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Biomedical subjects

E Tamburrini

Publications and source records attributed to E Tamburrini.

At least 19 recordsLinked to original sources
PubMed2006

Diagnosis of HIV infection in pregnancy: data from a national cohort of pregnant women with HIV in Italy.

We analysed the characteristics of the pregnancies with a previously undetected HIV infection in a national observational study of pregnant women with HIV in Italy. In a total of 443 pregnancies with available date of HIV diagnosis, 118 were characterized by a previously undetected HIV infection (26.6%, 95% CI 22.5-30.8). The following factors were independently associated with this occurrence in a multivariate analysis (adjusted odds ratios; 95% CIs): foreign nationality (5.1, 2.8-9.3); no pre-conception counselling (35.9, 4.8-266.1); first pregnancy (2.1, 1.2-4.0); asymptomatic status (6.8, 1.5-30.6). Women with previously undetected infection started antiretroviral treatment significantly later during pregnancy (P < 0.001). Missed diagnosis was responsible for one case of transmission. A high rate of previously undetected HIV infection was observed. This suggests a good HIV detection during pregnancy, but also the need to reinforce HIV testing strategies among women of childbearing age. We identified some determinants which may be considered for intervention measures.

Adult↗
PubMed2006

Pharmacokinetics of nelfinavir in HIV-1-infected pregnant and nonpregnant women.

AIMS: To compare steady-state nelfinavir (NFV) pharmacokinetics in pregnant and nonpregnant HIV-infected women. METHODS: Twenty-five pregnant HIV-infected women were selected from an ongoing observational study evaluating the pharmacokinetics of antiretroviral agents during pregnancy. Twenty of them were in the third and five in the second trimester. Data for the control group of 21 HIV-infected nonpregnant women were taken from a previous multicentre pharmacokinetic trial. All the participating women achieved steady-state plasma concentrations while on a highly active antiretroviral therapy (HAART) regimen including NFV (1250 mg bid) and two nucleoside reverse transcriptase inhibitors (NRTIs). Blood samples for NFV measurement were collected predose (C(trough)) and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 12 h post dose. RESULTS: During the third trimester of pregnancy NFV AUC(0-12 h) median (range) values were 25.76 (12.61-42.74) microg h(-1) ml(-1), and were 32.49 (19.16-63.81) microg h(-1) ml(-1) in the control group [mean difference - 9.30 microg h(-1) ml(-1); 95% confidence interval (CI) -15.76, -2.83; P < 0.05). Median oral clearance (CL/F) was significantly higher in pregnant women than in the control group (48.5 l h(-1), range 29.3-99.1 l h(-1) vs. 38.5 l h(-1), range 19.6-65.2 l h(-1); mean difference 12.6 l h(-1); 95% CI 3.3, 21.9) but the difference disappeared when CL/F was adjusted for body weight. C(trough) was significantly (P < 0.01) lower in pregnant compared with nonpregnant women (median 0.8 microg ml(-1), range 0-2.6 microg ml(-1) vs. 1.5 microg ml(-1), range 0.5-4.9 microg ml(-1); mean difference -1.0 microg ml(-1); 95% CI -1.7, -0.31). The median elimination half-life of NFV observed during pregnancy was 3.7 h (range 1.4-6.6 h), compared with 5.2 (range 3.1-10.1 h) in the control group (mean difference -1.7; 95% CI -2.8, -0.51). CONCLUSIONS: Our results indicate that women in the later stages of pregnancy may be exposed to subtherapeutic concentrations of NFV. Thus, adjustments in drug dosage or frequency of administration may be required.

Female↗
PubMed2006

Aetiological factors related to a positive direct antiglobulin test result in human immunodeficiency virus-infected patients.

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the clinical importance and causes of a positive result in the direct antiglobulin test (DAT) in human immunodeficiency virus-infected (HIV(+)) patients. We therefore studied haematological parameters in outpatient samples, and also analysed the impact of highly active anti-retroviral therapy (HAART) on the DAT results. STUDY DESIGN AND METHODS: Haematological parameters, clinical stages, chemo-antibiotic treatments and HAART treatment were studied to determine any relationships with DAT results in 115 consecutive HIV(+) patients. RESULTS: Significantly lower haemoglobin (Hb) levels were detected in patients with HIV who had a positive DAT result. Hepatitis C virus (HCV) co-infection (odds ratio 2.529) and trimethoprim-suphamethoxazfole (TMP-SMX) prophylaxis (odds ratio 3.751) had a significant association with DAT positivity. Patients receiving HAART were less likely to have a positive DAT [odds ratio (OR) 0.383; P = 0.035]. Among the patients treated with TMP-SMX, those with a positive DAT had lower Hb levels (11.9 g/dl) than those with a negative DAT (14.2 g/dl; P = 0.04). HCV antibody positivity and TMP-SMX prophylaxis showed a cumulative effect on positive DATs (OR 4.533). The surface exploratory analysis indicated the distribution of the positive DATs in relationship with the CD4(+) count and Hb levels. CONCLUSIONS: Significantly lower Hb levels were detected in DAT-positive HIV(+) patients. HCV co-infection and TMP-SMX prophylaxis appear to confer an increased risk of DAT positivity. The presence of red blood cell autoantibodies may be associated with anaemia in HIV disease in the absence of overt haemolysis.

Anemia↗
PubMed2001

Mutations in dihydropteroate synthase gene of Pneumocystis carinii in HIV patients with Pneumocystis carinii pneumonia.

The purpose of this study was to determine whether dihydropteroate synthase gene (DHPS) mutations were associated with the failure of sulpha/sulphone drugs used as prophylaxis agents in HIV infected patients. Results suggested that DHPS mutations were significantly associated with failure of anti-Pneumocystis carinii sulphone prophylaxis (P=0.031). An increasing number of mutant P. carinii strains have been isolated from patients no longer having prophylaxis. There was no statistically significant difference in severity or outcome of the pneumonia caused by wild-type or mutant DHPS. Moreover, two of the three patients with mutant P. carinii pneumonia (PCP) were successfully treated with sulpha drugs. We think that P. carinii drug-resistance could be an emerging problem for immunocompromised patients including those with HIV infection.

Adult↗
PubMed1999

Pneumocystis carinii infection in young non-immunosuppressed rabbits. Kinetics of infection and of the primary specific immune response.

The aim of this study was to determine the kinetics, the dissemination of the infection and the immunological response to Pneumocystis carinii primary infection in a non-immunosuppressed rabbit model. For this purpose, we developed a nested PCR that amplified a portion of the mitochondrial large-subunit rRNA gene of rabbit-derived P. carinii. The PCR detected P. carinii DNA in lung and bronchoalveolar lavage fluids from 14- to 45-day-old rabbits but not in their serum. No P. carinii DNA was detected in extrapulmonary organs from 28-day-old rabbits with P. carinii pneumonia. ELISA and immunoblotting analysis showed that 5-day-old pups had elevated specific IgG. The IgG concentration sharply decreased, reaching a trough on day 21, and from then onwards progressively increased as the infection cleared. Conversely, the specific IgM concentration increased during the infection and peaked on day 28. IgG mainly recognized a 50-kDa subunit of P. carinii organisms; IgM recognized first a 45-kDa subunit on day 21, whereas from day 28 onwards it also recognized the 50-kDa subunit. A P. carinii-specific splenocyte proliferative response was observed on day 45. These findings suggest that P. carinii primary infection is a time-limited and a lung-limited event and contribute new information on the relationship between the kinetics of primary P. carinii infection and the immunological response in a model that mimics the primary infections in humans.

Aging↗
PubMed1998

Phase II controlled trial of post-exposure immunization with recombinant gp160 versus antiretroviral therapy in asymptomatic HIV-1-infected adults. VaxSyn Protocol Team.

OBJECTIVE: To alter the natural course of HIV-1 infection by inducing or potentiating immune responses to HIV-1 envelope glycoprotein. DESIGN: Multicentre, double-blind, three-arm, placebo-controlled study. SETTING: Outpatients attending clinics in two University Hospitals. PATIENTS: Ninety-nine asymptomatic HIV-1-infected adults with CD4+ T-cell counts > 400 and < 600 x 10(6)/l and no previous antiretroviral therapy were included. INTERVENTIONS: Patients were randomly assigned to three groups treated with: (i) gp160 in alum over a 2-year period in combination with placebo for the full study duration (n = 32); (ii) gp160 in alum over a 2-year period in combination with zidovudine for the full study duration (n = 34); and (iii) alum over a 2-year period in combination with zidovudine for the full study duration (n = 33). RESULTS: Immunotherapy was well tolerated and no significant differences in disease progression were seen in the treatment groups. The majority of patients (85%) receiving gp160 showed persistent lymphoproliferative responses to the immunogen and to a different Env antigen preparation. CD4+ cell count changes in patients receiving zidovudine alone were significantly higher than those seen in patients receiving immunotherapy alone after 1 year of treatment. Zidovudine administration was associated with initial transient reduction of plasma viraemia. CONCLUSIONS: Prolonged immunization with a soluble HIV-1 subunit provided no benefit to asymptomatic HIV-1-infected patients and was inferior to zidovudine monotherapy. Furthermore, immunization with gp160 shortened the duration of the transient viral load reduction induced by zidovudine.

AIDS Vaccines↗
PubMed1998

Potential impact of Pneumocystis genetic diversity on the molecular detection of the parasite in human host.

Our aim was to evaluate if genetic diversity of Pneumocystis carinii could influence the detection by molecular techniques in bronchoalveolar lavage (BAL) fluids and in non-invasive specimens (induced sputum, oropharyngeal washing and serum/blood). P. carinii is morphologically similar in different hosts although several strains have been identified by biomolecular techniques. Variations of mt-LSU and ITSs sequences could determine a lack of hybridization of some clinical samples and could have diagnostic consequences with loss in sensitivity and specificity of available molecular tests, but at the moment no data support a significant impact of genetic diversity in these sequences on molecular detection of P. carinii for clinical purposes.

DNA Primers↗
PubMed1998

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↗
PubMed1998

Genetics, metabolism and host specificity of Pneumocystis carinii.

Pneumocystis carinii is a major cause of severe pneumonia in immunosuppressed individuals, especially in those with human immunodeficiency virus (HIV) infection during their period of progression to acquired immunodeficiency syndrome (AIDS), and constitutes a worldwide problem to public health. Recently, significant advances in the development of experimental animal models of P. carinii infection, as well as in our knowledge of the genetic diversity and taxonomy of P. carinii, have been made. These advances may contribute to our understanding of the transmission of P. carinii pneumonia (PCP) and to the development of new prevention and control strategies. This paper addresses questions relating to the epidemiology of PCP including the detection of the parasite in the environment and in patients, the mechanism of genetic variation of the major surface glycoprotein (MSG) of P. carinii, and host-related genetic variation among isolates of this organism, emphasizing phenotypic expression and its impact on epidemiology and taxonomy.

AIDS-Related Opportunistic Infections↗
PubMed1997

Biodiversity of Pneumocystis carinii hominis: typing with different DNA regions.

The purpose of this study was to identify the most useful gene for the detection of biodiversity of Pneumocystis carinii hominis isolates and to compare samples from French and Italian subjects. We studied 20 bronchoalveolar lavage fluid specimens from 20 human immunodeficiency virus-infected patients (10 French and 10 Italian patients) with Pneumocystis carinii pneumonia by DNA sequencing of the thymidylate synthase (TS), 5S rRNA, large-subunit mitochondrial rRNA (mt LSU rRNA), and internal transcribed spacer (ITS1 and ITS2) genes. Thirteen of the 20 sequenced samples had the prototype TS gene sequence. Fourteen of the 20 samples showed the prototype sequence of the 5S rRNA gene, and 6 had variant sequences of the 5S rRNA gene. The mt LSU rRNA gene was sequenced for 18 of the 20 samples; all sequences were different from the prototype sequence and were classified into four groups. Thirteen of the 20 ITS1 and ITS2 sequences were analyzed, and all the sequences were found to be different from the prototype sequence and were classified into 10 groups. The internal transcribed spacer regions thus appear to be the most discriminatory region of DNA for analysis of the biodiversity of P. carinii hominis isolates.

AIDS-Related Opportunistic Infections↗
PubMed1997

Detection of Pneumocystis carinii in respiratory specimens by PCR-solution hybridization enzyme-linked immunoassay.

By using a recently developed PCR-solution hybridization enzyme-linked assay (PCR-SHELA), we investigated Pneumocystis carinii in bronchoalveolar lavage fluid samples and induced sputa of patients with pneumocystosis. In detecting P. carinii, PCR-SHELA proved more sensitive than immunofluorescence staining or a single PCR and significantly more diagnostically specific than a nested PCR. Our data suggest that PCR-SHELA could be used to detect P. carinii organisms in respiratory samples, particularly in patients with uncertain diagnoses.

AIDS-Related Opportunistic Infections↗
PubMed1996

Non specific PCR products using rat-derived Pneumocystis carinii dihydrofolate reductase gene-specific primers in DNA amplification of human respiratory samples.

DNA amplification using dihydrofolate reductase (DHFR) primers in bronchoalveolar lavage fluids (BALFs) from patients with Pneumocystis carinii (PC) pneumonia yielded low sensitivity and specificity. Amplified products of BALFs from an AIDS patient without PC pneumonia and five patients with PC pneumonia were cloned and sequenced. All samples showed the same sequence without any homology with DHFR cDNA of rat PC, or with any DHFR sequences in databases at the DNA or amino acid level. The data demonstrate that these DHFR primers amplify a non-specific region of DNA with a sequence unrelated to the human PC DHFR gene both in PC positive and in PC negative samples. This finding precludes the use of these DHFR primers for the diagnosis of PC pneumonia in respiratory specimens.

Base Sequence↗
PubMed1996

Imbalance between Pneumocystis carinii cysts and trophozoites in bronchoalveolar lavage fluid from patients with pneumocystosis receiving prophylaxis.

Detection and quantification of different Pneumocystis carinii (PC) life cycle forms were performed by polymerase chain reaction (PCR) and by morphological stains on bronchoalveolar lavage fluids (BALF) from HIV-infected patients with P. carinii pneumonia (PCP). The number of PC trophozoites was higher in patients with PCP who were receiving prophylaxis than in those not receiving prophylaxis. Also the cyst: trophozoite ratio was lower in the first group. No difference was observed between patients receiving different prophylactic medications. The imbalance between PC forms in BALF from patients with PCP receiving anti-PC prophylaxis may hamper the sensitivity of cyst stains. Multiple stains or PCR examination should be performed on BALF from patients with clinically suspected PCP who are receiving prophylaxis.

AIDS-Related Opportunistic Infections↗