Expressão de Aterosclerose Sub-Clínica para Diferentes Factores de Risco Cardiovasculares em Populações Jovens

INTRODUCTION: Carotid intima-media thickness (cIMT) is considered an early marker for atherosclerosis, but there are few studies on the expression of this marker in younger populations. OBJECTIVES: To evaluate cIMT in younge patients (aged 30-50 years) and its expression according to cardiovascular risk factors. METHODS: We analyzed individuals admitted for an invasive cardiac procedure. Normal cIMT was defined as < 0.90 mm, thickened as 0.90-1.50 mm and atherosclerotic plaque as > 1.50 mm. Lipid profile, anthropometric parameters, fasting blood glucose and estimated GFR were also determined. RESULTS: A total of 106 patients were included (59% male), with a mean age of 43 +/- 5 years, 36% with hypertension, 22% smokers, 32% with known hyperlipidemia, 16% with diabetes, 39% under statin therapy and 40% with metabolic syndrome (AHA/NHLBI definition). Mean cIMT was 0.69 +/- 0.26 mm, and was normal in 74% of the patients, thickened in 20% and with atherosclerotic plaques in 6%. cIMT correlated directly with age (r = 0.26, p = 0.007), log fasting glucose (r = 0.21, p = 0.04), and log triglycerides (r = 0.24, p = 0.017), and tended to correlate with the number of components of metabolic syndrome (r = 0.17, p = 0.08). However, on multivariate analysis, only age remained as an independent predictor (r = 0.29, p = 0.005). Diabetic patients had greater cIMT (0.81 +/- 0.22 vs. 0.67 +/- 0.26 mm, p = 0.039) and there was a trend for greater cIMT in those with metabolic syndrome (0.75 +/- 0.29 vs. 0.66 +/- 0.23 mm, p = 0.09). There were no differences for the other risk factors, A higher number of risk factors in a single patient showed a trend for increased cIMT (p = 0.083) CONCLUSIONS: Age is the only independent determinant of cIMT in a young population. Diabetic patients have greater cIMT and a trend was seen in those with metabolic syndrome, possibly influenced by its relation with diabetes, one of the components of the metabolic syndrome.

Estudo Comparativo, Aleatorizado, em Dupla Ocultação, de Orlistat Versus Placebo, de Eficácia e Segurança, em Doentes Obesos com Hipercolesterolemia Ligeira a Moderada

INTRODUCTION: Obesity is a chronic disease and a serious health problem that leads to increased prevalence of diabetes, hypertension, dyslipidemia and gallbladder disease. OBJECTIVE: To evaluate the efficacy of orlistat for weight loss and improved lipid profile compared to placebo in obese patients with hypercholesterolemia, treated over a period of 6 months. METHODOLOGY: In a 6-month, multicenter (10 centers in Portugal), double-blind, parallel, placebo-controlled study, 166 patients, aged 18-65 years, body mass index (BMI) > or = 27 kg/m2, LDL cholesterol > 155 mg/dl, were randomized to a reduced calorie diet (600 kcal/day deficit) plus orlistat three times a day or placebo. Exclusion criteria included triglycerides > 400 mg/dl, severe cardiovascular disease, uncontrolled hypertension, type 1 or 2 diabetes under pharmacological treatment, and gastrointestinal or pancreatic disease. RESULTS: The mean difference in weight from baseline was 5.9% (5.6 kg) in the orlistat group vs. 2.3% (2.2 kg) in the placebo group. In the orlistat group 49% of patients achieved 5-10% weight loss and 8.8% achieved > 10%. The orlistat group showed a significant reduction in total and LDL cholesterol, with similar changes for HDL in both treatment groups. The frequency of gastrointestinal adverse events was slightly higher in the orlistat group than in the placebo group, leading to discontinuation in 7 patients. CONCLUSION: Treatment with orlistat plus a reduced calorie diet for 6 months achieved significant reductions in weight, BMI and lipid parameters.

Relação entre Hipotiroidismo Subclínico e Doença Coronária: um Estudo com Angiografia

INTRODUCTION: The definition of subclinical hypothyroidism (SH) is an asymptomatic state in which free thyroxine (T4) is normal and thyroid-stimulating hormone (TSH) levels are elevated. Its relationship with coronary disease is not clear and has been the subject of recent interest. Current evidence is conflicting and there is a lack of studies supported by coronary angiography. OBJECTIVE: To assess the relationship between SH and the presence and extent of coronary disease diagnosed by angiography. METHODS: We prospectively studied 354 consecutive patients referred for elective coronary angiography. Those with known thyroid disease, documented coronary disease or previous myocardial infarction were excluded. Fasting blood specimens were collected to measure thyroid hormones, lipid profile, high-sensitivity C-reactive protein, fibrinogen and NT-proBNP. Patients with SH were compared with those without to assess differences in clinical characteristics and biochemical and angiographic results. Significant coronary disease was defined as the presence of at least one lesion with > or = 50% luminal stenosis. Lesions with <50% stenosis were considered minimal. RESULTS: SH was diagnosed in 32 (9%) patients. Mean age was similar between the groups. There were more women (66% vs. 39%; p=0.003) and atrial fibrillation was more frequent (25% vs. 11%; p=0.016) in the group of patients with SH. There were no significant differences in the other baseline clinical parameters, and blood biochemistry results were similar in the two groups, with the exception of higher levels of NT-proBNP in SH patients, although without statistical significance. The angiographic results were as follows: significant coronary disease (SH 28.1% vs. non-SH 43.8%; p=0.087); three-vessel disease (9.4% vs. 9.9%; p=0.919); two-vessel disease (12.5% vs. 13.4%; p=0.892); single-vessel disease (6.3% vs. 29.5%; p=0.051); minimal lesions (9.4% vs. 10.9%; p=0.794); and no coronary disease (62.4% vs, 45.3%; p=0.064). CONCLUSION: In this population SH was not associated with the presence or extent of coronary disease diagnosed by coronary angiography.

Impacto da Idade no Tratamento e Resultados Após Enfarte Agudo do Miocárdio em Particular nos Muito Idosos

INTRODUCTION: The elderly population admitted for acute myocardial infarction is increasing. This group is not well studied in international trials and is probably treated with a more conservative approach. OBJECTIVES: To evaluate the presentation and treatment of myocardial infarction according to age, particularly in very elderly patients. METHODS: We studied 1242 consecutive patients admitted with acute myocardial infarction, assessing in-hospital, 30-day and one-year mortality during follow-up for each age-group. Patients were divided into four groups according to age: <45 years (7.6%); 45-64 years (43.3%); 65-74 years (23.4%); and ≥75 years (25.7%). RESULTS: Elderly patients had a worse risk profile (except for smoking), more previous history of coronary disease and a worse profile on admission, with the exception of lipid profile, which was more favorable. With regard to treatment of the elderly, although less optimized than in other age-groups, it was significantly better compared to other registries, including for percutaneous coronary angioplasty. Both complications and mortality were worse in the older groups. In elderly patients (≥75 years), adjusted risk of mortality was 4.9-6.3 times higher (p<0.001) than patients in the reference age-group (45-64 years). In these patients, the independent predictors of death were left ventricular function and renal function, use of beta-blockers being a predictor of survival. CONCLUSIONS: Elderly patients represent a substantial proportion of the population admitted with myocardial infarction, and receive less evidenced-based therapy. Age is an independent predictor of short- and medium-term mortality.

Genomic Signatures and Antiviral Drug Susceptibility Profile of A(H1N1)pdm09

Background: Genetic changes in influenza surface and internal genes can alter viral fitness and virulence. Mutation trend analysis and antiviral drug susceptibility profiling of A(H1N1)pdm09 viruses is essential for risk assessment of emergent strains and disease management. Objective: To profile genomic signatures and antiviral drug resistance of A(H1N1)pdm09 viruses and to discuss the potential role of mutated residues in human host adaptation and virulence. Study design: A(H1N1)pdm09 viruses circulating in Portugal during pandemic and post-pandemic periods and 2009/2010 season. Viruses were isolated in MDCK-SIAT1 cell culture and subjected to mutation analysis of surface and internal proteins, and to antiviral drug susceptibility profiling. Results: The A(H1N1)pdm09 strains circulating during the epidemic period in Portugal were resistant to amantadine. The majority of the strains were found to be susceptible to oseltamivir and zanamivir, with five outliers to neuraminidase inhibitors (NAIs) identified. Specific mutation patterns were detected within the functional domains of internal proteins PB2, PB1, PA, NP, NS1, M1 and NS2/NEP, which were common to all isolates and also some cluster-specific. Discussion: Modification of viral genome transcription, replication and apoptosis kinetics, changes in antigenicity and antiviral drug susceptibility are known determinants of virulence. We report several point mutations with putative roles in viral fitness and virulence, and discuss their potential to result in more virulent phenotypes. Monitoring of specific mutations and genetic patterns in influenza viral genes is essential for risk assessing emergent strains, disease epidemiology and public health implications.

Validating Regulatory Sensory Processing Disorders Using the Sensory Profile and Child Behavior Checklist (CBCL 1 –5)

The objective was to validate Regulatory Sensory Processing Disorders’ criteria (DC:0-3R, 2005) using empirical data on the presence and severity of sensory modulation deficits and specific psychiatric symptoms in clinical samples. Sixty toddlers who attended a child mental health unit were diagnosed by a clinical team. The following two groups were created: toddlers with RSPD(N = 14) and those with ‘‘other diagnoses in Axis I/II of the DC:0-3R00(OD3R) (N = 46). Independently of the clinical process, parents completed the Infant Toddler Sensory Profile (as a checklist for sensory symptoms) and the Achenbach Behavior Checklist for ages 1/2–5 (CBCL 1/2–5). The scores from the two groups were compared. The results showed the following for the RSPD group: a higher number of affected sensory areas and patterns than in the OD3R group; a higher percentage of sensory deficits in specific sensory categories; and a higher severity of behavioral symptoms such as withdrawal, inattention, other externalizing problems and pervasive developmental problems in CBCL 1/2–5. The results confirmed our hypotheses by indicating a higher severity of sensory symptoms and identifying specific behavioral problems in children with RSPD. The results revealed convergent validity between the instruments and the diagnostic criteria for RSPD and supported the validity of RSPD as a unique diagnosis. The findings also suggested the importance of identifying sensory modulation deficits in order to develop an early intervention to enhance the sensory capacities of children who do not fully satisfy the criteria for some DSM-IV-TR disorders.

The Impact of the Lisbon Football Derby on the Profile of Emergency Department Admissions

BACKGROUND: Variations in emergency department admissions have been reported to happen as a result of major sports events. The work presented assessed changes in volume and urgency level of visits to a major Emergency Department in Lisbon during and after the city's football derby. MATERIAL AND METHODS: Volume of attendances and patient urgency level, according to the Manchester Triage System, were retrospectively analyzed for the 2008-2011 period. Data regarding 24-hour periods starting 45 minutes before kick-off was collected, along with data from similar periods on the corresponding weekdays in the previous years, to be used as controls. Data samples were organized according to time frame (during and after the match), urgency level, and paired accordingly. RESULTS: A total of 14 relevant periods (7 match and 7 non-match) were analyzed, corresponding to a total of 5861 admissions. During the match time frame, a 20.6% reduction (p = 0.06) in the total number of attendances was found when compared to non-match days. MTS urgency level sub-analysis only showed a statistically significant reduction (26.5%; p = 0.05) in less urgent admissions (triage levels green-blue). Compared to controls, post-match time frames showed a global increase in admissions (5.6%; p = 0.45), significant only when considering less urgent ones (18.9%; p = 0.05). DISCUSSION: A decrease in the total number of emergency department attendances occurred during the matches, followed by a subsequent increase in the following hours. These variations only reached significance among visits triaged green-blue. CONCLUSION: During major sports events an overall decrease in emergency department admissions seems to take place, especially due to a drop in visits associated with less severe conditions.

Clinical Outcomes and Genetic Expression Profile in Human Liver Graft Dysfunction During Ischemia/Reperfusion Injury

Introduction. This study aims to compare the molecular gene expression during ischemia reperfusion injury. Several surgical times were considered: in the beginning of the harvesting (T0), at the end of the cold ischemia period (T1), and after reperfusion (T2) and compared with graft dysfunction after liver transplant (OLT). Methods. We studied 54 patients undergoing OLT. Clinical, laboratory data, and histologic data (Suzuki classification) as well as the Survival Outcomes Following Liver Transplantation (SOFT) score were used and compared with the molecular gene expression of the following genes: Interleukin (IL)-1b, IL-6, tumor necrosis factor-a, perforin, E-selectin (SELE), Fas-ligand, granzyme B, heme oxygenase-1, and nitric oxide synthetase. Results. Fifteen patients presented with graft dysfunction according to SOFT criteria. No relevant data were obtained by comparing the variables graft dysfunction and histologic variables. We observed a statistically significant relation between SELE at T0 (P ¼ .013) and IL-1b at T0 (P ¼ .028) and early graft dysfunction. Conclusions. We conclude that several genetically determined proinflammatory expressions may play a critical role in the development of graft dysfunction after OLT.

Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug Reactions

OBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.

Different in Vivo Reactivity Profile in Health Care Workers and Patients with Spina Bifida to Internal and External Latex Glove Surface-Derived Allergen Extracts

BACKGROUND: Allergy to natural rubber latex is a well-recognized health problem, especially among health care workers and patients with spina bifida. Despite latex sensitization being acquired in health institutions in both health care workers and patients with spina bifida, differences in allergen sensitization profiles have been described between these two risk groups. OBJECTIVE: To investigate the in vivo reactivity of health care workers and patients with spina bifida to extracts of internal and external surfaces of latex gloves and also to specific extracts enriched in major allergens for these risk groups. METHODS: Gloves from different manufacturers were used for protein extraction, and salt precipitation and hydrophobic interaction chromatography (HIC) were applied to obtain the enriched latex extracts. The major latex allergens were quantified by an enzyme immunoassay. The extracts obtained were tested in 14 volunteers using skin prick tests (SPT). RESULTS: Latex glove extracts enriched in the hydrophobic allergens that are most often seen in patients with spina bifida were obtained by selective precipitation, whereas HIC produced extracts enriched in the hydrophilic allergens commonly found in health care workers. The health care workers had positive SPTs to glove extracts from internal surfaces and to the hydrophilic allergen-enriched extracts. By contrast, patients with spina bifida had larger skin reactions both to external glove extracts and to the extracts enriched with the hydrophobic major allergens for this risk group. Despite the protein concentration of these extracts being less than half the concentration of the commercial extract, the weal-and-flare reactions were of similar magnitude. CONCLUSION: Using novel latex extracts, our study showed a different in vivo reactivity pattern in health care workers and in patients with spina bifida to extracts of the internal and external surfaces of gloves, which suggests that sensitization may occur by different routes of exposure, and that this influences the allergen reactivity profiles of these risk groups