those who were seronegative were enrolled, interviewed about their habits, and invited to follow-up visits. Between 1987 and 1989, 1,195 seronegative intravenous drug users were enrolled, 635 were followed up (mean duration, 11.9 months), and 35 seroconversions were observed. The incidence rate ratios were 3.3 (95% confidence interval (CI) 1.4-7.5) for subjects aged less than 20 years, 2.4 (95% CI 1.2-4.7) for less than 2 years of intravenous drug use, 2.2 (95% CI 0.9-5.5) for syringe sharing, and 1.0 for subjects with a sexual partner who had tested positive for human immunodeficiency virus. A case-control approach, using logistic regression and adjusting for sex, age, area, and prevalence, showed odds ratios of 13.2 (95% CI 3.1-56.8) for frequent syringe sharing and 4.0 (95% CI 1.5-10.4) for sexual contacts with seropositive partners; frequent use of condoms was associated with a reduction in risk that did not reach statistical significance. Parenteral transmission is the most important route of infection with the human immunodeficiency virus among intravenous drug users, and sexual transmission plays a relevant, additive role.

Adult

Monocyte-derived macrophage function in HIV-infected subjects: in vitro modulation by rIFN-gamma and rGM-CSF.

We investigated monocyte-derived macrophage function in 25 HIV-positive patients, 19 in the CDC class III and 6 class IV; 17 were intravenous drug abusers (IVDA) and 8 were homosexual men. Macrophages from HIV-positive patients behaved normally in assays of superoxide anion (O2-) production and candidacidal activity. After 3 days' treatment with 200 U/ml recombinant interferon-gamma (rIFN-gamma) or 250 U/ml recombinant granulocyte/macrophage-colony stimulating factor (rGM-CSF), both control and HIV-positive patients' phagocytes expressed the activated state, as indicated by the increased O2- production in response to phagocytable or soluble stimuli; however, these cytokines did not enhance candidacidal activity. Compared to appropriate HIV-negative controls (18 healthy heterosexuals, 4 homosexuals and 4 IVDA), macrophages from 19 of the 25 HIV-positive patients presented a significant defect in their Fc receptor (FcR)-dependent phagocytosis, independently from the CDC stage, AZT therapy, or life style. Treatment of macrophages with rIFN-gamma impaired their capacity to ingest IgG-coated erythrocytes, both in controls and HIV-positive subjects. Treatment of phagocytes with rGM-CSF significantly increased their FcR-dependent phagocytosis in controls, whereas in HIV-positive patients and in HIV-negative homosexuals and IVDA only an upward tendency was observed. Although the mechanism of the impaired FcR-dependent phagocytosis in HIV-positive patients remain to be clarified, our results suggest that this functional defect may be secondary to phagocyte priming by circulating IFN-gamma in vivo. This macrophage alteration may be implicated in the immunodeficiency of HIV-positive patients. However, considering the potential role of FcRs in HIV infection enhancement, the defective FcR function might even be a protective mechanism against FcR-mediated HIV dissemination. In the light of these findings, the immunotherapeutic potential of IFN-gamma and GM-CSF in HIV infection merits further investigation.

Acquired Immunodeficiency Syndrome

Mediator release in cerebrospinal fluid of human immunodeficiency virus-positive patients with central nervous system involvement.

In this study we evaluated the release of some mediators of inflammatory reactions such as histamine (H), leukotriene B4 (LTB4), leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in the cerebrospinal fluid (CSF) of 15 patients with acquired immunodeficiency syndrome (AIDS), eight with opportunistic infections of the central nervous system (CNS) and seven without HIV-related neurological pathology, and of 25 HIV-negative control subjects with other neurological diseases. The cerebrospinal LTB4 level was increased in all the AIDS patients (mean 348 pg/ml); the control group revealed normal levels of LTB4 in the CSF (mean 63.2 pg/ml). The PGD2 level in the HIV-positive (mean 264 pg/ml) patients was higher than of the control subjects (mean 50 pg/ml), while low LTC4 levels were found both in the HIV-positive and control groups. We did not find any significant concentration of H in the CSF of either the HIV-positive or the control subjects. These findings may be due to the presence of chronic HIV infection or to the opportunistic infections of the CNS that so often occur in the latest stages of the disease.

Brain Diseases

Mother-to-child transmission of hepatitis C virus detected by nested polymerase chain reaction.

Serum samples from eight pregnant women and their offspring were studied by nested polymerase chain reaction (PCR) for detection of hepatitis C virus (HCV) RNA to evaluate mother-to-child transmission of this virus. The mothers were all infected with human immunodeficiency virus (HIV); none showed symptoms of HCV infection. Anti-HCV antibodies were tested for by recombinant immunoblot assay. HCV viral sequences were found in five of the mothers and four of eight children, three of them at birth. Viremia was persistent in one infant who had chronic transaminase elevation and persistently remained anti-HCV-positive. The other three babies had intermittent viremia; all were asymptomatic and lost anti-HCV antibodies during follow-up. This loss of antibodies was also observed in PCR-negative infants. Thus, these results demonstrate transmission of HCV from mother to child by women coinfected with HCV and HIV. They indicate the usefulness of PCR for direct and early detection of HCV viremia in neonates.

Base Sequence

Cytomegalovirus infection of the central nervous system in patients with AIDS: diagnosis by DNA amplification from cerebrospinal fluid.

A nested polymerase chain reaction (PCR) was evaluated for the detection of cytomegalovirus (CMV) DNA in cerebrospinal fluid (CSF). CSF and serum samples from 19 AIDS patients with intracerebral CMV infection diagnosed at autopsy were retrospectively examined. As controls, CSF and serum samples from 15 AIDS patients with only extracerebral CMV involvement at autopsy, from 10 AIDS patients without CMV infection at autopsy, and from 10 anti-human immunodeficiency virus-negative patients without ongoing CMV infection, were studied. CMV DNA was detected from patients with intracerebral CMV infection in 9 of 9, 5 of 6, and 1 of 4 CSF samples collected, respectively, 1-30, 30-90, and 90-300 days before death. Twelve of 13 sera from these patients were CMV PCR-positive. None of the control patients had CMV DNA in CSF. PCR was positive in 6 of 8 sera from AIDS patients with only extracerebral CMV infection and in serum from 1 AIDS patient without CMV involvement at autopsy. CMV PCR on CSF is highly sensitive and specific. It should be considered a rapid and reliable diagnostic method for CMV infection of the central nervous system.

AIDS-Related Opportunistic Infections

AIDS-defining diseases in 250 HIV-infected patients; a comparative study of clinical and autopsy diagnoses.

OBJECTIVE: To evaluate the correlation between clinical and autopsy findings in 250 AIDS patients. METHODS: Clinical and autopsy diagnoses of AIDS-defining diseases in 250 AIDS patients who died in Milan between May 1984 and February 1991 were compared. RESULTS: Pneumocystis carinii (PCP) and oesophageal candidiasis were the most frequent clinical diagnoses, while cytomegalovirus (CMV) infection was observed in almost half of the autopsies. Forty-seven per cent of the diseases found at autopsy had not been diagnosed during life; CMV infection, mycoses, HIV-specific brain lesions, cerebral lymphomas and progressive multifocal leukoencephalopathy (PML) had a higher rate of non-diagnosis in life. CMV visceral infection accounted for the majority of the diseases not recognized in life. In contrast, clinically diagnosed PCP, oesophageal candidiasis and, to a lesser degree, brain toxoplasmosis were often not found at autopsy, possibly indicating a significant rate of recovery and prevention of relapse. Finally, bacterial pneumonia and sepsis, although not AIDS indicator diseases, were observed in approximately one-third of the autopsies. CONCLUSION: Considerable differences in the frequency and type of the AIDS-defining diseases diagnosed during life and at post mortem were found.

AIDS-Related Opportunistic Infections

HLA-associated susceptibility to HIV-1 infection.

We studied HLA antigen distribution of 50 heterosexual partners of HIV+ drug abusers with more than 1 year of sexual exposure to HIV, 36 children born to seropositive mothers and 61 haemophiliac patients exposed to presumably infectious clotting factor concentrates. B52 and B44 antigens were associated with HIV resistance while B51 was associated with HIV susceptibility. Forty-nine HIV+ drug abusers, spouses of heterosexual partners studied and 25 HIV+ mothers of the children were also typed. DR11 phenotype was associated with infectiousness of HIV+ subjects. Our data suggest that the HLA region controls susceptibility to infection with HIV and infectiousness of HIV+ subjects in different risk groups.

Acquired Immunodeficiency Syndrome

Membrane expression and function of complement receptors CR1 and CR3 on neutrophils from HIV-infected subjects: modulation by rTNF-alpha and rGM-CSF.

We evaluated membrane expression and function of complement receptors CR1 and CR3 on neutrophils from 27 HIV-positive (HIV+) subjects (14 in the CDC class III and 13 class IV) as well as their modulation in vitro by recombinant tumour necrosis factor-alpha (rTNF-alpha) and granulocyte-macrophage colony stimulating factor (rGM-CSF). While CR1 was expressed at similar levels on neutrophils from controls and HIV+ subjects, CR3 expression was significantly higher in CDC class IV subjects than in healthy controls. CR1 and CR3 expression was significantly increased after treatment of neutrophils with both cytokines, without differences between controls and HIV+ subjects. Similarly, the superoxide anion (O2-) production in response to C3-coated zymosan (C3zy) was significantly enhanced on neutrophils from CDC class IV subjects when compared with controls. rGM-CSF and rTNF-alpha treatment significantly enhanced the spontaneous as well as C3zy-stimulated O2- production by neutrophils from controls and CDC class III subjects, and induced an upward trend in the CDC class IV group. These results indicate that the neutrophils of HIV+ patients are preactivated in vivo but they also indicate that these cells may correctly respond to a subsequent particulate stimulus as well as to activating cytokines. Our findings suggest that desensitization or functional exhaustion of complement receptors are not implicated in the abnormalities observed on neutrophils from HIV+ patients.

Adult

Incidence and prevalence trends of HIV infection in intravenous drug users attending treatment centers in Milan and northern Italy, 1986-1990.

To assess the incidence and time trends of human immunodeficiency virus (HIV) infection among intravenous drug users (IVDUs) and to evaluate the opportunities for prevention, we studied IVDUs recruited from 23 drug dependence treatment centers in Milan and Northern Italy. Participants were screened for HIV antibodies, and seronegative subjects were enrolled. A preventive intervention, based on counseling and HIV antibody testing, was done, and participants were invited to the centers for follow-up visits. We enrolled 1,532 subjects between 1 January 1987 and 31 October 1990, and we observed 901 subjects for an average of 15.9 months. Forty-one cases of HIV infection occurred, giving a seroconversion rate of 6.1% in 1987, 4.1% in 1988, 2.2% in 1989, and 1.6% in 1990. HIV prevalence decreased from 54% in 1986 to 49% in 1989. Incidence rates were higher in areas with high prevalence. During follow-up, 35 to 55% of the subjects stopped injecting heroin intravenously altogether, and those who did not stop decreased the frequency of syringe sharing. This is probably the reason for the decline in seroconversion rates, while the apparent decline in prevalence may be due to the entry of new seronegative individuals and/or to differential withdrawal of HIV-positive individuals from the IVDU population to the heterosexual (non-IVDU) population.

Adult

A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia.

BACKGROUND: Current recommendations for prophylaxis of Pneumocystis carinii pneumonia (PCP) are based on data from patients who have had at least one episode of PCP (secondary prevention). We designed a study to determine the efficacy and side effects of inhaled pentamidine in the primary prevention of PCP. METHODS: Two hundred twenty-three patients sero-positive for human immunodeficiency virus (HIV) who had the acquired immunodeficiency syndrome (AIDS) but not PCP, who had advanced AIDS-related complex, or who had less than 0.2 x 10(9) CD4-positive lymphocytes per liter received either 300 mg of pentamidine isethionate or 300 mg of sodium isethionate every 28 days by inhaler. The proportion of patients surviving without PCP was analyzed with the log-rank test as a function of time spent in the trial, according to the intention to treat with either placebo or pentamidine. RESULTS: The third of five planned interim analyses showed a significant difference in the occurrence of PCP, with 8 cases in pentamidine group and 23 in the placebo group (nominal P value = 0.0021). There were no deaths within 60 days of the diagnosis of PCP and no significant differences in survival between groups. Approximately 53 inhalations were needed to prevent one episode of pneumonia. Thirty-eight of 114 patients given pentamidine (33 percent) and 7 of 109 given placebo (6 percent) had moderate-to-severe coughing during inhalations (two-tailed P less than 0.00001), which caused 4 patients given pentamidine (3.5 percent) to discontinue taking it. CONCLUSIONS: A dose of 300 mg of aerosolized pentamidine given every four weeks was well tolerated and 60 to 70 percent effective in preventing a first episode of PCP in patients with HIV infection.

AIDS-Related Complex

Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1-infected patients with central nervous system involvement.

To assess the role of alpha-tumor necrosis factor in the pathogenesis of central nervous system involvement during human immunodeficiency virus type 1 infection, we recorded clinical data and measured alpha-tumor necrosis factor levels in serum and cerebrospinal fluid samples from 45 patients infected with human immunodeficiency virus type 1, classified as group II/III (10), group IV A (5), group IV B (10), and group IV C-1 (20) of the Centers for Disease Control acquired immunodeficiency syndrome classification system and 42 controls. Alpha-tumor necrosis factor was above the limit of detection in only 3 of 15 sera and 3 of 15 cerebrospinal fluid samples from patients in group II/III and group IV A, whereas it was detected in 17 of 30 sera (p less than 0.05) and 22 of 30 cerebrospinal fluid (p less than 0.0002) samples from clinically more advanced patients (group IV B and group IV C-1). Alpha-tumor necrosis factor mean values were 21.5 pg/ml in sera and 50.0 pg/ml in cerebrospinal fluid from group IV B patients and 30.4 pg/ml in sera and 24 pg/ml in cerebrospinal fluid from group IV C-1 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex