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Biomedical subjects

M Galli

Publications and source records attributed to M Galli.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cardiovascular disease risk factors in HIV-infected patients in the HAART era.

HIV infection is accompanied by disturbances in lipid and glucose metabolism, which are further compounded by changes induced by antiretroviral drugs. There is increasing concern that these changes will lead to an epidemic of cardiovascular disease. Cardiovascular disease will no doubt increase, but current data indicate that the average absolute levels are likely to remain low, although patients with additional risks (smoking, hypertension, diabetes, age, family history, etc.) are certainly more susceptible. The complications of therapy need to be taken into account when deciding on the time of treatment, and reducing risk factors should become a routine aspect of the care of an HIV population that now lives longer as a result of highly active antiretroviral therapy.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Role of PCR in diagnosis and prognosis of visceral leishmaniasis in patients coinfected with human immunodeficiency virus type 1.

A group of 76 consecutive human immunodeficiency virus (HIV)-positive patients with fever of unknown origin (n = 52) or fever associated with pulmonary diseases was evaluated in order to assess the usefulness of PCR with peripheral blood in the diagnosis and follow-up of visceral leishmaniasis. We identified 10 cases of visceral leishmaniasis among the 52 patients with fever of unknown origin. At the time of diagnosis, all were parasitemic by PCR with peripheral blood. During follow-up, a progressive decline in parasitemia was observed under therapy, and all patients became PCR negative after a median of 5 weeks (range, 6 to 21 weeks). However, in eight of nine patients monitored for a median period of 88 weeks (range, 33 to 110 weeks), visceral leishmaniasis relapsed, with positive results by PCR with peripheral blood reappearing 1 to 2 weeks before the clinical onset of disease. Eight Leishmania infantum and two Leishmania donovani infections were identified by PCR-restriction fragment length polymorphism analysis. PCR with peripheral blood is a reliable method for diagnosis of visceral leishmaniasis in HIV-infected patients. During follow-up, it substantially reduces the need for traditional invasive tests to assess parasitological response, while a positive PCR result is predictive of clinical relapse.

Adult↗
PubMed2001

In vitro evolution of the human immunodeficiency virus type 1 gag-protease region and maintenance of reverse transcriptase resistance following prolonged drug exposure.

We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. Previous 3TC resistance did not impair the development of additional mutations in the protease and Gag-protease cleavage regions.

Drug Resistance, Microbial↗
PubMed2001

Molecular epidemiology of TT virus in Italy and phylogenesis of viral isolates from subjects at different risk for parenteral exposure.

The prevalence and genotype distribution of human TT virus (TTV) in Italy were analysed in 593 subjects at different risk of parenteral infection who included blood donors, patients with chronic type C hepatitis (HCV), thalassemic patients, patients on haemodialysis, human immunodeficiency virus type 1 (HIV-1)-negative intravenous drug users (IVDUs), and HIV-1-infected subjects (IVDUs, heterosexual contacts and homosexual males). Plasma TTV-DNA was detected using nested PCR with primers deduced from the N22 region of the open reading frame 1 (ORF-1) and from the untranslated region (UTR) of the viral genome. Phylogenetic analysis of the sequences obtained from ORF-1 was also undertaken. A high prevalence of plasma TTV-DNA was observed using the UTR primers, with rates varying from 83-100% in the study groups. Using the N22 primers, HIV-1 positive IVDUs and homosexual males, haemodialysed patients and thalassemic patients had a significantly higher TTV prevalence (range: 23.0-86.1%) than blood donors, who displayed a high frequency of positivity (10.6%). Sequence analysis of 127 N22-positive isolates revealed that 42.5% were of type 1, 53.5% of type 2, 2.4% of type 3, and that two isolates (1.6%) were closely related to genotypes 1-2 but distinct from the other major genotypes. TTV-2 was significantly more prevalent in patients at high risk for parenteral infection and in HIV-1 positive homosexuals. In sequential samples from 15 TTV-infected subjects, N22 sequences were detectable persistently in 12 (80.0%) and UTR sequences persisted in all 15 patients over a mean period of 29.6 months. This data indicates that TTV is widespread in Italy in parenterally exposed subjects, and that the infection frequently persists.

Adult↗
PubMed2001

Hypothesis and development of a minimally invasive approach for percutaneous transmyocardial revascularization with holmium laser.

BACKGROUND: Percutaneous transluminal myocardial revascularization (PTMR) is a new procedure to improve perfusion of the ventricular wall for patients with intractable angina and untreatable by surgery or conventional catheter-based intervention. Actually PTMR requires femoral approach to utilize 8F-9F system device. We now report the feasibility study of PTMR using a laser delivered through a novel Eclipse system and new 6F and 7F guiding catheters that allow to perform PTMR even in patients with peripheral vascular disease and particularly suitable for alternative small vascular access. METHODS: Percutaneous vascular access for PTMR treatment was obtained via the femoral or radial artery. A 6F or 7F mono-directional catheter carrying flexible fiber optics was used with a Holmium laser (Eclipse system) and was placed across the aortic valve into the left ventricular cavity to create channels of 5 mm in depth from the endocardial surface into the myocardial tissue. From June 1999 to September 2000, 39 patients (28 males, 11 females, mean age 72 +/- 8 years, range 58-86 years) underwent PTMR with the Eclipse system. Preoperative mean Canadian Cardiovascular Society (CCS) angina class was 3.5 +/- 0.5 and previous myocardial procedures had been performed in 39 patients (18 coronary artery bypass graft and 31 coronary angioplasty). RESULTS: The procedure was well tolerated and a procedural success was obtained in all patients (100%). We performed a mean of 19 +/- 7 channels in a mean fluoroscopy time of 21 +/- 9 min. We report only one procedural complication: one embolic stroke (2.4%). No hospital major adverse cardiac events were observed. The average length of hospital stay was 3.1 days. The mean CCS angina class at entry was 3.5 and it declined from 3.5 +/- 0.5 to 1.25 +/- 0.8 at discharge. At the follow-up of 8.2 +/- 3.9 months the mean CCS was 1.5 +/- 0.7. CONCLUSIONS: This experience confirmed the safety and technical feasibility of PTMR with this mini-invasive approach with a reduction in operative and fluoroscopy time. The PTMR with the 6F or 7F guiding catheter is feasible in high risk patients even when the femoral approach is contraindicated. Immediate and short-term results confirm that a clinical improvement is obtained in most patients.

Aged↗
PubMed2001

Virological response in multidrug-experienced HIV-1-infected subjects failing highly active combination regimens after shifting from lamivudine to didanosine.

The aim of this study (the RESCUE trial) was to verify the effect of a shift from a lamivudine-containing to a didanosine-containing regimen on viral replication in HIV-1-infected subjects who had experienced prior treatment failure. Sixteen patients (didanosine-experienced in 14/16 cases) were consecutively enrolled: eight patients shifted from lamivudine to didanosine without other changes in their drug regimen. The other eight shifted from lamivudine to didanosine and changed one or more of their other drugs according to their physician's judgement. At the time of the regimen shift, all the subjects exhibited a high-level phenotypic resistance to both zidovudine and lamivudine with changes at codons 70-219 in 100% of cases, at codon 215 in 13 of 16 patients, and the M184V substitution in 13/16 patients. Phenotypic susceptibility to didanosine was maintained in the majority of cases (14/16) despite the high prevalence of changes at codon 184. A statistically significant decrease in viral load (P<0.005) without a significant increase in CD4 lymphocytes (P=0.514) was observed after 3 and 6 months from the introduction of the didanosine-containing regimen. These findings suggest the possibility of achieving a viral load response to didanosine-containing regimens in patients with reverse transcriptase (RT) M184V mutations who were previously treated with this drug and its possible use in salvage combinations.

Acquired Immunodeficiency Syndrome↗
PubMed2001

[Acute myocardial infarction during labor: report of a case and review of the literature].

Acute myocardial infarction in pregnancy is a rare condition with substantial risk of maternal and fetal death. There is very little information about the use in this setting of percutaneous coronary interventional therapy. Together with literature review on this topic, we present the case of a 33-year-old 39-week pregnant woman who sustained during labor an acute transmural anterior myocardial infarction. Immediately after successful cesarean section, she was treated by primary percutaneous coronary angioplasty and direct stenting of the left anterior descending coronary artery with maternal and fetal excellent outcome.

Adult↗
PubMed2000

Independent and incremental prognostic value of (201)Tl lung uptake at rest in patients with severe postischemic left ventricular dysfunction.

BACKGROUND: An elevated (201)Tl lung uptake after stress is related to an adverse prognosis. METHODS AND RESULTS: The functional and prognostic significance of resting (201)Tl lung uptake was assessed in 124 consecutive patients with ischemic heart disease and ejection fraction </=35% undergoing rest-redistribution tomography to evaluate myocardial viability. (201)Tl lung uptake significantly correlated with pulmonary wedge pressure (r=0.66; P:<0.01) and with a restrictive physiology by Doppler echocardiography (P:<0.001). During a 13+/-13-month follow-up, 13 patients died and 23 patients required hospitalization as the result of worsening heart failure or nonfatal myocardial infarction (cumulative events rate 29%). Patients with events had a significantly higher (201)Tl lung/heart ratio (L/H) (P:<0.001). A L/H value >0.61 best separated patients with and without events (ROC area under curve 0.82). Event-free survival was significantly lower in patients with L/H >0.61 (P:<0. 001); L/H >0.61 (chi(2)=10.8; P:<0.001) and a restrictive filling pattern (chi(2)=3.6; P:<0.05) were independent predictors of events. The prognostic value of L/H was incremental over that obtained by clinical, echographic and Doppler data (global chi(2)=20.8). CONCLUSIONS: In patients with severe postischemic left ventricular dysfunction undergoing rest-redistribution (201)Tl imaging, an increased lung tracer uptake showed incremental prognostic value over clinical and other imaging findings, providing clinically useful risk assessment.

Adult↗
PubMed2000

Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure.

We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 variants in 177 patients who failed to respond to combination therapy. Patients had received protease inhibitors (PI) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs) after a long-term experience with nucleoside reverse transcriptase inhibitors (NRTIs) (including zidovudine monotherapy). Two of 177 patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had the 69 6-bp insert. Mutations that belong to the 151 set in the absence of the pivotal Q151M substitution were detected in as many as 3.9% of the patients. One patient exhibited a 69S [VG] insert that has not been previously phenotypically characterized. This HIV-1 isolate had high levels of resistance to all NRTIs except stavudine. MddNR is an emerging problem after sequential therapy with this class of compounds among HIV-1-infected patients. Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex. Monotherapy with ZDV and ddI or subsequent treatments with various NRTI combinations were the common background in the patients with the 69 insert. The overall prevalence of MddNR (3.4%) in Italy is comparable with that observed in several other European countries (3.4%-6.5%). These data suggest that patients failed by NRTI regimens should be analyzed for the presence of both patterns of MddNR.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Quantitative evaluation of the recombinant HIV-1 phenotype to protease inhibitors by a single-step strategy.

OBJECTIVE: To develop and optimize a fast and quantitative recombinant strategy for evaluating the HIV-1 phenotype to protease inhibitors (PI). DESIGN AND METHODS: A non-replicative HIV-1 molecular vector (designated pdelta prodelta env) capable of expressing exogenous HIV-1 protease-encoding sequences was developed in this study. The HIV-1 protease sequences were amplified from either viral isolates or plasma samples (both from 21 HIV-1-infected individuals, 19 of whom were failing different anti-HIV-1 combination treatments) and cloned in the pdelta prodelta env backbone. The HIV-1 recombinant phenotype to PI was determined directly after transfection of viral chimeric clones by measuring protease activity and calculating a percentage sensitivity index (SI%; the ratio between the results from each clone and those from a PI-sensitive reference strain). RESULTS: The SI% values obtained from the recombinant clones paralleled the IC50 results of the viral isolates and documented different degrees of resistance and cross-resistance to PI, compatible, with few exceptions, with the respective genotype. Interestingly, an inverse correlation between SI% values and the presence of primary mutations for resistance to PI (P = 0.0038 and P = 0.0414, for indinavir and ritonavir, respectively) and a difference in SI% between samples harbouring an increasing number of mutations (indinavir, P = 0.022; ritonavir, P = 0.0466) were observed. CONCLUSION: The data substantiate the reliability of the novel strategy for a fast (5 day) quantitative evaluation of HIV-1 phenotype to PI, and indicate that this method may contribute to the understanding of mechanisms of virus resistance to PI.

Chimera↗
PubMed2000

Competition of annexin V and anticardiolipin antibodies for binding to phosphatidylserine containing membranes.

Annexin V, an intracellular protein with a calcium-dependent high affinity for anionic phospholipid membranes, acts as an inhibitor of lipid-dependent reactions of the blood coagulation. Antiphospholipid antibodies found in the plasma of patients with antiphospholipid syndrome generally do not interact with phospholipid membranes directly, but recognize (plasma) proteins associated with lipid membranes, mostly prothrombin or beta(2)-glycoprotein I (beta(2)GPI). Previously, it has been proposed that antiphospholipid antibodies may cause thrombosis by displacing annexin V from procoagulant cell surfaces. We used ellipsometry to study the binding of annexin V and of complexes of beta(2)GPI with patient-derived IgG antibodies to beta(2)GPI, commonly referred to as anticardiolipin antibodies (ACA), to phospholipid bilayers composed of phosphatidylcholine (PC) and 20% phosphatidylserine (PS). More specifically, we investigated the competition of these proteins for the binding sites at these bilayers. We show that ACA-beta(2)GPI complexes, adsorbed to PSPC bilayers, are displaced for more than 70% by annexin V and that annexin V binding is unaffected by the presence of ACA-beta(2)GPI complexes. Conversely, annexin V preadsorbed to these bilayers completely prevents adsorption of ACA-beta(2)GPI complexes, and none of the preadsorbed annexin V is displaced by ACA-beta(2)GPI complexes. Using ellipsometry, we also studied the effect of ACA-beta(2)GPI complexes on the interaction of annexin V with the membranes of ionophore-activated blood platelets as a more physiological relevant model of cell membranes. The experiments with blood platelets confirm the high-affinity binding of annexin V to these membranes and unequivocally show that annexin V binding is unaffected by the presence of ACA-beta(2)GPI. In conclusion, our data unambiguously show that ACA-beta(2)GPI complexes are unable to displace annexin V from procoagulant membranes to any significant extent, whereas annexin V does displace the majority of preadsorbed ACA-beta(2)GPI complexes from these membranes.

Annexin A5↗
PubMed2000

Should we include anti-prothrombin antibodies in the screening for the antiphospholipid syndrome?

Anti-prothrombin antibodies belong to the family of the antiphospholipid antibodies. Their prevalence ranges from 50 to 90% of antiphospholipid-positive patients, depending on the laboratory methodology employed for their detection. ELISA techniques are the most commonly used methods for their measurements, which allow a quick determination of their titer and isotype(s). Unfortunately, no well standardized assays are yet commercially available. The clinical relevance of anti-prothrombin antibodies as risk factors for thromboembolic events has been investigated by a number of retrospective and case-control studies. We reviewed 11 studies: data on 1,440 patients and 371 sex- and age-matched controls were available. Seven studies reported a significant association between anti-prothrombin antibodies and thrombosis by univariate analysis. Multivariate analysis was performed in five studies: only two of them confirmed the association. The sensitivity and specificity of anti-prothrombin antibodies for thrombosis were analysed according to the antibody isotype and to the arterial and/or venous site of thrombosis. The sensitivities are disappointingly low, particularly when the M isotype and arterial thrombosis are considered, whereas the specificities are somewhat better, even though they range widely. These data do not allow to recommend the measurement of anti-prothrombin antibodies in the routine laboratory workout of antiphospholipid-positive patients in order to define their thrombotic risk.

Antibodies, Antiphospholipid↗