MHC class II and III polymorphisms and the antiphospholipid syndrome.
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Biomedical subjects
Publications and source records attributed to M Galli.
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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.
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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.
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.
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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.
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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.
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.
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.
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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.
Proliferating cell nuclear antigen (PCNA) is one of the cell cycle-related proteins directly involved in DNA synthesis. It is a marker of cellular proliferation and has been shown to correlate with ploidy and proliferative activity of cells. Its expression has been used to estimate the growth fraction of human cancer and its prognostic value. Pigmented villo-nodular synovitis (PVNS) is characterised by a nodular lesion in the paratendinous synovial tissue or, less frequently, in a joint. Whether PVNS is a neoplastic or inflammatory lesion remains controversial. We have studied immunohistochemical PCNA expression with pc10 monoclonal antibody in 16 paraffin sections, in 16 cases of localised PVNS, or giant cell tumour of tendon sheath. We have found significant correlation between the size of the lesions and PCNA-LI (labelling index).
We evaluated [(11)C]fluvoxamine as a tracer for the serotonin re-uptake site. Studies of the distribution of the tracer in rat and primate brain showed adequate uptake of [(11)C]fluvoxamine, but failed to reveal regions with known high density of serotoninergic re-uptake sites. Pretreatment with unlabeled fluvoxamine did not substantially change the distribution. In rat brain tissue, nearly all radioactivity represented intact [(11)C]fluvoxamine. [(11)C]Fluvoxamine does not function as a tracer for serotonin re-uptake sites, owing to high nonspecific binding in the brain.
OBJECTIVES: The aim of this study was to evaluate the typical strategies of obese subjects during a sit-to-stand task (a typical daily living activity) and to assess the load conditions of hip, knee and ankle joints. DESIGN: Cross-sectional, controlled (obese patients vs controls) study on sit-to-stand movement analysis SUBJECTS: Ten adult young volunteers (five men and five women, mean age 28, s.d. 3 y; mean BMI 22, s.d. 2.3 kg/m2) and 30 obese subjects 25 women and five men, mean age 39.4, s.d. 13.7 y, mean BMI 40, s.d. 5.9 kg/m2) suffering from chronic lower back pain were analyzed in a sit-to-stand task (10 trials for each subject). MEASUREMENTS: Angle parameters carried out from a quantitative three-dimensional analysis of sit-to-stand (STS) movement, using an optoelectronic system. RESULTS: STS task in controls was characterized by a fully forward bending strategy of the trunk, while in obese patients at the beginning (first trial) of the STS task they limited the forward bending in order to protect the vertebral column. When fatigue increased during the execution of multiple STS tasks, the protection of the vertebral column was secondary to the execution of the task. In order to limit the muscle fatigue they increased the forward bending in order to decrease knee joint torque. DISCUSSION: The analysis of the strategy used by obese patients in STS task can be used in the design of future trials to assess the efficacy of rehabilitative treatment.
A reduction in fibrinolysis has been described in association with thrombosis in the primary antiphospholipid syndrome (PAPS). In this study, we measured anti-tissue-type plasminogen activator (t-PA) antibodies and anti-fibrin-bound t-PA antibodies as possible causes of hypofibrinolysis in 39 patients with PAPS. We also evaluated the differences in anti t-PA antibodies between patients without previous thrombosis (20 patients) and patients with previous episodes of thrombosis (19 patients: deep vein thrombosis in nine, ischaemic stroke in six, arterial leg thrombosis in one, hepatic vein thrombosis in one, thrombophlebitis in one and cerebral venous thrombosis in one). Anti-t-PA antibodies were measured by an enzyme-linked immunosorbent assay (ELISA), and anti-t-PA fibrin-bound antibodies were measured by a solid-phase fibrin immunoassay (SOFIA) in 39 patients with PAPS and in 39 controls matched for gender and age. High levels of IgG anti-t-PA were found in three out of 39 patients with PAPS, and all three patients had a history of thrombosis; four other patients, one of whom had a history of thrombotic events, had high titres of antibodies directed against fibrin-bound t-PA. In addition, patients with ischaemic stroke had significantly higher levels of IgG anti-t-PA than patients without thrombosis (P = 0.029). In conclusion, our data showed that, in patients with PAPS, the highest levels of anti-t-PA antibodies were present in subjects with previous thrombotic events. The discrepancy in the results obtained with two methods of detection of anti-t-PA antibodies, ELISA and SOFIA, indicates a different interaction of the antibodies with the t-PA molecules, which are directly bound to polystyrene plates in ELISA and bound to fibrin as a bridging molecule in SOFIA.