Biomedical subjects

Fulvio Adorni

Publications and source records attributed to Fulvio Adorni.

14 recordsLinked to original sources

PubMed2006

Vocal improvement after voice therapy in unilateral vocal fold paralysis.

Unilateral vocal fold paralysis (UVFP) is associated with changes in acoustic and aerodynamic voice measurements and can have a significant impact on a patient's quality of life. Few objective data regarding the efficacy of voice therapy for UVFP exist. The aim of this study was to retrospectively analyze voice modifications in a group of patients with UVFP before and after voice therapy. Forty patients with UVFP of different etiology were included in the study. Each subject had voice therapy with an experienced speech/language pathologist twice a week; the mean number of sessions was 12.6. A multidimensional assessment protocol was used; it included videoendoscopy, the maximum phonation time (MPT), the GIRBAS scale, spectrograms and a perturbation analysis, and the Voice Handicap Index (VHI). Pre- and posttreatment data were compared by means of the Wilcoxon and Student's t tests. A complete glottal closure was seen in 8 patients before voice therapy and in 14 afterward. Mean MPT increased significantly. In the perceptual assessment, the difference was significant for five out of six parameters. A significant improvement was found on spectrographic analysis; as for perturbation analysis, the differences in jitter, shimmer, and noise-to-harmonic ratio values were significant. VHI values showed a clear and significant improvement. A significant improvement of voice quality and quality of life after voice therapy is an often reached and reasonable goal in patients with UVFP.

Adolescent↗

PubMed2006

Subclinical hypothyroidism in HIV-infected subjects.

OBJECTIVES: The correlation between subclinical hypothyroidism [thyroid stimulating hormone (TSH)>4 mIU/L with normal free triiodothyroxine and free thyroxine levels], HIV infection and HAART is still unclear. PATIENTS AND METHODS: To evaluate the predictive factors of subclinical hypothyroidism in an HIV-infected population, we identified three groups of subjects: G1, subjects on stable highly active antiretroviral therapy (HAART) (for at least 1 year) at baseline and at month 24 (n=97); G2, subjects naive at both baseline and month 24 (n=47); G3, subjects starting HAART at baseline (n=46). RESULTS: The three groups were comparable with respect to age, gender, body weight and prevalence of HCV infection. At baseline, subclinical hypothyroidism was detected in 14 subjects in G1 (14.4%), 5 in G2 (10.6%) and 4 in G3 (8.7%) (P=0.18) and these were excluded from the analysis. At month 24, 15 subjects had developed subclinical hypothyroidism: 4 in G1 (4.8%), 3 in G2 (7.1%) and 8 in G3 (19.0%). In the multivariable analysis, the higher increase in total cholesterol was predictive of subclinical hypothyroidism (RR: 1.53 for each additional 10 mg/dL, 95% CI 1.23-1.90; P<0.01); other variables, which were statistically significant in the univariate analysis, such as G3 group, body weight and higher increase in CD4+ cell count and in triglyceride serum levels were not confirmed to be associated with TSH alterations. CONCLUSIONS: The occurrence of subclinical hypothyroidism in HIV-positive patients seems to be related to the increase in total cholesterol serum levels occurring after HAART initiation. Thyroid function should be monitored in all HIV-infected subjects, especially in those starting HAART.

Adult↗

PubMed2006

Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients.

BACKGROUND: Vpr (viral protein R) is a 96 amino acids soluble protein that is expressed late during viral replication. Recent studies have focused on the role of a mutation at position 77 that might be associated with the condition of long-term non-progression, but data are still controversial. PATIENTS AND METHODS: Fifteen long-term non-progressors (LTNP), 19 therapy-naive HIV-1-infected patients with progressive disease (Pr), 23 HIV-1-infected patients receiving sub-optimal therapy with dual nucleoside [nucleoside reverse transcriptase inhibitor (NRTI)] therapy but efficiently controlling viral replication (STP) and 19 antiretroviral therapy multi-experienced patients with actively replicating virus (MEP) were analysed. HIV-RNA was extracted from plasma samples, the Vpr region was amplified, cloned and sequenced. The Pol gene was amplified, directly sequenced and analysed using Sequence Navigator software. RESULTS: A significantly higher prevalence of the R77Q mutation was evidenced both in LTNP (86.7%) and STP (73.9%) in comparison with Pr (42.1%) and MEP (42.1%), (P = 0.007). Comparing groups of patients with progressive disease (Pr + MEP) and groups with non-progressive disease (LTNP + STP) the probability of harbouring the R77Q mutation was significantly higher in non-progressors (odds ratio, 5.16; P = 0.001). CONCLUSIONS: Our results support the hypothesis of the association of R77Q mutation in the Vpr gene with delayed progression of HIV-1 disease. R77Q does not seem to be linked to a particular viral strain but might be associated to immunologic selection. The R77Q mutation might reduce CD4+ T-cell depletion possibly affecting T-cell survival in vivo by altering the pro-apoptotic activity of Vpr.

Adult↗

PubMed2006

A novel polymorphism in SEL1L confers susceptibility to Alzheimer's disease.

Alzheimer's disease (AD) is considered to be a conformational disease arising from the accumulation of misfolded and unfolded proteins in the endoplasmic reticulum (ER). SEL1L is a component of the ER stress degradation system, which serves to remove unfolded proteins by retrograde degradation using the ubiquitin-proteosome system. In order to identify genetic variations possibly involved in the disease, we analysed the entire SEL1L gene sequence in Italian sporadic AD patients. Here we report on the identification of a new polymorphism within the SEL1L intron 3 (IVS3-88 A>G), which contains potential binding sites for transcription factors involved in ER-induced stress. Our statistical analysis shows a possible role of the novel polymorphism as independent susceptibility factor of Alzheimer's dementia.

Aged↗

PubMed2006

Predictive factors of hyperlipidemia in HIV-infected subjects receiving lopinavir/ritonavir.

We studied 382 multiexperienced HIV-infected patients followed up for > or =3 months after starting lopinavir/ritonavir (LPV/r) to identify the factors predicting hypertriglyceridemia and high non-HDL cholesterol levels (triglycerides > or =200 mg/dl and/or non-HDL cholesterol > or =190 mg/dl) after 6 and 12 months of LPV/r exposure. The predictors of hypertriglyceridemia were higher baseline triglyceride levels [OR: 2.28 (95% CI: 1.67-3.12) for each additional 100 mg/dl; p = 0.001], the total duration of antiretroviral treatment [OR: 1.26 (95% CI: 1.12-1.41) for each additional year; p = 0.01], CDC stage C (OR: 2.06; 95% CI: 1.24-3.88; p = 0.02), and male gender (OR: 2.52; 95% CI: 1.42-4.74; p = 0.02); intravenous drug abusers seem less likely to develop the event (OR: 0.52; 95% CI: 0.37-0.92; p = 0.03). The predictors of high non-HDL cholesterol levels were higher baseline levels [OR: 3.92 (95% CI: 1.92-6.24) for each additional 100 mg/dl; p = 0.001) and the combination of NRTIs and NNRTIs with LPV/r (OR: 1.83; 95% CI: 1.10-3.69; p = 0.03). The 75 patients stopping LPV/r showed a significant reduction in median triglyceride and non-HDL cholesterol levels after 3 months of 39 mg/dl and 20 mg/dl (p = 0.01 for both), respectively. Patients with high triglyceride and non- HDL cholesterol levels at the start of LPV/r treatment are at higher risk of developing hyperlipidemia.

Adult↗

PubMed2005

Increased CD36 expression on circulating monocytes during HIV infection.

BACKGROUND: Metabolic alterations and abnormalities of fat distribution are common findings in antiretroviral-treated HIV-1-infected patients. CD36 is a multifunctional receptor with a wide tissue distribution that plays a crucial role in the cellular uptake and metabolism of lipids. OBJECTIVES: To define the level of CD36 expression on circulating monocytes from HIV-1-infected patients and healthy controls (HCs) and to correlate CD36 expression levels with metabolic and immunovirologic parameters. METHODS: CD36 expression on peripheral blood monocytes was measured by means of flow cytometry in 165 HIV-1-infected patients and in 35 HCs. Statistical analysis was performed by means of univariate and multivariate analysis of variance models. RESULTS: CD36 expression was significantly higher in HIV-1-infected patients compared with HCs (P < 0.0001). HIV-1 infection was the only variable associated with CD36 expression on multivariate analysis, whereas no correlation was found between CD36 level and age, sex, body mass index, lipid serum levels, HIV RNA levels, time on antiretroviral therapy, or kind of antiretroviral regimen. CONCLUSIONS: HIV-1 infection is associated with increased expression of CD36 on circulating monocytes, and antiretroviral drugs play only a minor role in the complex homeostasis of this receptor. Given its role in the cellular uptake and accumulation of lipids, CD36 increased levels on monocytes could represent a proatherogenic condition in HIV-infected patients.

Adult↗

PubMed2004

[13C]Methionine breath test: a novel method to detect antiretroviral drug-related mitochondrial toxicity.

OBJECTIVES: A major side effect of antiretroviral drugs is nucleoside reverse transcriptase inhibitor (NRTI)-related mitochondrial toxicity, the in vivo diagnosis of which is difficult and not yet standardized. We used the [(13)C]methionine breath test to investigate hepatic mitochondrial oxidation in HIV-1-infected patients receiving antiretroviral therapy. PATIENTS AND METHODS: The [(13)C]methionine breath test was performed in healthy subjects (n=10), HIV-infected patients on antiretroviral therapy with (n=6) and without (n=15) hyperlactataemia and naive HIV-infected patients (n=11). After oral administration of [(13)C]methionine (2 mg/kg body weight), hepatic methionine metabolism was measured by breath (13)CO(2) enrichment, expressed as delta over baseline (DOB) every 15 min for 120 min by mass spectrometry. RESULTS: The four study groups showed a significant difference in (13)CO(2) exhalation (P=0.001). HIV-infected patients on antiretroviral therapy with normal serum lactate had reduced exhalation of (13)CO(2) compared with healthy subjects (DOB mean peak: 8.82+/-0.62 versus 11+/-0.9, P<0.05). HIV patients with hyperlactataemia had even lower values when compared with patients with normal lactataemia (DOB mean peak: 4.98+/-0.68 versus 8.82+/-0.62, P<0.05). CONCLUSIONS: The [(13)C]methionine breath test possibly showed mitochondrial impairment in antiretroviral-treated HIV-positive patients, particularly with hyperlactataemia. This non-invasive test can be used to monitor drug-related mitochondrial toxicity in vivo and to discover early and asymptomatic damage of the respiratory chain.

Adult↗

PubMed2004

Lopinavir/ritonavir vs. indinavir/ritonavir in antiretroviral naive HIV-infected patients: immunovirological outcome and side effects.

We compared immunovirological outcomes and toxicities of HAART regimens including LPV/r and IDV/r in antiretroviral naïve HIV-1 patients. We retrospectively selected 55 patients starting LPV/r and 52 starting IDV/r as first-line HAART. Immunovirological and metabolic parameters were recorded at baseline and every 3 months as were side effects, AIDS-defining events and deaths. Demographic characteristics and NRTIs included in the regimens were comparable. Both groups reached undetectable HIV-RNA plasma viremia from third month and maintained during follow-up. However, patients receiving IDV/r had a lower probability to obtain virological success (RH: 0.46). Patients receiving IDV/r patients showed a greater increase of total cholesterol (P = 0.01). Three patients on LPV/r and 21 on IDV/r discontinued the drug for toxicity, leading to a 8.40 higher risk of discontinuation in the latter group. In our clinical setting IDV/r showed to be less effective and more toxic than LPV/RTV as first-line HAART.

Adult↗

PubMed2003

Simplification of protease inhibitor-containing regimens with efavirenz, nevirapine or abacavir: safety and efficacy outcomes.

OBJECTIVE: To describe the immunological and virological outcome, and the factors associated to discontinuation in patients switching to a regimen containing efavirenz (EFV), nevirapine (NVP) or abacavir (ABC) after long-term viral suppression under protease inhibitor-including HAART. DESIGN: Observational study at three outpatient clinics for HIV care in Italy. METHODS: Patients with HIV RNA <80 copies/ml and CD4 >200 cells/ml for at least 6 months on a protease inhibitor-containing treatment who switched to NVP, EFV or ABC were included in the study. End-points were immunological failure, virological failure and discontinuation due to toxicity. Survival analyses were performed to find out any independent variables predictive of reaching the end-points. RESULTS: 177 patients were enrolled; 85 started EFV, 54 NVP and 38 ABC as part of the simplification regimen. 16/159 patients experienced immunological failure: the variables associated to CD4 count decrease were HIV RNA set point value (HR 2.32 for each log10 copies more, P=0.040) and intolerance/toxicity as reason for simplification (HR 3.96, P=0.05). 13/151 subjects showed virological failure; an AIDS diagnosis (HR 6.04, P=0.021) and the use of NVP (HR 7.98, P=0.027) were associated to a worse virological outcome, while patients naive before HAART showed a lower risk of failure (HR 0.008, P=0.007). 16/177 patients discontinued simplification regimen due to toxicity; longer HAART duration before switch was associated to risk reduction (HR 0.92, P=0.004). CONCLUSIONS: Simplification is safe and effective, but it should be offered to patients with shorter treatment duration, and in good clinical and immunovirological conditions.

Alkynes↗

PubMed2003

Virological success of lopinavir/ritonavir salvage regimen is affected by an increasing number of lopinavir/ritonavir-related mutations.

We evaluated the virological outcome of lopinavir/ritonavir (LPV/RTV) in 224 HIV-1-infected and protease inhibitor (PI)-experienced patients showing virological failure to a highly active antiretroviral therapy (HAART) regimen and followed up for at least 3 months. At baseline, the median level of plasma viraemia was 4.61 log10 copies/ml (range 3-6.48) and the median CD4 cell count was 219 cells/mm3 (range 1-836). During a median follow-up of 272 days (range 92-635), we observed an increase in the number of CD4 cells (P=0.02) and a dramatic decrease in plasma viraemia levels (P=0.0001), which became undetectable in 122 patients (54.5%). The closely related predictive factors were baseline plasma viraemia levels and the number of mutations known to reduce susceptibility to LPV/RTV. Thirty-one patients (13.8%) discontinued LPV/RTV during the follow-up, and one AIDS event and three deaths were recorded. Of the 134 patients (59.8%) who underwent a baseline genotype resistance test, 22 (16.4%) had > or = 6 mutations known to reduce LPV/RTV susceptibility; plasma viraemia became undetectable in 76 patients (56.7%), only five of whom harboured > or = 6 mutations at baseline (P=0.0001). The independent predictive factors related to virological success were plasma viraemia levels and the number of mutations reducing susceptibility to LPV/RTV at baseline; each additional log10 copies/ml of HIV RNA reduced the probability of virological success by 34.0% and each extra mutation by 14.5%.

Adult↗

PubMed2003

Correlates of risk of adipose tissue alterations and their modifications over time in HIV-1-infected women treated with antiretroviral therapy.

OBJECTIVE: To assess the correlates of risk of the different types of lipodystrophy and their modifications over time in a cohort of HIV-positive women receiving antiretroviral therapy (ART). METHODS: A consecutive series of HIV-infected women receiving ART was prospectively enrolled between 1 and 31 March 1998, and followed up for 2 years. Adipose tissue alterations (ATAs) and their variations over time were assessed by means of clinical observation and anthropometric measurements, and logistic regression analysis was used to describe the associated risk factors identified by univariate and multivariate analyses. RESULTS: One-hundred-and-seventeen of the 212 women (55.2%) developed ATAs during the 24 months of follow-up. Central adiposity was observed in 95 patients and peripheral lipoatrophy in 91, with 21 patients (9.9%) showing pure lipoatrophy, 26 (12.3%) pure fat accumulation and 70 (33%) combined forms. Only six of the 223 regional adipose tissue alterations identified in 74 patients during the first 12 months of the study had disappeared by month 24. Of the 43 patients who developed breast enlargement during the first 12 months, 11 (25.6%) showed a decrease in breast size during the second year of follow-up that was unrelated to changes in therapy or therapeutic success. The development of ATAs during the first 12 months of follow-up independently correlated with protease inhibitor (PI) use (OR 2.81, P=0.002) but, by the end of the second year of follow-up, the only factor significantly related to the development of ATAs was the overall duration of ART (OR 1.85, P=0.041). The use of PI significantly increased the risk of developing central adiposity during the first 12 months of the study (OR 2.27, P=0.002), whereas the only variable significantly influencing the risk at month 24 was HIV-infection due to intravenous drug use, which proved to be protective (OR 0.53, P=0.043). During the first 12 months of follow-up, the development of peripheral lipoatrophy was significantly associated with stavudine (OR 2.19, P=0.037) and PI use at enrolment (OR 2.27, P=0.023). At the end of the study, the variables associated with peripheral lipoatrophy were stavudine use at enrolment (OR 2.82, P=0.002), ART exposure for >1000 days at enrolment (OR 2.32, P=0.007), a CD4 cell count of >200/microl at enrolment (OR 2.89, P=0.002) and an age of >28 years (OR 1.91, P=0.036). The only factor significantly associated with an increased risk of breast enlargement during the first 12 months of follow-up was PI use (adjusted OR 2.51; 95% CI: 1.16-5.46, P=0.02); however, at month 24, none of the tested variables was associated with a significantly increased risk of this ATA. CONCLUSIONS: ATAs (particularly central adiposity) are frequent in women treated with ART, and the different forms have different correlates of risk. Once they have become clinically evident, they generally tend to remain or worsen, and improve in only a small minority of cases. The considerable variations in adipomasty over time are apparently unrelated to changes in ART.

Adipose Tissue↗

PubMed2002

Thrombotic microangiopathy in patients with acquired immunodeficiency syndrome before and during the era of introduction of highly active antiretroviral therapy.

The incidence of thrombotic microangiopathy (TMA) was retrospectively evaluated in a cohort of 1223 patients with acquired immunodeficiency syndrome (AIDS) who were observed from January 1985 through December 1996 (before the era of highly active antiretroviral therapy [HAART]), and the incidence was prospectively assessed for 347 patients with AIDS during the period of January 1997 through December 2000 (during the HAART era). Seventeen cases were reported in the former cohort (1.4%). The increased risk of developing TMA was statistically significant in patients with cryptosporidiosis or AIDS-related cancer but not in those with other diseases. In the 1997-2000 cohort, no cases were observed during follow-up. TMA is associated with conditions observed in the advanced phases of human immunodeficiency virus infection. The disappearance of TMA during the HAART era may be explained by the lower percentage of patients with long-lasting CD4+ T cell depletion, advanced AIDS, or cryptosporidiosis or who have undergone multiple courses of chemotherapy for treatment of cancer.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Increased risk of developing peripheral neuropathy in patients coinfected with HIV-1 and HTLV-2.

One thousand one hundred fifty-two HIV-1-positive patients were screened for HTLV-2 infection, and the AIDS-free coinfected individuals were consecutively included in a longitudinal study with the aim of investigating the role of HTLV-2 in the progression to AIDS and the development of specific neurologic diseases. Two matched HIV-1-positive/HTLV-2-negative controls for each coinfected individual were also enrolled in the study. HTLV-2 infection was found in 95 (8.2%) of the HIV-1-positive patients, 30 of whom were followed up for a median of 28.5 months. No significant differences were observed between them and the patients infected with HIV-1 alone in terms of the rate of decline in CD4 cell counts, progression to AIDS, or AIDS mortality, but they had an increased risk of developing peripheral neuropathy (hazard ratio, 3.3; 95% confidence interval, 1.3-8.0; p =.009). One coinfected patient developed myelopathy during the follow-up. In the second part of the study, aimed at preliminarily assessing the effect of highly active antiretroviral therapy (HAART) on the incidence of peripheral neuropathy, we extended our observations to two groups of coinfected and singly infected individuals receiving HAART. An 80% decrease in incidence of peripheral neuropathy was observed among both groups without any significant difference between them. These results support the hypothesis that HTLV-2 plays a role in the development of neurologic abnormalities in HIV-1-infected patients and suggest that the immune reconstitution due to HAART may limit the activity of HTLV-2 as an opportunistic agent.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Body habitus changes and metabolic alterations in protease inhibitor-naive HIV-1-infected patients treated with two nucleoside reverse transcriptase inhibitors.

BACKGROUND: Cross-sectional and retrospective surveys suggest that nucleoside reverse transcriptase inhibitors (NRTIs) contribute to the metabolic and morphologic alterations observed in patients on antiretroviral therapy (ART). OBJECTIVES: To assess the risk of developing body habitus changes (BHCs) and metabolic abnormalities in protease inhibitor (PI)-naive HIV-1-infected patients treated with two NRTIs, and the risk associated with each of these drugs. DESIGN: Prospective cohort study. PATIENTS AND METHODS: The BHCs occurring in 335 patients treated with two NRTIs were evaluated every 3 months. The laboratory tests included determination of CD4 cell counts and the measurement of HIV RNA, serum glucose, cholesterol, and triglyceride levels. Cox proportional hazard models were used to describe the factors associated with the development of BHCs. RESULTS: During a median exposure of 747.5 days, 46 patients (13.7%) developed BHCs: nine fat accumulation alone, 12 fat loss alone, and 25 combined fat loss and accumulation in different body regions. Fat loss alone occurred after a significantly longer median duration of treatment than the other two forms (p =.004). The risk of developing any BHC was significantly higher in female patients (p <.0001). Fat loss was the prevalent alteration in males. Hypertriglyceridemia was observed in 76 patients (22.7%), hypercholesterolemia in 35 (10.5%), and hyperglycemia in 48 (14.3%). The adjusted risk of developing hypertriglyceridemia was higher in the stavudine-treated patients (p =.04) and in those who had previously received ART (p =.02). The only independent factor associated with the development of hypercholesterolemia was to be ART experienced at baseline (p =.02), whereas age was associated with the development of hyperglycemia (p =.0096). CONCLUSIONS: Treatment with NRTIs may be responsible for the same morphologic alterations as those observed in patients treated with PIs. Moreover, altered triglyceride levels are also frequently observed. The different timing of presentation and gender distribution of BHCs suggest that multiple pathogenetic mechanisms are involved.

Adult↗