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Biomedical subjects

Marc Lambert

Publications and source records attributed to Marc Lambert.

10 recordsLinked to original sources

Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing coronary stenting.

OBJECTIVES: We analyzed the benefit of a 600-mg clopidogrel loading dose on platelet reactivity and clinical outcomes after stenting for non-ST-segment elevation acute coronary syndrome (NSTE ACS). BACKGROUND: High post-treatment platelet reactivity (HPPR = adenosine diphosphate 10 mumol x l(-1) [ADP]-induced platelet aggregation >70%) is a marker for low responders to dual antiplatelet therapy with increased risk of recurrent cardiovascular (CV) events after stenting for NSTE ACS. METHODS: A total of 292 consecutive NSTE ACS patients undergoing coronary stenting were included and randomly received a 300-mg (n = 146) or 600-mg (n = 146) loading dose of clopidogrel at least 12 h before percutaneous coronary intervention. A single post-treatment blood sample was obtained before percutaneous coronary intervention to analyze maximal intensity of ADP-induced platelet aggregation and platelet surface expression of P-selectin. One-month follow-up CV events were recorded. RESULTS: The ADP-induced platelet aggregation and expression of P-selectin were significantly lower in patients receiving 600 mg than in those receiving 300 mg (mean +/- SD: 50 +/- 19% vs. 61+/- 16%, p < 0.0001 and 0.38 +/- 0.24 arbitrary units vs. 0.60 +/- 0.40 arbitrary units; p < 0.0001 respectively). Persistence of HPPR was less common in patients receiving 600 mg than in those receiving 300 mg (15 vs. 25%, p = 0.03). During the 1-month follow-up, 18 CV events (12%) occurred in the 300-mg group versus 7 (5%) in the 600-mg group (p = 0.02); this difference was not affected by adjustment for conventional CV risk factors (p = 0.035). CONCLUSIONS: In NSTE ACS patients undergoing coronary stenting, a 600-mg loading dose of clopidogrel shows its benefit on platelet reactivity and clinical prognosis.

Aged↗

Recovery from deafness in a patient with Muckle-Wells syndrome treated with anakinra.

Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory disease characterized by rashes, fever, arthralgia, sensorineural deafness, and the possible development of systemic AA amyloidosis. We used anakinra to treat a 22-year-old patient with MWS who had deafness and a high serum level of C-reactive protein (CRP). Following treatment with anakinra, the patient's CRP level normalized, and she recovered from deafness. The fact that this occurrence has never been previously reported strengthens the role of anakinra in MWS but also raises new questions about the physiopathology of such deafness.

Adult↗

[Takayasu arteritis].

Takayasu arteritis is an inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Thickening of the vessel wall is an early hallmark of the disease and leads to stenosis, thrombosis, and sometimes aneurysm formation. Reported incidence ranges from 1.2 to 2.6/million/year. Women aged 20 to 40 are most likely to suffer from the disease than men. Manifestations are very polymorphous, with presentations ranging from asymptomatic to neurologic catastrophes. Prognosis depends essentially on complications (retinopathy, hypertension, aneurysm, aortic insufficiency) and initial disease aggressivity. Diagnosis is based on imaging methods. Doppler ultrasound, computed tomography, and magnetic resonance imaging are fast and reliable methods for assessing vessel anatomy and luminal status. Positron emission tomography with fluorodeoxyglucose appears to be a highly sensitive and effective method for detecting disease activity, especially since standard inflammatory markers seem ineffective. Until now, corticosteroids have been the treatment of choice. If remission does not occur, methotrexate is added. Percutaneous transluminal angioplasty and sometimes vascular surgery is necessary in cases of critical ischemia or threatening aneurysm. Duration of treatment, choice of second-line treatment, and protocol for tapering medication currently depend more on experience than on evidence-based medicine. Multicenter studies are needed to guide future practice.

Diagnosis, Differential↗

Significance of persistent antiphospholipid antibodies in the elderly.

OBJECTIVE: The prevalence of anticardiolipin antibodies (aCL) and of vascular diseases increases with age, and aCL may be associated with various diseases in the elderly. So the significance of aCL in the elderly remains difficult to determine. We sought to determine the significance of persistent antiphospholipid antibodies (aPL) in the elderly. METHODS: We retrospectively analyzed the files of 327 patients [149 patients with antiphospholipid syndrome (APS); 64 patients age >or= 65 yrs] with 2 positive aPL [lupus anticoagulant (LAC) and/or aCL]. RESULTS: The frequency of APS was 40.8% (n = 134) in our 263 young patients (< 65 yrs) and 23.4% (n = 15) in our 64 elderly patients (>or= 65 yrs). The clinical characteristics of patients with persistent aPL were the same in those under and over 65 years. LAC was positive in all but one elderly patient with APS, and occurred in this group more frequently than in the young patients (93.3% vs 44.6%; p < 0.006). The presence of LAC allowed to discriminate APS patients in our elderly population (93.3% in APS vs 48.9% in non-APS patients; p < 0.009). CONCLUSION: Interpretation of a positive determination of APL is difficult in the elderly; persistent LAC may be the most valuable biological marker of APS in the elderly.

Aged↗

High resolution computed tomography in fibrosing alveolitis associated with systemic sclerosis.

OBJECTIVE: To investigate the use of high resolution computed tomography (HRCT) in diagnosis of patients with fibrosing alveolitis associated with systemic sclerosis (FA-SSc), and to determine predictors of disease progression. METHODS: We retrospectively studied 90 patients with SSc who had undergone an initial (Time 1) and followup (Time 2) clinical and HRCT evaluation, with a mean +/- SD interval of 5.14 +/- 2.98 years between T1 and T2. RESULTS: At T1, HRCT was normal in 40 patients; at T2, 34/40 (85%) continued to have a normal HRCT. For the 50 patients with FA-SSc on HRCT scan at T1, the overall disease progression comprised extension of lung changes toward the apices with worsening of lung fibrosis at T2. Among the 37 patients who had areas of isolated ground-glass opacities at T1, 25 (68%) had progression of lung fibrosis at T2. These 25 patients were mostly men, who showed a more marked decrease of diffusing capacity and a longer interval between T1 and T2. CONCLUSION: The results emphasize the good longterm prognosis indicated by a normal initial HRCT in SSc. Patients with FA-SSc with abnormal HRCT experienced progressive replacement of ground-glass opacities by honeycombing and/or traction bronchiectasis/bronchiolectasis. Ground-glass opacity is probably the first step of lung fibrosis in SSc, and treatment should be discussed even at this early stage.

Adult↗

Prevalence of angiographic coronary artery disease in patients hospitalized for acute diastolic heart failure without clinical and electrocardiographic evidence of myocardial ischemia on admission.

The prevalence of coronary artery disease was investigated in 18 patients hospitalized for acute diastolic heart failure without clinical and electrocardiographic evidence of myocardial ischemia on admission. On the basis of coronary angiography, 7 patients had coronary artery disease and 4 had ischemic heart disease. In addition, besides uncontrolled hypertension and several systemic factors, silent myocardial ischemia potentially contributed to acute exacerbation of heart failure for at least 5 patients with coronary artery disease, according to either elevation in troponin I or segmental wall motion abnormalities.

Aged↗

The metalloprotease disintegrin ADAM8. Processing by autocatalysis is required for proteolytic activity and cell adhesion.

ADAMs (a disintegrin and metalloprotease domains) are metalloprotease and disintegrin domain-containing transmembrane glycoproteins with proteolytic, cell adhesion, cell fusion, and cell signaling properties. ADAM8 was originally cloned from monocytic cells, and its distinct expression pattern indicates possible roles in both immunology and neuropathology. Here we describe our analysis of its biochemical properties. In transfected COS-7 cells, ADAM8 is localized to the plasma membrane and processed into two forms derived either by prodomain removal or as remnant protein comprising the extracellular region with the disintegrin domain at the N terminus. Proteolytic removal of the ADAM8 propeptide was completely blocked in mutant ADAM8 with a Glu(330) to Gln exchange (EQ-A8) in the Zn(2+) binding motif (HE(330)LGHNLGMSHD), arguing for autocatalytic prodomain removal. In co-transfection experiments, the ectodomain but not the entire MP domain of ADAM8 was able to remove the prodomain from EQ-ADAM8. With cells expressing ADAM8, cell adhesion to a substrate-bound recombinant ADAM8 disintegrin/Cys-rich domain was observed in the absence of serum, blocked by an antibody directed against the ADAM8 disintegrin domain. Soluble ADAM8 protease, consisting of either the metalloprotease domain or the complete ectodomain, cleaved myelin basic protein and a fluorogenic peptide substrate, and was inhibited by batimastat (BB-94, IC(50) approximately 50 nm) but not by recombinant tissue inhibitor of matrix metalloproteinases 1, 2, 3, and 4. Our findings demonstrate that ADAM8 processing by autocatalysis leads to a potential sheddase and to a form of ADAM8 with a function in cell adhesion.

ADAM Proteins↗