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Biomedical subjects

M Galli

Publications and source records attributed to M Galli.

At least 73 records · Page 4Linked to original sources
PubMed2000

The G1691 --> A mutation of factor V, but not the G20210 --> A mutation of factor II or the C677 --> T mutation of methylenetetrahydrofolate reductase genes, is associated with venous thrombosis in patients with lupus anticoagulants.

Arterial and venous thrombosis are the most common manifestations of antiphospholipid syndrome. To investigate whether genetic determinants contribute to their thrombotic risk, we studied the prevalence of the G1691 --> A mutation in the gene coding for factor V, the G20210 --> A mutation in the prothrombin gene and the C677 --> T mutation in the methylenetetrahydrofolate reductase gene in 152 patients with lupus anticoagulants. One hundred and twenty-eight cases (84%) also had increased titres of anticardiolipin antibodies. History of thrombosis was present in 96 patients (63%); 67 suffered from venous thrombosis only, 23 cases had arterial thrombosis only, six patients had both venous and arterial thrombosis. Five patients were heterozygous for the G1691 --> A mutation in the factor V gene (3%). All of them (100%) suffered from venous thrombosis compared with 68 out of the 147 cases without the mutation (46%) (P = 0.0474). The prevalence of the G20210 --> A mutation in the prothrombin gene was evaluated in 145 patients; eight of these patients were heterozygous (5%). Four of these patients (50%) experienced venous thrombosis compared with 65 out of the 137 patients without the mutation (47%) (P = ns). Neither mutation was associated with arterial thrombotic events. No patient carried both mutations. The C677 --> T mutation in the methylenetetrahydrofolate reductase gene was assessed in 83 patients; 15 of them (18%) were homozygous and 37 (44%) were heterozygous. There was no significant association between the status of the mutation and history of venous and arterial thrombosis. No significant correlation was found among the three groups. In conclusion, only the G1691 --> A mutation in the factor V gene was associated with the thrombotic risk of patients with lupus anticoagulants.

Antibodies, Anticardiolipin↗
PubMed2000

Post-kala-azar dermal leishmaniasis during highly active antiretroviral therapy in an AIDS patient infected with Leishmania infantum.

We report a case of post-kala-azar dermal leishmaniasis (PKDL) in a woman with AIDS which occurred 13 months after a diagnosis of visceral leishmaniasis concomitantly with immunological recovery induced by highly active retroviral therapy. Cytokine pattern at the time of visceral leishmaniasis and PKDL diagnosis was studied and pathogenic implications were discussed.

Adult↗
PubMed2000

Body habitus alterations in HIV-infected women treated with combined antiretroviral therapy.

Fat distribution alterations are among the most frequent and unexpected side effects of combined antiretroviral therapy. They may occur in patients receiving protease inhibitor-containing regimens and those treated with combinations of only nucleoside reverse transcriptase inhibitors. The broad spectrum of body fat alterations, which are variably associated with metabolic abnormalities, raises the question as to whether they represent different components of the same syndrome or are manifestations of different pathogenetic mechanisms. Recent clinical evidence is consistent with a higher risk of developing body fat alterations in females. We here report three different aspects of body habitus changes in women treated with various antiretroviral regimens and describe their short-term follow-up. We also discuss the possible pathogenetic implications and the role of different drug classes according to present knowledge.

Adult↗
PubMed2000

Fat redistribution in HIV-infected patients. A new hormonal-immune disorder?

Multidrug antiretroviral regimes in HIV-infected patients may have side effects. The most frequent side effects are changes in fat metabolism and distribution. We describe a particular pattern of fat redistribution (FR), characterized by a progressive enlargement of breast and abdominal girth and fat loss in the lower limbs, which occurs in approximately 10% of HIV-infected women treated with combined antiretroviral therapy. To elucidate the metabolic, endocrine, and immunologic consequences of the observed disturbance, we measured serum lipids, glucose, C-peptide, ACTH, plasma, urinary cortisol, and cytokines IL-2, IFN gamma, Il-4, IL-10, Il-12, and TNF alpha in 36 patients with FR and in a control group without FR. There were no significant differences in hormonal and metabolic laboratory testing between the two groups. Immunology studies showed that in vitro production of TNF alpha and IL-10 was lower and IL-12 production higher in SR patients. Whether or not such immune alterations may be reponsible or be caused by fat redistribution remains to be explained. One year after the follow up, 50% of the patients treated with triple therapy developed lipodystrophy, characterized by weight loss, face-wasting, and hyperglycemia; the remaining 50% remained unchanged. In 13 patients the 3TC withdrawal was followed by improvements of the syndrome in 50% and of lipodystrophy in about 25%. These data suggest that the FR syndrome is frequent in patients treated with 3TC and that it is associated with characteristic changes in the cytokine production.

Adult↗
PubMed2000

Immunoendocrinologic abnormalities in human immunodeficiency virus infection.

Alterations in the production of adrenal steroids and a complex pattern of dysregulation in cytokine profiles accompany the progression of HIV infection. Cortisol levels increase in HIV infection, while those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the immunoregulatory activities of cortisol, decrease. A shift from type-1 to type-2 cytokine production is also detected in most patients during disease progression. This shift is summarized as a defective production of interferon gamma (IFN gamma), interleukin-2 (IL), and IL-12 accompained by increased production of IL-4, IL-5, IL-6, and IL-10. IFN gamma and IL-2 are suppressed, while the generation of IL-4 is stimulated by cortisol and pharmacological doses of glucocorticoids (GC). GC and IL-4 stimulate the differentiation of B lymphocytes into IgE-producing plasma cells, the concentration of which augments in HIV infection. Finally, GC induces programmed cell death (PCD) in a variety of different cells, including mature T lymphocytes. Because (1) TH1 but not TH2 undergo rapid Fas-mediated PCD upon antigen-stimulation, and (2) TH2 clones preferentially survive in vitro cell cultures, the progressive shift from type-1 to type-2 cytokine production observed in HIV infection could be at least partially provoked by the increase in the production of cortisol and the reduction of DHEA. Progression of HIV infection to AIDS can be controlled by highly active antiretroviral therapy (HAART); HAART drastically reduces HIV plasma viremia, but is less effective in immune reconstitution. Additionally HAART is associated in a sizable portion of patients by complex lypodistropyc phenomena that often involve the endocrine system.

HIV Infections↗
PubMed2000

Susceptibility to PNU-140690 (Tipranavir) of human immunodeficiency virus type 1 isolates derived from patients with multidrug resistance to other protease inhibitors.

In our study we examined the anti-human immunodeficiency virus type 1 (anti-HIV-1) activity of a novel HIV-1 protease inhibitor, PNU-140690 (tipranavir), against patient-derived isolates resistant to multiple other protease inhibitors (PIs). The aim of our experiments was to investigate the genotypes and the in vitro phenotypes of drug resistance of PNU-140690. We carried out drug susceptibility tests with peripheral blood mononuclear cells and a fixed amount of infectious virus (1,000 50% tissue culture infective doses) to determine the 50% inhibitory concentration (IC(50)) and IC(90), PCR assays for the detection of drug resistance mutations in RNA in plasma, and direct sequencing of PCR products. Phenotypic resistance to PIs was invariably related to genotypic mutations. The substitutions among the amino acid residues of the protease included L10I, K20R, L24I, M36I, N37D, G48V, I54V, L63P, I64V, A71V, V77I, V82A, I84V, and L90M. Isolates from all of the patients had developed a maximal degree of resistance to indinavir, ritonavir, and nelfinavir (IC(50)s, >0.1 microM). We also compared these mutations with the amino acid changes previously described in association with in vivo tipranavir administration. The mutations included the following: I15V, E35D, N37D, R41K, D60E, and A71T. Infections with IIIB, 14aPre, and N70 were inhibited by an average drug IC(90) of 0.18 +/- 0.02 microM in multiple experiments. The average mean +/- standard error of mean IC(90) for the entire group of multidrug-resistant isolates derived from the mean values for two culture wells with p24 antigen supernatant appeared to be 0.619 +/- 0.055 microM (range, 0.31 to 0.86 microM). Tipranavir retained a sustained antiviral activity against PI-MDR clinical isolates and might be useful in combination regimens with other antiretroviral agents for patients who have already failed other PI-containing therapies.

Anti-HIV Agents↗
PubMed2000

Combination of CCR5 and CXCR4 inhibitors in therapy of human immunodeficiency virus type 1 infection: in vitro studies of mixed virus infections.

We studied the combined anti-human immunodeficiency virus type 1 (HIV-1) effects of a derivative of stroma-derived factor 1beta (SDF-1beta), Met-SDF-1beta, and a modified form of RANTES, aminooxypentane (AOP)-RANTES. The antiviral agents were tested singly or in combination at 95 and 99% virus inhibitory concentrations. Clinical R5 and X4 HIV-1 isolates were used. AOP-RANTES inhibited R5 but not X4 viruses, whereas Met-SDF-1beta had the opposite effect. Combinations of these compounds inhibited mixed infections with R5 and X4 viruses (95 to 99%), whereas single drugs were less inhibitory (32 to 61%). Combinations of R5 and X4 inhibitors are promising and deserve further evaluation.

Amino Acid Sequence↗
PubMed2000

Which antiphospholipid antibodies should be measured in the antiphospholipid syndrome?

The results of an analysis of studies published over a 10-year period that addressed the association between antiphospholipid antibodies (aPLs) and thromboembolic events in patients with the antiphospholipid syndrome (APS) are reported. It would appear that lupus anticoagulants are the strongest risk factor for thromboembolic events in aPL-positive patients. Consequently, it is suggested that all patients with clinical manifestations of APS should be tested for these antibodies. On the other hand, the results do not unequivocally show that measurement of anticardiolipin antibodies is of help in defining the thrombotic risk of patients. Furthermore, they only partially support the notion that anti-beta 2-glycoprotein I and antiprothrombin antibodies may be independent risk factors for thrombosis.

Antibodies, Anticardiolipin↗
PubMed2000

[The clinical use of the GPIIb/IIIa inhibitors eptifibatide and tirofiban in the treatment of acute coronary syndromes of the "non-ST elevation" type].

Acute coronary syndromes not associated with ST-segment elevation, i.e. unstable angina and non-Q wave myocardial infarction, represent a heterogeneous group of clinical disorders sharing similar pathogenic mechanisms, clinical presentation and medical management. Current guidelines recommended an early anti-thrombotic and anti-ischemic treatment in these patients, as well as their prompt risk evaluation based on easily available clinical and instrumental data, to identify those subjects at greater risk in whom a more aggressive management is warranted. Despite the association of aspirin, heparin and anti-ischemic drugs, the 30-day rate of death or myocardial infarction remains high (9-15%) in patients with markers of greater risk (i.e. Braunwald class III, ST-segment depression, abnormal creatine kinase or troponin values). Moreover, in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI), complex coronary lesions increase the peri-procedural risk of thrombotic complications. Regardless of the agonist responsible for platelet activation and aggregation, platelet glycoprotein (GP) IIb/IIIa receptor activation is the key factor in thrombosis formation. Several clinical trials in the past few years have documented the beneficial value of GP IIb/IIIa inhibitors in patients treated with aspirin and heparin, with a significant reduction in the cumulative end-point of death and/or myocardial infarction at 48-96 hours (odds ratio--OR 0.81, 95% confidence interval--CI 0.71-0.92, p < 0.01). Such therapeutical benefit is still present at 30 days (OR 0.88, 95% CI 0.81-0.97, p < 0.001) and 6 months (OR 0.88, 95% CI 0.79-0.97, p < 0.001). In patients treated with abciximab, eptifibatide or tirofiban, undergoing early PCI, a remarkable relative reduction in the risk of death and non-fatal acute myocardial infarction was shown before PCI (-34%, p < 0.001). The pre-PCI administration of GP IIb/IIIa inhibitors is associated with a significant reduction in peri-procedural complications (-41% relative reduction of death or acute myocardial infarction in the 48 hours after PCI, p < 0.001). In this subset of patients the benefit correlates with abnormal pre-PCI values of troponin, a reliable surrogate marker of active thrombosis. The greatest clinical benefit from GP IIb/IIIa inhibitors is expected in patients presenting high-risk features (early post-infarction angina; older age with a history of left ventricular dysfunction or diabetes; heart failure symptoms, ST-segment depression, abnormal troponin, creatine kinase, and C-reactive protein values at admission) as well as in patients with recurrent ischemic attacks and those undergoing early PCI. Although the combination of GP IIb/IIIa inhibition and standard doses of unfractionated heparin is associated with an increased risk of major bleeding, such risk can be remarkably reduced adopting simple technical suggestions.

Acute Disease↗
PubMed2000

Transcatheter mechanical thrombus aspiration for stent thrombosis.

Currently, in-stent thrombosis is a rare but serious clinical event. The mechanical or pharmacological approach has not totally solved this problem. In this report we describe the treatment of in-stent thrombosis with a new device for mechanical thrombus aspiration. We used the Rescue catheter (Rescue Catheter System, Boston Scientific), a new 4.5F dual lumen monorail catheter that was able to break and aspirate thrombus without evidence of distal embolization. In this case the procedure was quickly performed with good angiographic results after mechanical aspiration and additional traditional coronary angioplasty. Moreover, the excellent clinical outcome confirmed the efficacy of the technique in the percutaneous treatment of this late complication of stent implantation.

Cardiac Catheterization↗
PubMed2000

Prevalence of transmitted nucleoside analogue-resistant HIV-1 strains and pre-existing mutations in pol reverse transcriptase and protease region: outcome after treatment in recently infected individuals.

We retrospectively studied 38 Italian recently HIV-1-infected subjects who seroconverted from 1994 to 1997 to investigate: (i) the prevalence of nucleoside reverse transcriptase inhibitors (NRTI)-related mutations at primary infection; (ii) the proportion of naturally occurring mutations in reverse transcriptase (RT) and protease regions of patients naive for non-nucleoside RT inhibitors (NNRTIs) and protease inhibitors (PIs); (iii) the drug-susceptibility to NRTIs and PIs in subjects with NRTI- and/or PI-related mutations; and (iv) the outcome of seroconverters treated with various NRTIs or NRTI/PI regimens. Baseline HIV-1 plasma viraemia and absolute CD4 count at baseline could not be used to distinguish patients with NRTI- and/or PI-related pre-existing mutations from those with wild-type virus (P = 0.693 and P = 0.542, respectively). The frequency of zidovudine-related mutations was 21% in the study period. The response to treatment was not significantly different in subjects with or without genotypic zidovudine-related mutations at primary infection (P = 0.744 for HIV-1 RNA and P = 0.102 for CD4 cells). Some natural variation (2.6%) was present within regions 98-108 and 179-190 of RT involved in NNRTI resistance. The high natural polymorphism in the protease region present in our patients was similar to that reported by others. In our study some PI-associated substitutions, thought to be compensatory in protease enzymatic function, could confer intermediate to high PI-resistance. As discrepancies between genotypic and phenotypic results may exist in recent seroconverters, our data suggest that the role of transmitted NRTI- and PI-resistant variants remain to be fully elucidated in vivo.

Anti-HIV Agents↗
PubMed2000

Persisting HIV-1 replication triggered by acute hepatitis A virus infection.

We report the case of two patients in whom acute hepatitis A was associated with a marked and prolonged increase in human immunodeficiency virus type 1 (HIV-1) viral load. Although in one patient the rise in HIV-1 RNA might also have been related to the interruption of antiretroviral therapy, we also observed a similar pattern in the other patient who had a stable undetectable plasma viraemia prior to acute hepatitis and never received treatment with anti-retrovirals. Our observation supports the hypothesis that immune activation that is induced by acute hepatitis A virus (HAV) infection may trigger HIV-1 replication. This highlights the importance of maintaining antiretroviral therapy throughout the acute phase of hepatitis A and of preventing HAV infection through active immunization.

Adult↗
PubMed2000

Italian BiodivYsio open registry (BiodivYsio PC-coated stent): study of clinical outcomes of the implant of a PC-coated coronary stent.

UNLABELLED: Rapid technological developments have made new materials available for percutaneous coronary intervention procedures. The coronary stent in particular has undergone progressive structural improvements leading to the recent availability of a third generation of stents, namely, coated stents. The rapid evolution of the stent has often made its evaluation problematical, since trials are frequently confined to small groups of patients in single centers. The purpose of this registry was to verify the safety and efficacy of the BiodivYsio stent (a stent coated with phosphorylcholine polymer) in a broad population of patients who reflect the daily reality of coronary intervention in a cardiac catheterization laboratory. METHODS AND RESULTS: The registry was designed to collect the principal angiographic and clinical data of a consecutive series of Oreal worldO patients. Patients were treated with a BiodivYsio stent (Biocompatibles, Galway, United Kingdom) in 12 centers (11 Italian and 1 Swiss) between January 1998 and January 1999. Procedural, in-hospital, 30-day and six-month follow-up data were collected. The monitoring, data entry and statistical analyses were carried out by an independent center. During the study, 218 patients were enrolled; 165 (76%) male and 53 (24%) female, with an average age of 61.6 +/- 9.4 years (range, 36Eth 84 years). A total of 258 stents were implanted in 233 lesions (1.1 stents per lesion), of which 233 (90%) were the BiodivYsio PC coated stent, the remaining 25 implants were of other stent types. The percutaneous transluminal coronary angioplasty and stenting procedure were carried out in 109 (50%) patients with unstable angina, 65 (30%) with stable angina, 29 (13%) with acute myocardial infarction, and 15 (7%) patients with silent ischemia. Procedural success was achieved in 217/218 (99.5%) patients. Optimal results were achieved in 212 (97.7%) patients. In 34 (15.6%) cases, patients were treated with periprocedural abciximab. During the hospitalization period, one (0.4%) death occurred on day 7 due to subacute occlusion of the stent, and 3 (1.4%) myocardial infarctions were reported. At 30-day follow-up, 211 (97.2%) patients were asymptomatic, as were 189 (87%) patients at clinical follow-up at 6 months. CONCLUSIONS: This study evaluated the safety and efficacy of a third-generation stent. The results demonstrate a high procedural success rate and a low incidence of major adverse cardiac events at short- and medium-term follow-up. It appears that the BiodivYsio stent should be considered safe in clinical and/or anatomical situations with a high risk of complications, confirming the hypothesis that PC may have non-thrombogenic properties. To corroborate these results, an appropriately designed study would be required to measure the stentOs efficacy in the most suitable clinical context, i.e., clinical situations that are at the highest risk of ischemic relapse.

Adult↗
PubMed2000

Antibodies to beta2-glycoprotein I associated with antiphospholipid syndrome suppress the inhibitory activity of tissue factor pathway inhibitor.

Anionic phospholipid membranes have a dual role in blood coagulation: they are essential for the initiation and propagation as well as for the limitation and termination of the blood coagulation process. Patients with the anti-phospholipid syndrome (APS) carrying antibodies against complexes of anionic phospholipids and plasma proteins, show in vitro inhibited phospholipid dependent coagulation reactions, whereas in vivo the presence of these antibodies is associated with an increased risk of thrombosis. In this study we focussed on the effects of these anti-phospholipid antibodies on the regulation of TF-mediated factor Xa (FXa) generation in plasma. We hypothesized that anti-phospholipid antibodies interfere with the phospholipid-dependent inhibition by tissue factor pathway inhibitor (TFPI) of TF-induced coagulation. Indeed, total-IgG, anti-cardiolipin-IgG (aCL) and anti-beta2GPI-IgG, isolated from patient plasmas, all stimulated TF-induced FXa generation in normal plasma. This enhanced FXa generation was not observed when the patient's IgG was depleted of anti-beta2GPI-IgG or when normal plasma was depleted of beta2PGPI or TFPI. Taken together, these data indicate that antibodies to beta2GPI, circulating in patients with APS, suppress TFPI-dependent inhibition of TF-induced coagulation, which results in an increased FXa generation.

Antiphospholipid Syndrome↗
PubMed2000

In vitro inhibition of HIV-1 by Met-SDF-1beta alone or in combination with antiretroviral drugs.

Compounds that can block the CXCR4 chemokine receptor are a promising new class of antiretroviral agents. In these experiments we studied the effect of a modified form of the native stromal cell-derived factor-1 (SDF-1), Met-SDF-1beta. The in vitro susceptibility of two different CXCR4-tropic HIV-1 strains was determined. Antiviral effect was assessed by the reduction of p24 antigen production in PHA-stimulated peripheral blood mononuclear cells with exposure to the modified SDF-1 molecule. The 50% inhibitory concentrations (IC50) were derived from six separate experiments. The IC50 against the two HIV-1 isolates was in 1.0-2.8 microg/ml range for Met-SDF-1beta. Met-SDF-1beta showed synergy to additivity with either zidovudine or nelfinavir at IC75 IC90 and IC95. Additivity was seen when Met-SDF-1beta was combined with efavirenz. No cellular toxicity was observed at the highest concentrations when these agents were used either singly or in combination. This compound is a promising new candidate in a receptor-based approach to HIV-1 infection in conjunction with currently available combination antiretroviral drug therapies.

Anti-HIV Agents↗
PubMed2000

Lupus anticoagulants and thrombosis: clinical association of different coagulation and immunologic tests.

The dilute Russell's viper venom time (dRVVT) and the kaolin clotting time (KCT) are two among the most commonly used coagulation tests for the detection of lupus anticoagulants. The dRVVT seems superior to the KCT in identifying LA-positive patients at risk of thrombosis. However, this relationship is greatly influenced by both the source of reagents and the instrumentation employed to carry out the assays. Therefore, 4 dRVVTs ("home-made" dRVVT, DVV test, Bioclot LA, LA Screen), and one KCT (Kaoclot) were performed in two centers and compared for their retrospective correlation with the thrombotic complications of 72 patients with a previously established diagnosis of lupus anticoagulants. Two other assays ("home-made" KCT, and Colloidal Silica Clotting Time, CSCT) were performed in one of the two centers, and compared with Kaoclot for their clinical correlations in the same population of patients, 44 of whom (61%) had suffered from arterial and/or venous thrombosis. A rather good degree of inter-laboratory and inter-assay correlations of the different tests was found. However, a statistically significant association with thrombosis was found only with the coagulation profile generated using the "home-made" dRVVT. When the commercially available dRVVTs were used, none of the coagulation profiles remained associated with thrombosis. When the assays were analyzed separately, the association with thrombosis was statistically significant for LA screen (p = 0.0019), DVV test (p = 0.0043), and Bioclot (p = 0.0255), and of borderline significance for the "home-made" dRVVT (p = 0.0503) in one center. This last assay was also significantly associated with thrombosis in the other center (p = 0.0139). When venous and arterial thrombosis were considered separately, DVV test was statistically associated with venous thrombosis in both centers (p = 0.0076 and p = 0.0187, respectively), and LA screen in one center (p = 0.0303). No dRVVT was found to correlate with arterial thrombosis. Kaoclot, Colloidal Silica Clotting Time, and the "home-made" KCT did not correlate with thrombosis. The prevalence of IgG and/or IgM antibodies to cardiolipin, beta2-glycoprotein I and prothrombin were 74%, 86% and 85%, respectively. Increased titers of IgG anticardiolipin antibodies were associated with arterial thrombosis (p = 0.0375), whereas IgM anti-beta2-glycoprotein I antibodies were associated with venous thrombosis (p = 0.0433). In conclusion, these retrospective data support the notion that the dRVVT, rather than other coagulation or ELISA tests, are able to identify lupus anticoagulant-positive patients at risk of thrombosis. This property appears common to several commercially available dRVVT kits, making this type of assay the ideal target of future efforts of laboratory standardization.

Adult↗