Andre Manica

CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions

CD47 plays an important but incompletely understood role in innate and adaptive immune responses. CD47 associates in cis with T-cell LFA-1 integrins and regulates expression of high-affinity conformations of both LFA-1 and VLA-4.

Bone Marrow–Derived Kruppel-Like Factor 10 Controls Reendothelialization in Response to Arterial Injury

Objective—The objective of this study was to investigate the role of Kruppel-like factor (KLF) 10, a zinc-finger transcription factor, in bone marrow (BM)–derived cell responses to arterial endothelial injury. Accumulating evidence indicates that BM-derived progenitors are recruited to sites of vascular injury and contribute to endothelial repair. Approach and Results—In response to carotid artery endothelial denudation, KLF10 mRNA expression was markedly increased in both BM and circulating lin− progenitor cells. To examine the specific role of KLF10 in arterial reendothelialization, we used 2 models of endothelial denudation (wire- and thermal-induced injury) of the carotid artery in wild-type (WT) and KLF10−/− mice. WT mice displayed higher areas of reendothelialization compared with KLF10−/− mice after endothelial injury using either method. BM transplant studies revealed that reconstitution of KLF10−/− mice with WT BM fully rescued the defect in reendothelialization and increased lin−CD34+kinase insert domain receptor+ progenitors in the blood and injured carotid arteries. Conversely, reconstitution of WT mice with KLF10−/− BM recapitulated the defects in reendothelialization and peripheral cell progenitors. The media from cultured KLF10–/– BM progenitors was markedly inefficient in promoting endothelial cell growth and migration compared with the media from WT progenitors, indicative of defective paracrine trophic effects from KLF10–/– BM progenitors. Finally, BM-derived KLF10−/− lin− progenitors from reconstituted mice had reduced CXC-chemokine receptor 4 expression and impaired migratory responses. Conclusions—Collectively, these observations demonstrate a protective role for BM-derived KLF10 in paracrine and homing responses important for arterial endothelial injury and highlight KLF10 as a possible therapeutic target to promote endothelial repair in vascular disease states.

Stent Thrombosis: Understanding and Managing a Critical Problem

Opinion statementCoronary artery stent thrombosis (ST), defined as the thrombotic occlusion of a stented segment, is an infrequent but serious complication of percutaneous coronary intervention (PCI). The clinical consequences of ST are severe, because acute stent occlusion results in myocardial infarction and death in up to 45% of cases. Specific patient and procedural characteristics increase the risk of ST, but optimized interventional techniques and antiplatelet therapies have the potential to decrease ST and improve cardiovascular outcomes following PCI.

An Algorithm for use of Prasugrel (Effient) in Patients Undergoing Cardiac Catheterization and Percutaneous Coronary Intervention

An algorithm for use of Prasugrel (Effient) in patients undergoing cardiac catheterization and percutaneous coronary intervention at the Brigham and Womens Hospital is presented. Our algorithm, which is in the process of being implemented, is consistent with published and generally accepted standards of care and is based on data from the pivotal Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38, which compared clopidogrel with prasugrel in acute coronary syndrome patients undergoing percutaneous coronary intervention. Areas of focus include analysis of the benefit of prasugrel over clopidogrel in acute coronary syndrome patients and appropriate selection of patients for prasugrel treatment.

The role of depression in coronary artery disease

The concept of depression encompasses a series of psychopathological disorders that differ in regard to symptomatology, severity, course and prognosis. It is important to individualize these disorders for a better understanding of the following studies and of their diagnostic management. Major depressive disorder, as defined by CID X 1 and DSM IV , may have different clinical characteristics (table I). A specifier that may be employed in diagnosing the major depressive episode is the presence of melancholic symptoms (melancholia), whose main characteristic is the loss of interest and pleasure in all or almost all activities and a lack of reactivity to usually pleasant stimuli. In these circumstances, the depressive mood does not improve, not even temporarily, when something positive happens. Yet, at least three of the following symptoms should be present for the diagnosis of major depression to be made: depressive mood qualitatively different from the normal, worsening in the morning, terminal insomnia (to wake up at least two hours before the usual time), psychomotor retardation or agitation, anorexia or significant weight loss (5% of the body weight per month), excessive or inappropriate guilt. Sometimes, however, the depressive disorder is atypical with mood reactivity, i.e., enhancement of the mood in response to real or potential positive events, significant weight gain, increase in appetite, hypersomnia, sensation of heaviness in the upper and lower limbs, in addition to a prolonged pattern of sensitivity to interpersonal rejection resulting in significant social or occupational impairment . The dysthymic disorder (dysthymia) is characterized by a chronically depressed mood lasting for most of the day, for the majority of days, and lasting for at least two years . The individual may note significant reduction in usual interests and in self-criticism, frequently seeing himself or herself as uninteresting and incapable. As these symptoms become part of daily life, usually they are not mentioned by the patient unless directly inquired about by Andre Luiz Langer Manica, Carolina Garcia Soares Leaes, Benicio Noronha Frey, Mario Francisco Juruena

[Mycoplasma pneumoniae pneumonia: clinical and radiological features]

OBJECTIVE: To alert about the great variability of clinical and radiological features of Mycoplasma pneumoniae pneumonia in pediatric patients. Although it has been referred as a prevalent entity in children, its diagnosis is, many times, retarded due to the lack of a pattern that can really be considered classic.METHODS: The authors present 5 cases of mycoplasma pneumonia in children. Diagnostic difficulties, clinical features, radiological findings and evolution after treatment are discussed. The cases have their significant peculiarities confronted with the findings of medical literature of the last two decades, obtained through a bibliographic research in Medline about the subject.RESULTS: All the patients were between 6 and 9 years old, characteristically the most prevalent age group for this infection. In none of the cases the possibility of mycoplasma infection was considered at first. Clinical hypothesis like sinusal aspirative pneumonia, tuberculosis, and asthma were initially considered, but later on discarded. Except for one, all the other patients referred previous treatment with antibiotics. The initial radiological findings were different among the cases: bronchopneumonic consolidations, pleural effusion, perihilar adenopathy with interstitial infiltrated, and atelectasic areas. After the institution of specific therapy, clinical and radiological evolution was favorable in all cases.CONCLUSIONS: Mycoplasma pneumoniae pneumonia has a great sort of clinical presentations. In the same way the complementary radiological investigation may also demonstrate different patterns of presentation. Due to its great variability, mycoplasma is not commonly considered as the first diagnosis, even though it is a prevalent disease at pediatric age. This may lead to a delay in the diagnosis and institution of an appropriate treatment.

Prevalence of High Platelet Reactivity in Aspirin-Treated Patients Referred for Coronary Angiography

BACKGROUND Aspirin (ASA) reduces adverse events in coronary artery disease (CAD) patients by inhibiting platelets. Some CAD patients have high platelet reactivity (HPR) despite ASA therapy and these individuals have increased risk of adverse events. OBJECTIVE The purpose of this study was to determine the prevalence of HPR in ASA-treated patients referred for coronary angiography and to assess whether the HPR correlates with the severity of CAD. METHODS This single center investigation enrolled 115 consecutive ASA-treated patients with stable CAD. ADP- and collagen-induced platelet reactivity were evaluated by light transmittance aggregometry (LTA). Patients with greater than 70% ADP- and collagen-induced aggregation were determined to have HPR and, in this group, ASA compliance was assessed by examining blood salicylate levels. Mean age was 60.9 years and average ASA dose was 164.2 mg. RESULTS Smoking and DM were present in 28.7% and 31.5% respectively. HPR was found in 14 patients (13%) however 7 of the 14 patients (50%) with HPR had low serum salicylate levels (< 2.0 µg/mL) suggesting medication noncompliance. Of the entire cohort, 6.5% of patients had HPR and detectable serum salicylate levels suggesting reduced ASA efficacy. HPR correlated with number and severity of coronary stenosis (p = 0.04). CONCLUSION In a general population of ASA-treated patients referred for coronary angiography, elevated platelet reactivity is prevalent (13%) with 50% related to noncompliance and 50% related to reduced aspirin efficacy.

Papel dos inibidores da glicoproteína IIb/IIIa na resolução do segmento ST em pacientes submetidos a angioplastia primária

INTRODUCTION: Combination of angioplasty PTCA and glycoprotein IIb/IIIa inhibitors (IGpIIb/IIIa) already had conflicting results in treatment of patients (pts) with ST-elevation segment myocardial infarction (STEMI). OBJECTIVE: Determine if IIb/ IIIa as an adjunctive therapy to the primary PTCA is associated with a better ST segment (STSR) resolution in the electrocardiogram (EKG). METHODS: Of 85 patients submitted to a primary PTCA between 2000-2002, 35 used IIb/IIIa as an adjunct therapy and 50 did not use the drug (control group). Baseline characteristics were compared, and clinical, electrocardiographic and angiographic variables were similar between the groups. Outcomes analyzed were STSRs of early (first 6 hours after PTCA) and late EKGs (12 to 40 hours), in-hospital major adverse clinical cardiovascular events (MACE) and serum enzimatic peak. Significance was set at p < 0.05. RESULTS: The IIb/IIIa group showed a trend to a better STSR in early EKGs (73% vs 62%, p = 0.08), not observed when compared late EKGs (72% vs 73%, p = ns). A significant difference was found when the STSR between early vs. late EKGs in the control group (62% vs 73%, p = 0.006), but not in in the IIb/ IIIa group. Diabetes, inferior AMI, onset of symptoms in less then 6 hours and IIb/IIIa were predictors to a complete STSR (p = 0.04; OR = 3.1; IC 95% = 1 to 10). No differences were observed in the presence of in-hospital MACE or enzymatic peak. CONCLUSION: IIb/IIIa as an adjunctive therapy to the primary PTCA in the treatment of STEMI is associated with a better STSR in early EKG, which may indicate that the drug accelerates myocardial reperfusion in these patients.