Early holocenic and historic mtDNA african signatures in the iberian peninsula: The andalusian region as a paradigm

Determining the timing, identity and direction of migrations in the Mediterranean Basin, the role of "migratory routes" in and among regions of Africa, Europe and Asia, and the effects of sex-specific behaviors of population movements have important implications for our understanding of the present human genetic diversity. A crucial component of the Mediterranean world is its westernmost region. Clear features of transcontinental ancient contacts between North African and Iberian populations surrounding the maritime region of Gibraltar Strait have been identified from archeological data. The attempt to discern origin and dates of migration between close geographically related regions has been a challenge in the field of uniparental-based population genetics. Mitochondrial DNA (mtDNA) studies have been focused on surveying the H1, H3 and V lineages when trying to ascertain north-south migrations, and U6 and L in the opposite direction, assuming that those lineages are good proxies for the ancestry of each side of the Mediterranean. To this end, in the present work we have screened entire mtDNA sequences belonging to U6, M1 and L haplogroups in Andalusians--from Huelva and Granada provinces--and Moroccan Berbers. We present here pioneer data and interpretations on the role of NW Africa and the Iberian Peninsula regarding the time of origin, number of founders and expansion directions of these specific markers. The estimated entrance of the North African U6 lineages into Iberia at 10 ky correlates well with other L African clades, indicating that U6 and some L lineages moved together from Africa to Iberia in the Early Holocene. Still, founder analysis highlights that the high sharing of lineages between North Africa and Iberia results from a complex process continued through time, impairing simplistic interpretations. In particular, our work supports the existence of an ancient, frequently denied, bridge connecting the Maghreb and Andalusia.

Study to determine the cardiovascular risk ofthe population of Guimarães/Vizela, includingthe prevalence of arterial stiffness and early vascular aging syndrome

Tese de Doutoramento em Medicina.

Pulse wave velocity distribution in a cohort study: from arterial stiffness to early vascular aging

BACKGROUND: By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population. METHOD: Pulse wave velocity (PWV) was measured in randomly sampled population dwellers aged 18-96 years from northern Portugal, and used as a marker of early vascular aging (EVA). Of the 3038 individuals enrolled, 2542 completed the evaluation. RESULTS: Mean PWV value for the entire population was 8.4?m/s (men: 8.6?m/s; women: 8.2?m/s; P??10?m/s). Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds of PWV above 10?m/s 10 years later than men. CONCLUSION: The population PWV values were higher than expected in a low cardiovascular risk area (Portugal). High prevalence rates of EVA and noteworthy large artery damage in young ages were found.

Methylation at the CpG island shore region upregulates Nr3c1 promoter activity after early-life stress

Early-life stress (ELS) induces long-lasting changes in gene expression conferring an increased risk for the development of stress-related mental disorders. Glucocorticoid receptors (GR) mediate the negative feedback actions of glucocorticoids (GC) in the paraventricular nucleus (PVN) of the hypothalamus and anterior pituitary and therefore play a key role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the endocrine response to stress. We here show that ELS programs the expression of the GR gene (Nr3c1) by site-specific hypermethylation at the CpG island (CGI) shore in hypothalamic neurons that produce corticotropin-releasing hormone (Crh), thus preventing Crh upregulation under conditions of chronic stress. CpGs mapping to the Nr3c1 CGI shore region are dynamically regulated by ELS and underpin methylation-sensitive control of this region's insulation-like function via Ying Yang 1 (YY1) binding. Our results provide new insight into how a genomic element integrates experience-dependent epigenetic programming of the composite proximal Nr3c1 promoter, and assigns an insulating role to the CGI shore.

Atuação dos enfermeiros na emergência pré-hospitalar em situações de paragem cárdio-respiratória

Dissertação de mestrado em Enfermagem da Pessoa em Situação Crítica

Transmyocardial laser revascularization. Early clinical experience

OBJECTIVE: To analyze the initial clinical experience of transmyocardial laser revascularization (TMLR) in patients with severe diffuse coronary artery disease. METHODS: Between February, 1998 and February, 1999, 20 patients were submitted to TMLR at the Heart Institute (InCor), University of São Paulo Medical School, Brazil, isolated or in association with conventional coronary artery bypass graft (CABG). All patients had severe diffuse coronary artery disease, with angina functional class III/IV (Canadian Cardiovascular Society score) unresponsive to medical therapy. Fourteen patients were submitted to TMLR as the sole therapy, whereas 6 underwent concomitant CABG. Fifty per cent of the patients had either been previously submitted to a CABG or to a percutaneous transluminal coronary angioplasty (PTCA). Mean age was 60 years, ranging from 45 to 74 years. RESULTS: All patients had three-vessel disease, with normal or mildly impaired left ventricular global function. Follow-up ranged from 1 to 13 months (mean 6.6 months), with no postoperative short or long term mortality. There was significant symptom improvement after the procedure, with 85% of the patients free of angina, and the remaining 15 % of the patients showing improvement in functional class, as well as in exercise tolerance. CONCLUSION: This novel technique can be considered a low risk alternative for a highly selected group of patients not suitable for conventional revascularization procedures.

Mitral restenosis in the early postoperative period of a patient with systemic lupus erythematosus

A forty eight year old woman, who had undergone mitral comissurotomy and subsequently developed early restenosis, presented with major comissural fusion and verrucous lesions on the cuspid edges of the mitral valve, with normal subvalvar apparatus. Patient did well for the first six months after surgery when she began to present dyspnea on light exertion. A clinical diagnosis of restenosis was made, which was confirmed by an echocardiogram and cardiac catheterization. She underwent surgery, and a stenotic mitral valve with verrucous lesions suggesting Libman-Sacks' endocarditis was found. Because the diagnosis of systemic lupus erythematosus (SLE) had not been confirmed at that time, a bovine pericardium bioprosthesis (FISICS-INCOR) was implanted. The patient did well in the late follow-up and is now in NYHA Class I .

Critical aortic stenosis in the neonate. Clinical assessment and surgical outcome in 18 patients

OBJECTIVE - To assess neonates with aortic stenosis with early decompensation operated upon. (LCO) (CHF). METHODS - A and retrospective study analyzing 6 neonates with LCO, group I (GI), and 12 neonates with CHF, group II (GII). Clinical radiographic, electrocardiographic and echocardiographic findings also provided comparative bases for the study, as did surgical and evolutional findings. RESULTS - The mean ages at hospitalization and surgery (p = 0.0031) were 14.3 and 14.8 days in GI and 35.4 and 42.8 days in GII, respectively. Cardiac murmurs were more intense in GII (p = 0.0220). The aortic ring was smaller in GI (8.0 ± 2.5mm) as compared to GII (11.4±1.4mm) (p = 0.2882). Ventricular function was reduced to 18±5.5% and 33.3±7.6% in GI and GII, respectively (p = 0.0162). Aortic atresia, however, was present only in 2 neonates in GI. Five of 6 patients in GI died but all patients in GII survived (p=0.0007). In the latter group, 84.6% of the patients were in functional class I (FC-I) in the long-term follow-up, with moderate residual lesions in 6 neonates, discrete residual lesions in 4, and reoperation in 2. CONCLUSION - Aortic stenosis is a severe anomaly of the neonate, whose immediate evolution depends on the pre-operative anatomic and functional findings, and the late evolution essentially depends on the anatomic features of the valve.

Percutaneous mitral valvotomy in patients eighteen years old and younger. Immediate and late results

OBJECTIVE - To analyze immediate and late results of percutaneous mitral valvotomy (PMV) in patients <= 18 year. METHODS - Between August '87 and July '97, 48 procedures were performed on 40 patients. The mean age was 15.6 years; 68.7% were females four of whom were pregnant. RESULTS - Success was obtained in 91.7% of the procedures. Immediate complications were severe mitral regurgitation (6.3%) and cardiac tamponade (2.0%). Late follow-up was obtained in 88.8% of the patients (mean value=43.2±33.9 months). NYHA functional class (FC) I or II was observed in 96.2% of the patients and restenosis developed in five patients, at a mean follow-up of 29.7±11.9 months. Three patients presented with severe mitral insufficiency and underwent surgery. Two patients died. CONCLUSION - PMV represents a valid therapeutic option in young patients. In these patients, maybe because of subclinical rheumatic activity, restenosis may have a higher incidence and occur at an earlier stage than in others persons.

Immediate and long term evolution of valve replacement in children less than 12 years old

OBJECTIVE: The aim of this work was the follow-up and evaluation of valve replacement in children under 12 years of age. METHODS: Forty-four children less than 12 years old were underwent valve replacement at INCOR-HCFMUSP between January 1986 and December 1992. Forty (91%) were rheumatic, 39 (88.7%) were in functional classes II or IV, 19 (43.2%) were operated upon on an emergency basis, and 6 (13.6%) had atrial fibrillation. Biological prostheses (BP) were employed in 26 patients (59.1%), and mechanical prostheses (MP) in 18 (40.9%). Mitral valves were replaced in 30 (68.7%), aortic valves in 8 (18.2%), a tricuspid valve in 1 (2.3%), and double (aortic and mitral) valves in 5 (11.4) of the patients. RESULTS: Hospital mortality was of 4.5% (2 cases). The mean follow-up period was 5.8 years. Re-operations occurred in 63.3% of the patients with BP and in 12.5% of those with MP (p=0.002). Infectious endocarditis was present in 26.3% of the BP, but in none of the cases of MP (p=0.049). Thrombosis occurred in 2 (12.5%) and hemorrhage in one (6.5%) of the patients with a MP. Delayed mortality occurred in 5 (11.9%) of the patients over a mean period of 2.6 years; four had had BP and one had a MP (NS). Actuarial survival and re-operation-free curves after 10 years were respectively, 82.5±7.7 (SD)% and 20.6±15.9%. CONCLUSION: Patients with MP required fewer re-operation, had less infectious endocarditis and lower late mortality rates compared with patients with bioprostheses. The former, therefore, appear to be the best valve replacement for pediatric patients.

Myocardial revascularization with coronary endarterectomy. Stratification of risk factors for early mortality

OBJECTIVE: To determine the risk factors for mortality related to myocardial revascularization when performed in association with coronary endarterectomy. METHODS: We assessed retrospectively 353 patients who underwent 373 coronary endarterectomies between January '89 and November '98, representing 3.73% of the myocardial revascularizations in this period of time. The arteries involved were as follows: right coronary artery in 218 patients (58.45%); left anterior descending in 102 patients (27.35%); circumflex artery in 39 patients (10.46%); and diagonal artery in 14 patients (3.74%). We used 320 (85.79%) venous grafts and 53 (14.21%) arterial grafts. RESULTS: In-hospital mortality among our patients was 9.3% as compared with 5.7% in patients with myocardial revascularizations without endarterectomy (p=0.003). Cause of death was related to acute myocardial infarction in 18 (54.55%) patients. The most significant risk factors for mortality identified were as follows: diabetes mellitus (p=0.001; odds ratio =7.168), left main disease (<0.001; 9.283), female sex (0.01; 3.111), acute myocardial infarction (0.02; 3.546), ejection fraction <35% (<0.001; 5.89), and previous myocardial revascularization (<0.001; 4.295). CONCLUSION: Coronary endarterectomy is related to higher mortality, and the risk factors involved are important elements of a poor outcome.

Outcome of acute renal failure associated with cardiac surgery in infants

OBJECTIVE: To analyze the impact of acute renal failure (ARF) on the evolution of infants undergoing cardiac surgery. METHODS: We assessed 15 infants undergoing cardiac surgery who developed (ARF). Their demographic, clinical and surgical data, and evolution were analyzed. RESULTS: Their mean age was 4.4±4.0 months (8 days to 24 months). Twelve infants were males, and 4 patients already had ARF at surgery. The primary cause of ARF was immediate acute cardiac dysfunction in 10 infants, cardiac dysfunction associated with sepsis in 2 infants, and isolated sepsis in 3 infants. All children depended on mechanical ventilation during their postoperative period, 14 infants used vasoactive drugs, and 11 had an infectious process associated with ARF. Thirteen infants required dialytic treatment. Eleven infants developed oluguric ARF, and all had to undergo peritoneal dialysis; of the 4 patients with non-oliguric, 2 required dialysis, the main indication being hypervolemia. Of these 13 dialyzed infants, 4 died in the first 24 hours because of the severity of the underlying cardiac disease (mean urea level of 49±20 mg/dl). The mortality rate for the entire group was 60% , and it was higher among the patients with oliguria ARF (73% vs 25%, p<0.001). The cause of death was acute cardiac dysfunction in 6 infants (early type-1ARF) and sepsis in the 3 remaining infants (late type-2 ARF). CONCLUSION: The mortality rate of ARF associated with cardiac surgery in infants was hight, being higher among children with oliguria; peritoneal dialysis was indicated due to clinically uncontrolled hypervolemia and not to the uremic hypercatabolic state.

Coronary stent implantation in diabetic versus nondiabetic patients. Early and late outcomes

OBJECTIVE: To assess whether coronary stenting in diabetic patients provides in-hospital results and clinical evolution similar to those in nondiabetic patients. METHODS: From July `97 to April '99 we performed coronary stent implantation in 386 patients with coronary heart disease, who were divided into two groups: diabetic patients and nondiabetic patients. The in-hospital results and the clinical evolution of each group were retrospectively analyzed. RESULTS: The nondiabetic group comprised 305 (79%) patients and the diabetic group 81 (21%) patients. Basic clinical and angiographic characteristics were similar. Angiographic success was in diabetics = 96.6% vs in nondiabetics = 97.9% (p=ns). Among the major complications in the in-hospital phase, the rate of myocardial infarction was higher in the diabetic group (7.4% vs 1.9%) (p=0.022). In the follow-up, a favorable and homogeneous evolution occurred in regard to asymptomatic patients, myocardial infarction, and death in the groups. A greater need for revascularization, however, existed in the diabetic patients (15% vs 2.4%, p<0.001). CONCLUSION: Coronary stenting in diabetic patients is an efficient procedure, with a high angiographic and clinical success rate similar to that in nondiabetic patients. Diabetic patients, however, had a higher incidence of in-hospital myocardial infarction and a greater need for additional myocardial revascularization.

Acute myocardial infarction in progressively elderly patients. A comparative analysis of immediate results in patients who underwent primary percutaneous coronary intervention

OBJECTIVE: Analysis of the in-hospital results, in progressively elderly patients who undergo primary percutaneous coronary intervention (PCI) in the first 24 hours of AMI. METHODS: The patients were divided into three different age groups (60/69, 70/79, and > or = 80 years) and were treated from 7/95 until 12/99. The primary success rate and the occurrence of major clinical events were analyzed at the end of the in-hospital phase. Coronary stent implantation and abciximab use were employed at the intervencionist discretion. RESULTS: We analyzed 201 patients with age ranging from 60 to 93 years, who underwent primary PCI. Patients with ages above 70 were more often female (p=.015). Those with ages above 80 were treated later with PCI (p=.054), and all of them presented with total occlusion of the infarct-related artery. Coronary stents were implanted in 30% of the patients. Procedural success was lower in > or = 80 year old patients (p=.022), and the death rate was higher in > or = 70 years olds (p=.019). Reinfarction and coronary bypass surgery were uncommon events. A trend occurred toward a higher combined incidence of major in-hospital events according to increased age (p=.064). CONCLUSION: Elderly patients ( > or = 70 years) presented with adverse clinical and angiographic profiles and patients > or = 80 years of age obtained reduced TIMI 3 flow success rates after primary PTCA, and those > or = 70 years had a higher death rate.