The Beneficial Effects of Prenatal Biotin Supplementation in a Rat Model of Intrauterine Caloric Restriction to Prevent Cardiometabolic Risk in Adult Female Offspring.

Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee's index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee's index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits.

Knowledge and Practices of Pediatricians Regarding Functional Constipation in the State of Minas Gerais, Brazil.

OBJECTIVES: The aim of the study was to analyze the knowledge, approaches, and practices of pediatricians participating in a regional pediatric conference regarding functional constipation (FC) to identify knowledge gaps. METHODS: Cross-sectional regional study based on a semistructured questionnaire related to the Rome III criteria and the participant profiles. RESULTS: Of 400 questionnaires distributed, 264 (66.0%) were completed. Most pediatricians (76.7%) did not recognize the Rome III criteria, but the majority did recognize the following risk factors for FC: low-fiber diet (97.8%), family history (86.6%), onset of toilet training (76.4%), and weaning (62.4%). Foods considered high in fiber were oats (95.7%), leafy vegetables (95.3%), and wheat bran (93.2%). Digital rectal examination was not performed by 57.7% of nongastroenterologists. Complementary examinations were ordered in 27.5% and 72.5% of patients by general pediatricians and pediatric gastroenterologists, respectively, although the sample of gastroenterologists was not representative. The most prescribed drugs by nongastroenterologists were mineral oil (72.6%), magnesium hydroxide (52.1%), lactulose (41.0%), and polyethylene glycol (25.2%). Pediatric gastroenterologists prescribed magnesium hydroxide (91.7%), polyethylene glycol (91.7%), and mineral oil (58.3%). Most pediatricians (70.0%) considered the average treatment duration to be less than 1 year, although gastroenterologists considered it to be more than 1 year (54.6%). CONCLUSIONS: The knowledge of pediatricians regarding FC is inadequate. Constipation may not receive the public health attention it deserves within pediatric residency programs. The authors suggest that better education regarding FC should be included in medical school and residency program curricula to improve patient care.

Chronic functional constipation in children: adherence and factors associated with drug treatment.

OBJECTIVE: The aim of the present study was to evaluate the treatment adherence of children with chronic functional constipation. METHODS: The present study is a prospective and longitudinal study realized at a pediatric gastroenterology clinic of a Brazilian University Hospital, between August 2009 and October 2011. Rome III criteria and the Bristol Stool Scale were used to define constipation and to characterize feces, respectively. Drug treatment was prescribed for patients according to the protocols previously standardized in the clinic. Specific questionnaires, containing questions related to 1 dependent variable and independent variables were completed in the first and sixth months of the treatment. Independent variables related to the patients, their caregivers, the disease itself, and the therapeutic plan were analyzed and compared with the dependent variable (adherence to the treatment). Adherence was considered when the patient returned with >75% of the prescribed medicine containers empty. RESULTS: Fifty children participated in both the first and sixth months of treatment. The mean age of the sample was 77.6 ± 43.8 months and the mean age of the onset of symptoms was 18.8 ± 27.9 months. The adherence rate was 38% in the first month and 30% in the sixth month. Patients who were treated with polyethylene glycol had greater adherence than patients who were prescribed other laxatives, with statistical significance in the second moment of the study (P = 0.19 and P = 0.04, respectively). CONCLUSIONS: The study showed low adherence rates to drug treatment of constipation in children. It is necessary to seek new strategies to increase treatment adherence, while avoiding complications and reducing costs.

Combination of diacerhein and antiepileptic drugs after local peripheral, and oral administration in the rat formalin test.

Preclinical Research The present study was designed to evaluate the possible antinociceptive interaction between diacerhein and some antiepileptic drugs (carbamazepine, topiramate and gabapentin) on formalin-induced nociception. Diacerhein, each of the antiepileptics or a fixed dose-ratio combination of these drugs was assessed after local peripheral and oral administration in rats. lsobolographic analyses were used to define the interaction between drugs. Diacerhein, antiepileptic drugs (carbamazepine, topiramate and gabapentin) or their combinations yielded a dose-dependent antinociceptive effect when administered by both routes. Theoretical ED30 values for the combination estimated from the isobolograms were obtained as follows: diacerhein-carbamazepine (85.99 ± 7.07 µg/paw; 56.53 ± 4.56 mg/kg po), diacerhein-topiramate (197.97 ± 22.90 µg/paw; 13.06 ± 2.44 mg/kg po) and diacerhein-gabapentin (96.87 ± 17.73 µg/paw; 17.90 ± 4.70 mg/kg p.o.) for the local peripheral and oral administration routes, respectively. These values were significantly higher than the experimentally obtained ED30 values: diacerhein-carbamazepine (49.33 ± 3.37 µg/paw; 35.49 ± 7.91 mg/kg po), diacerhein-topiramate (133.00 ± 39.10 µg/paw; 8.87 ± 1.46 mg/kg po) and diacerhein-gabapentin (70.98 ± 14.73 µg/paw; 10.95 ± 3.23 mg/kg po). The combinations produced their antinociceptive effects without motor impairment in the rotarod test indicating synergistic interactions with a good side effect profile.

Dietary calcium intake is associated with adiposity, metabolic profile, inflammatory state and blood pressure, but not with erythrocyte intracellular calcium and endothelial function in healthy pre-menopausal women.

Recent studies have suggested that dietary Ca may have beneficial effects on adiposity, insulin resistance, dyslipidaemia and blood pressure (BP). One potential mechanism underlying these benefits involves modifications in intracellular Ca concentration ([Ca2+]i). The present study aimed to evaluate the associations of dietary Ca with adiposity, erythrocyte [Ca2+]i, metabolic profile, BP, inflammatory state and endothelial function in healthy pre-menopausal women. In the present cross-sectional study, seventy-six women aged 18­50 years were submitted to the evaluation of dietary intake, anthropometric parameters, body composition, erythrocyte [Ca2+]i, biochemical variables, endothelial function and BP. A FFQ was used to assess usual dietary intake. Endothelial function was evaluated by serum concentrations of adhesion molecules and by the peripheral arterial tonometry (PAT) method, using Endo-PAT 2000®. Participants were allocated into two groups according to Ca intake: low-Ca group (LCG; n 32; < 600 mg/d) and high-Ca group (HCG; n 44; ≥ 600 mg/d). Women in the LCG compared with those in the HCG exhibited, after adjustments for potential confounders, higher values of BMI, waist circumference, waist:height ratio, percentage of body fat, insulin, homeostasis model assessment of insulin resistance, leptin, diastolic and mean BP; and lower levels of HDL-cholesterol, adiponectin and vascular cell adhesion molecule 1. Endothelial function assessed by PAT and [Ca2+]i was similar in both groups. Subjects in the HCG had lower OR for prevalent overweight, obesity, abdominal obesity, insulin resistance, HDL-cholesterol < 600 mg/l and systolic BP >120 mmHg. The findings of the present study suggest that high Ca intake is inversely associated with some cardiovascular risk factors.

A pilot study on the relation between dietary calcium and clinical parameters in renal transplant recipients.

OBJECTIVE: This aim of this study was to evaluate the association between dietary calcium and variables that include body mass index, abdominal obesity, metabolic profile, and blood pressure levels in renal transplant patients. DESIGN: A cross-sectional study was conducted. SETTING: Eligible patients were recruited from renal transplant outpatient clinics at Pedro Ernesto University Hospital, Rio de Janeiro, Brazil. PATIENTS: A total of 40 men and 34 women aged >18 years who had received kidney transplants in the past ≥12 months were included in this study. INTERVENTION: All patients underwent clinical, dietary, anthropometric, and biochemical evaluation. RESULTS: Participants were classified into the following 2 groups on the basis of their mean dietary calcium intake: group A (<600 mg/day) and group B (≥600 mg/day). Patients in group B presented significantly lower levels of waist circumference and waist-to-hip ratio as compared with those in group A (P = .04 and P = .005, respectively), after adjusting for confounding variables such as energy intake, gender, age, physical activity, time since transplantation, and prednisone dose. After controlling for potential confounders, including energy intake and physical activity, subjects in group B had a lower odds ratio for prevalent abdominal obesity as compared with those in group A (odds ratio, 0.17; 95% confidence interval, 0.03 to 0.94; P = .04). Body mass index was significantly lower in patients with higher calcium intake; however, this difference did not reach statistical significance after adjustments for confounding factors. Metabolic profile and blood pressure levels were similar in both groups. CONCLUSION: The findings of the present study suggest that a higher dietary calcium intake may be associated with lower abdominal adiposity in renal transplant patients.

In vitro and in vivo antiproliferative activity of Calotropis procera stem extracts.

The cytotoxic potential of stem organic extracts from Calotropis procera (Asclepiadaceae) was firstly evaluated against cancer cell lines by MTT assay. Subsequently, samples considered cytotoxic were tested for antimitotic activity on sea urchin egg development and for in vivo antiproliferative activity in mice bearing Sarcoma 180 tumor. Among the five extracts (hexane, dichloromethane, ethyl acetate, acetone and methanol), ethyl acetate and acetone extracts displayed higher cytotoxic potential against tumor cells, with IC50 ranging from 0.8 to 4.4 microg/mL, while methanolic extract was weakly cytotoxic. Cytotoxic extracts also exhibited cell division inhibition capacity by antimitotic assay, revealing IC50 values lower than 5 microg/mL. In the in vivo antitumor assessments, ethyl acetate- and acetone-treated animals showed tumor growth inhibition ratios of 64.3 and 53.1%, respectively, with reversible toxic effects on liver and kidneys. Further studies are in progress in order to identify C. procera cytotoxic compound(s) and to understand the mechanism of action responsible for this tumor-decreasing potential.

Fabry disease caused by the GLA p.Phe113Leu (p.F113L) variant: Natural history in males.

BACKGROUND, AIMS AND METHODS: The α-galactosidase gene (GLA) c.337T>C/p.Phe113Leu variant was originally described in patients with late-onset cardiac forms of Fabry disease (FD), who had residual α-galactosidase activity. It has since emerged as the most commonly reported GLA variant in Portuguese subjects diagnosed with FD but is also prevalent in the Italian population, where two boys carrying the GLA Leu113 allele were identified in a large-scale newborn screening program, the variant allele segregating in both cases with the same surrounding haplotype. To further delineate the genotype-phenotype correlations of this GLA variant, we have reviewed the natural history and clinical phenotypes of 11 symptomatic Portuguese males, from 10 unrelated families originating from several different areas in mainland Portugal and Madeira Island, who were diagnosed with FD associated with the GLA Leu113 allele in a diversity of clinical and screening settings. Nine of the patients were the probands of their respective families. To test whether the GLA Leu113 allele inherited by the 10 Portuguese and the two Italian families resulted from independent mutational events, we have additionally performed a haplotype analysis with 5 highly polymorphic, closely linked microsatellite markers surrounding the GLA gene. RESULTS AND CONCLUSIONS: Hemizygosity for the GLA Leu113 variant allele is associated with a late-onset form of FD, invariably presenting with severe cardiac involvement. Clinically relevant cerebrovascular and kidney involvement may also occur in some patients but the pathogenic relationship between the incomplete α-galactosidase deficiency and the risks of stroke and of chronic kidney disease is not straightforward. The observation that the Leu113 allele segregated within the same GLA microsatellite haplotype in both the Portuguese and Italian families suggests its inheritance from a common ancestor.

Prognostic impact of hemoglobin drop during hospital stay in patients with acute coronary syndromes.

INTRODUCTION: Bleeding is currently the most common non-cardiac complication of therapy in patients with acute coronary syndromes (ACS), and may itself be associated with adverse outcomes. The aim of this study was to determine the effect of hemoglobin drop during hospital stay on outcome among patients with ACS. METHODS: Using Cox proportional-hazards modeling, we examined the association between hemoglobin drop and death or myocardial infarction (MI) at 6 months in 1172 patients admitted with ACS to an intensive cardiac care unit. Patients were stratified according to quartiles of hemoglobin drop: Q1, < or = 0.8 g/dL; Q2, 0.9-1.5 g/dL; Q3, 1.6-2.3 g/dL; Q4, > or = 2.4 g/dL. We also identified independent predictors of increased hemoglobin drop (> or =2.4 g/dL) using multivariate logistic regression analysis. RESULTS: Median nadir hemoglobin concentration was 1.5 g/dL lower (IQR 0.8-2.3) compared with baseline hemoglobin (p < 0.0001). Independent predictors of increased hemoglobin drop included older Sage, renal dysfunction, lower weight, and use of thrombolytic therapy, glycoprotein IIb/IIIa inhibitors, nitrates, and percutaneous coronary intervention. Higher levels of hemoglobin drop were associated with increased rates of 6-month mortality (8.0% vs. 9.4% vs. 9.6% vs. 15.7%; p for trend = 0.014) and 6-month death/ MI (12.4% vs. 17.0% vs. 17.2% vs. 22.1%; p for trend = 0.021). Using Q1 as reference group, the adjusted hazard ratio (HR) for 6-month mortality and 6-month death/MI among patients in the highest quartile of hemoglobin drop was 1.83 (95% confidence interval [CI] 1.08-3.11; p = 0.026) and 1.60 (95% CI 1.04-2.44; p = 0.031) respectively. Considered as a continuous variable, the adjusted HR for 6-month mortality was 1.16 (95% CI 1.01-1.32; p = 0.030) per 1 g/dL increase in hemoglobin drop. CONCLUSIONS: A decrease in hemoglobin frequently occurs during hospitalization for ACS and is independently associated with adverse outcomes.

Smoking in acute coronary syndromes--the "smoker's paradox" revisited.

INTRODUCTION: Although a well-known risk factor for coronary disease, smoking has long been associated with lower short-term mortality in acute coronary syndromes (ACS). There are few recent works on Portuguese populations examining all aspects of smoking in ACS, particularly the interaction between smoking and other risk factors, and the management and prognosis of patients according to smoking status. OBJECTIVE: We sought to examine clinical characteristics, presentation, in-hospital treatment, angiographic features and prognosis of patients with and without smoking history admitted with ACS. METHODS: A total of 1228 patients consecutively admitted with ACS from January 2004 to March 2007 were analyzed. Patients were classified into two groups, those with present or past smoking habits (n=450) making up Group I and those without smoking habits (n=778), Group II. The main outcome analyzed was overall mortality during hospital stay and at 6 months. RESULTS: Smokers and former smokers were younger and more frequently male (odds ratio [OR] = 22.46; 95% confidence interval [CI]: 12.94-38.96), and less often had diabetes (OR = 0.41; 95% CI: 0.30-0.54), hypertension (OR = 0.31; 95% CI: 0.24-0.39) and renal insufficiency (OR = 0.26; 95% CI: 0.18-0.36). Patients with smoking habits more frequently presented with ST elevation (OR = 1.32; 95% CI: 1.04-1.67), more often received evidence-based medical therapy, namely beta blockers (during hospital stay, OR = 2.42; 95% CI: 1.63-3.56 and at discharge, OR = 1.45; 95% CI: 1.03-2.1) and statins (at discharge, OR = 2.48; 95% CI: 1.2-6.1), and more frequently underwent coronary angiography (OR = 2.15; 95% CI: 1.63-2.84). Although smokers and former smokers had lower in-hospital mortality on univariate analysis (OR = 0.54; 95% CI: 0.31-0.96), this association was not confirmed on multivariate analysis, with adjustment for known short-term mortality predictors (OR = 1.25; 95% CI: 0.61-2.54). Similarly, multivariate analysis failed to confirm lower 6-month mortality for smokers and former smokers (OR = 2.0; 95% CI: 1.17-3.41). CONCLUSIONS: Clinical characteristics and management options differed between ACS patients with and without smoking habits. These differences explained the lower shortterm mortality initially observed between the two groups. In our population of patients admitted with ACS, we did not find a real "smoker's paradox".

Non-ST elevation acute coronary syndrome: QRS duration and long-term prognosis.

BACKGROUND: Recent studies have demonstrated that QRS duration (QRSd) is associated with poor prognosis in heart failure and ST-elevation myocardial infarction. Less is known about the prognostic importance of QRSd in patients with non-ST elevation acute coronary syndrome (non-ST ACS). AIM: To determine if admission QRSd is associated with 1-year mortality in non-ST ACS. METHODS: We studied 539 patients (aged 65.52 +/- 12.47 years, 69.9% male) admitted to the coronary unit with non-ST ACS. QRSd was measured on the admission electrocardiogram. RESULTS: Mean QRSd was 94.29 +/- 18.3 ms. One-year mortality was 13.4%. QRSd showed a good correlation with 1-year mortality and its best cut-off was 92 ms. Patients with QRSd > or = 92 ms were older, more frequently male and with prior history of coronary heart disease. On admission they presented more often in Killip class > 1, and had a higher incidence of heart failure and left ventricular systolic dysfunction. They less often underwent coronary angiography. One-year mortality was higher in patients with QRSd > or = 92 ms. After adjusting for baseline characteristics and treatment, QRSd > or = 92 ms remained an independent predictor of 1-year mortality (adjusted OR=3.87; 95% CI 1.74-8.44). CONCLUSION: In this non-ST ACS population, QRSd was an independent predictor of 1-year mortality after the event.

Prognostic impact of moderate renal dysfunction in acute coronary syndromes.

INTRODUCTION: End-stage renal disease is associated with high cardiovascular mortality. The prognostic importance of milder degrees of renal impairment in patients who have had an acute coronary syndrome (ACS) is less well defined. The purpose of this study was to evaluate the impact of baseline renal dysfunction assessed by estimated glomerular filtration rate (GFR) on mortality in patients admitted with an ACS. METHODS: We studied all patients with an ACS consecutively admitted to an Intensive Cardiac Care Unit over 18 months. The GFR was estimated by means of the four-component Modification of Diet in Renal Disease study equation. Patients were grouped according to their estimated GFR (less than 45.0; 45.0 to 59.9; 60.0 to 74.9; and at least 75.0 ml/min/1.73 m2). Primary outcome was death from any cause. RESULTS: The mean age of the 589 study patients was 64.1 years, 73.7% were male, and 49.2% had an ACS with ST-segment elevation. Arterial hypertension, diabetes mellitus, prior myocardial infarction, and Killip class > I were incrementally more common across increasing renal dysfunction strata (p < 0.01). The use of reperfusion therapy, beta-blockers, and coronary angioplasty was lower in groups with reduced estimated GFR (p < 0.001). Overall six-month mortality was 13.6%. Using the group with an estimated GFR of at least 75.0 ml/min/1.73 m2 as the reference group yielded odds ratios for six-month mortality that increased with the degree of renal impairment. After adjusting for baseline characteristics, impaired renal funtion remained associated with increased mortality. The multivariable-adjusted odds ratio for six-month mortality in patients with mild renal impairment (GFR 60.0 to 74.9 ml/min/1.73 m2) was 2.71 (95% confidence interval [CI] 1.09 to 6.69), compared with 7.53 (95% CI, 3.21 to 17.71) and 8.10 (95% CI, 3.18 to 20.60) in patients with moderate and more severe renal dysfunction, respectively. CONCLUSIONS: Baseline renal dysfunction, as assessed by estimated GFR, is a potent and easily identifiable determinant of outcome after an ACS. Even mild levels of renal impairment are independently associated with increased mortality after an ACS.

Impact of atrial fibrillation in acute coronary syndromes.

INTRODUCTION: Atrial fibrillation (AF) is a relatively common arrhythmia in the context of acute coronary syndromes (ACS). However, the impact of AF on these patients' survival is not well established. The present study aimed to estimate the prevalence of AF in ACS patients and to evaluate its impact on in-hospital and six-month post-event mortality, from any cause. METHODS: This was a retrospective cohort study that included 1183 patients admitted consecutively to a Coronary Care Unit with ACS. Demographic and clinical data and information from various complementary exams were collected and occurrence of AF during the first 48 hours of hospitalization was analyzed. Six-month follow-up was achieved in 95.9% of the patients. Logistic regression statistical analysis was used to identify independent predictors of in-hospital and six-month post-event mortality. RESULTS: AF was diagnosed in 140 patients (11.8%); these patients were older (73.89 +/- 8.69 vs. 63.20 +/- 12.73 years; p<0.0001) and less likely to be male (60.0% vs. 74.1%; p=0.001), and had a lower prevalence of dyslipidemia (32.9% vs. 44.1%; p=0.001) and smoking (10.0% vs. 25.9%; p<0.0001). Fewer patients with AF underwent reperfusion therapy (19.3% vs. 29.7%; p=0.006), beta-blocker therapy (72.1% vs. 85.7%; p<0.0001), and cardiac catheterization (48.2% vs. 62.9%; p=0.001) or percutaneous coronary intervention (14.3% vs. 23.4%; p=0.01). These patients more frequently developed heart failure (54.3% vs. 28.5%; p<0.0001) and more often presented left ventricular dysfunction (69.3% vs. 57.2%; p=0.002). In patients presenting AF, there were significant increases in in-hospital (12.1% vs. 4.2%; p<0.0001) and six-month mortality (27.2% vs. 8.2%. p<0.0001). In multivariate analysis, AF remained an independent marker of in-hospital (OR 1.95; 95% CI 1.03-3.69; p=0.03) and six-month mortality (OR 2.89; 95% CI 1.67-5.00; p=0.0001), as was age >75 years, severe left ventricular dysfunction and heart failure. The performance of coronary angiography correlated with improved prognosis. CONCLUSIONS: AF in the context of ACS is an independent predictor of increased in-hospital and six-month mortality. These findings should be taken into consideration in the management and treatment of such patients.

Extraction and physicochemical characterization of Sargassum vulgare alginate from Brazil.

Alginate fractions from Sargassum vulgare brown seaweed were characterized by (1)H NMR and fluorescence spectroscopy and by rheological measurements. The alginate extraction conditions were investigated. In order to carry out the structural and physicochemical characterization, samples extracted for 1 and 5h at 60 degrees C were further purified by re-precipitation with ethanol and denoted as SVLV (S. vulgare low viscosity) and SVHV (S. vulgare high viscosity), respectively. The M/G ratio values for SVLV and SVHV were 1.56 and 1.27, respectively, higher than the ratio for most Sargassum spp. alginates (0.19-0.82). The homopolymeric blocks F(GG) and F(MM) of these fractions characterized by (1)H NMR spectroscopy were 0.43 and 0.55 for SVHV and 0.36 and 0.58 for SVLV samples, respectively, these values typically being within 0.28-0.77 and 0.07-0.41, respectively. Therefore, the alginate samples from S. vulgare are much richer in mannuronic block structures than those from other Sargassum species. Values of M(w) for alginate samples were also calculated using intrinsic viscosity data. The M(w) value for SVLV (1.94 x 10(5)g/mol) was lower than that for SVHV (3.3 x 10(5)g/mol). Newtonian behavior was observed for a solution concentration as high as 0.7% for SVLV, while for SVHV the solutions behaved as a Newtonian fluid up to 0.5%. The optimal conditions for obtaining the alginates from S. vulgare were 60 degrees C and 5h extraction. Under these conditions, a more viscous alginate in higher yield was extracted from the seaweed biomass.

Cardiovascular toxicity of cocaine of iatrogenic origin. Case report.

The use of cocaine as an illicit drug is associated with various cardiovascular events. In recent decades, because of growing levels of consumption, there has been an increasing incidence of these complications. At the same time, cocaine is also widely used as a local anesthetic, mainly in nasal surgery. Its application in this context is controversial due to the potential associated adverse effects. The authors report the case of a 29-year-old patient, with no known cardiovascular risk factors, admitted for elective nasal surgery, under general anesthesia combined with topical application of cocaine. During surgery the patient developed hemodynamic instability in the context of ventricular arrhythmias, after which she presented evolving electrocardiographic changes and increased levels of myocardial necrosis markers, diagnostic of non-ST-segment elevation acute coronary syndrome. The authors review the cardiovascular complications associated with cocaine use and the underlying pathophysiologic mechanisms and discuss the role of cocaine as a topical anesthetic.

Admission glycemia: a predictor of death after acute coronary syndrome in non-diabetic patients?

BACKGROUND: Previous studies have demonstrated that acute phase hyperglycemia is associated with increased in-hospital mortality in diabetic patients admitted with acute coronary syndrome (ACS), but this has not been clearly demonstrated in non-diabetic patients. The present study was designed to determine whether admission hyperglycemia (AG) is an independent predictor of in-hospital and six-month mortality after ACS in non-diabetic patients. METHODS: This was a retrospective cohort study of 426 non-diabetic patients consecutively admitted with ACS. The patients were stratified into quartile groups according to AG, which was also analyzed as a continuous variable. Vital status was obtained at six-month follow-up in 96.8% of the patients surviving hospitalization. Logistic regression analysis was used to identify independent predictors of in-hospital and six-month death. RESULTS: Of the 426 patients included in the study (age 62.6 years+/-13.1, 77% male), 22 (5.4%) patients died during hospitalization and 20 (5.2% of the patients surviving hospitalization) within six months of ACS. Mean AG was 134.89 mg/dl+/-51.95. The higher the AG, the more probable was presentation with ST-segment elevation ACS (STEMI), anterior STEMI, higher heart rate, Killip class higher than one (KK >1), higher serum creatinine and greater risk of in-hospital and six-month death. In multivariate analysis, only age (OR=1.10; 95% CI 1.04-1.17), STEMI (OR=3.02; 95% CI 1.07-8.50), AG (OR=1.073; 95% CI 1.004-1.146), serum creatinine (OR=1.10; 95% CI 1.009-1.204) and KK >1 on admission (OR=4.65; 95% CI 1.59-13.52) were independently associated with in-hospital death. Age (OR=1.07; 95% CI 1.03-1.12), serum creatinine (OR=1.09; 95% CI 1.01-1.18) and in-hospital development of heart failure (OR=2.34; 95% CI 1.07-5.10) were independently associated with higher risk of death within six months of ACS. CONCLUSIONS: AG is an independent predictive factor of in-hospital death after ACS in non-diabetic patients. Although it did not show an independent association with higher risk of six-month death, AG appears to contribute to it, since the risk is greater the higher the AG. Its predictive value may have been blunted by the insufficient power of the sample and/or by the time interval between acquisition of AG and the evaluated endpoint.

Heart failure after acute coronary syndrome: identify to treat better!

INTRODUCTION: The development of heart failure (HF) following acute coronary syndromes (ACS) significantly worsens short- and long-term prognosis. The present study aimed to identify clinical characteristics, detectable at admission for ACS, that could predict HF development during hospitalization, and to evaluate its impact on in-hospital mortality. METHODS: This was a retrospective cohort study that included 601 patients consecutively admitted with ACS. Demographic, clinical and laboratory data at admission were collected and HF was defined as maximum Killip class II or III. Logistic regression analysis was performed to identify independent predictors of HF and, additionally, in-hospital death. RESULTS: 29.3% of the population developed HF, mostly older patients (69.52+/-11.9 years vs. 61.81+/-12.4 years, p<0.0001), women, hypertensive, diabetic and non-smokers. On admission, this subgroup of patients presented with higher heart rate and glycemia, and lower glomerular filtration rate (eGFR) and hemoglobin. The percentage of patients with left ventricular systolic dysfunction (LVSD) was significantly higher in the group of patients with HF (74.4% versus 48.7%, p<0.0001); however, no significant differences were found in the type of ACS or its location. In the present study, we found that patients with HF were stratified less invasively (less likely to undergo cardiac catheterization or percutaneous coronary intervention). The development of HF was associated with longer hospitalization and higher in-hospital mortality (7.4% versus 2.1%, p=0.004) on univariate analysis, but not on multivariate analysis. On multivariate analysis, only age (OR=1.04; 95% CI 1.02-1.06), diabetes mellitus (OR=1.77; 95% CI 1.05-2.96), glycemia (OR=1.05; 95% CI 1.01-1.08), eGFR <60 ml/min/1.73m2 (OR=2.90, 95% CI 1.73- 4.84), heart rate (OR=1.03, 95% CI 1.02-1.04) and LVSD (OR=2.48, 95% CI 1.59-3.85) were independent predictors of HF. CONCLUSIONS: HF is a frequent complication in ACS and is associated with higher in-hospital mortality. Identifying risk of HF development on admission, through easily acquired clinical characteristics (older age, diabetes and/or elevated glycemia, renal failure and higher heart rate), will certainly influence immediate therapeutic choices and permit an individualized approach to each patient.

Biomarkers and Imaging Findings of Anderson-Fabry Disease-What We Know Now.

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The aim of this article is to review the current available literature on biomarkers and imaging findings of AFD patients. An extensive bibliographic review from PubMed, Medline and Clinical Key databases was performed by a group of experts from nephrology, neurology, genetics, cardiology and internal medicine, aiming for consensus. Lyso-GB3 is a valuable biomarker to establish the diagnosis. Proteinuria and creatinine are the most valuable to detect renal damage. Troponin I and high-sensitivity assays for cardiac troponin T can identify patients with cardiac lesions, but new techniques of cardiac imaging are essential to detect incipient damage. Specific cerebrovascular imaging findings are present in AFD patients. Techniques as metabolomics and proteomics have been developed in order to find an AFD fingerprint. Lyso-GB3 is important for evaluating the pathogenic mutations and monitoring the response to treatment. Many biomarkers can detect renal, cardiac and cerebrovascular involvement, but none of these have proved to be important to monitoring the response to treatment. Imaging features are preferred in order to find cardiac and cerebrovascular compromise in AFD patients.

Toluene exposure enhances acute and chronic formalin-induced nociception in rats: Participation of 5-HT3 receptors.

The purpose of this study was to evaluate the effect of acute toluene exposure on formalin (0.5% and 1%)-induced acute and long-lasting nociceptive hypersensitivity in rats. In addition, we sought to investigate the role of peripheral 5-HT3 receptors in the pronociceptive effect of toluene. Toluene exposure (6000ppm) for 30min enhanced 0.5% or 1% formalin-induced acute nociception and long-lasting secondary allodynia and hyperalgesia. In contrast, exposition to toluene for 30min in rats previously injected (six days before) with 1% formalin did not affect long-lasting hypersensitivy. Local peripheral pre-treatment with alosetron (5-HT3 receptor antagonist, 10-100 nmol) reduced the pronociceptive effect of toluene in acute nociception and long-lasting secondary allodynia and hyperalgesia. Alosetron (100nmol) was also able to reduce the nociceptive effects of 1% formalin in absence of toluene. Moreover, local peripheral injection of m-CPBG (5-HT3 receptor agonist, 300 nmol) enhanced 0.5% formalin-induced acute and long-lasting nociception in air- and toluene-exposed rats. Alosetron (10nmol) blocked the pronociceptive effects of m-CPBG (300nmol) on 0.5% formalin-induced acute and long-lasting hypersensitivity in rats exposed to toluene. Alosetron (at 10nmol) did not modify formalin-induced nociceptive behaviors. Finally, local peripheral pre-treatment with methiothepin (non-selective 5-HT receptor antagonist, 1.5nmol), did not affect the pronociceptive effect of toluene on 1% formalin-induced acute and long-lasting hypersensitivity. Our data demonstrate that acute exposure to toluene has pronociceptive effects in formalin-induced acute nociception and long-lasting hypersensitivity. Our data suggest that this pronociceptive effect depend on activation of peripheral 5-HT3, but not methiothepin-sensitive 5-HT, receptors.