The pressor response to acute hyperlipidemia is enhanced in lean normotensive offspring of hypertensive parents

Family history is an important predictor of the cardiovascular risk factor cluster associated with insulin resistance. The dyslipidemia associated with insulin resistance may contribute to elevated blood pressure (BP). This study was undertaken to further explore the link between family history, dyslipidemia, and BP regulation. Twenty-three lean normal volunteers with a negative family history (FH-, n = 11) or positive family history (FH+, n = 12) of hypertension were evaluated under baseline conditions and during a 4-h infusion of intralipid and heparin (acute hyperlipidemia). Fasting blood was drawn for lipids including nonesterified fatty acids (NEFA). After 2 and 4 h of intralipid and heparin, blood was drawn for NEFA. The BP was measured at baseline and every 30 min after starting the intralipid and heparin infusion. Baseline triglycerides and very low density lipoprotein cholesterol concentrations were higher in FH+ than FH- subjects (P < .05). However, NEFA increased similarly in both groups during the infusion of intralipid and heparin. The BP and heart rate increased with acute hyperlipidemia in all subjects combined (P < .05). Despite the similar increase of NEFA, mean BP, pulse pressure, and pressure-rate product increased significantly in FH+ subjects but not in FH- volunteers with acute hyperlipidemia. Although systolic BP increased in both groups, the increase was greater in FH+ than in FH- volunteers during acute hyperlipidemia (14 +/- 2 v 10 +/- 2 mm Hg, P < .05). These results suggest that higher plasma lipids combined with a greater pressor response to hyperlipidemia may contribute to the development of high BP in subjects with a family history of hypertension.     

Single-step transvenous extraction of a passive fixation lead with delayed perforation of the right ventricle

Delayed pacemaker lead perforation is a very rare complicationand most of the published reports involve active fixation leads.The authors report an uneventful transvenous extraction of apassive fixation lead, which had a delayed perforation of theright ventricle, disclosed two months after pacemaker implantation.     

Dysplasia in Barrett's esophagus--intra- and interobserver variability in histopathological diagnosis

BACKGROUND: Barrett's esophagus is a well-known pre-malignant condition. Pathologic interpretation of biopsy specimens guides endoscopic surveillance as well as the therapeutic approach that will be carried out. However, the predictive value of histopathologic diagnosis can be questioned due to its poor intra- and interobserver reproducibility. AIMS: To assess intra- and interobserver variability in the diagnosis of Barrett's dysplasia. MATERIAL AND METHODS: Three-micrometer thick sections from biopsy specimens from 42 patients with Barrett's esophagus were stained with hematoxylin-eosin and PAS-alcian blue. The reading of the slides was carried out blindly in a light microscope. Intra and interobserver variability in the interpretation of the slides was determined by kappa statistics. RESULTS: The number of tissue specimens was 229, with average of 5.45 (1 to 18) fragments for patient. Low grade dysplasia was diagnosed by pathologists in 21.4% to 52.4% of the cases. The intra-observer agreement for the diagnosis of low grade dysplasia was slight (kappa = 0.30). The interobserver agreement for the diagnosis of low grade dysplasia was poor, with kappa scores between 0.05 and 0.16. The diagnosis of dysplasia, with agreement for all pathologists examining the same set of slides, was 14.3%. CONCLUSIONS: Pathologic interpretation of Barrett's dysplasia may be subject to marked intra- and interobserver variabiliaty. Interpretation of low grade dysplasia, as high grade dysplasia, should also be considered for review by two or more pathologists.     

Comparison of an intravenous pulse of methylprednisolone versus oral corticosteroid in severe acute rheumatic carditis: a randomized clinical trial

OBJECTIVES: To compare the short-term prognosis of patients with severe acute rheumatic carditis when treated with an intravenous pulse of methylprednisolone in comparison with conventional treatment using oral prednisone. METHODS: We designed a randomized clinical trial in the setting of a university general hospital in Brazil. We randomly allocated 18 patients with the diagnosis of severe acute rheumatic carditis and congestive heart failure to receive an intravenous pulse as opposed to oral prednisolone. Methylprednisolone was administered in a dose of 1 g intravenously for 3 consecutive days in the first and second weeks, for two days in the third, and one day in the fourth week. Prednisone was administered in a dose of 1.5 mg/kg/day over the period of 4 weeks. RESULTS: The mean age of the patients was 11.1 +/- 3.7 years, with a median of 12 years. Patients on oral treatment showed a more pronounced decrease in the heart rate, sedimentation rate, and in the titres of C-reactive protein than those receiving intravenous therapy. At the end of treatment, a mild decrease in the left ventricular end-systolic dimension was found in those having oral treatment, compared to an increase in the group having intravenous treatment (p = 0.036). The ejection fraction showed a median increase of 5% in those undergoing oral treatment, and a median decrease of 6% in the group with intravenous therapy (p = 0.009). There were 5 therapeutic failures in those receiving intravenous therapy (56%), including 1 death. Therapeutic failures were not observed in those treated orally (p = 0.03). CONCLUSION: Intravenous treatment of methylprednisolone, as a single anti-inflammatory agent, was inferior to conventional treatment with oral prednisone in the control of severe rheumatic carditis.     

1002-LB: ACE Polymorphism in asthmatic patients

Aim

The aim of the this study was to analyse if there is an association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism (287 base pairs, on chromosome 17q23, intron 16) with asthma severity . ACE plays a vital role in the renin-angiotensin-system (RAS) which regulates blood pressure by converting angiotensin I into a powerfull vasoconstrictor angiotensin II and could also have a role in bronchoconstriction and airway remodeling in asthmatic disease.

Methods

Asthmatic patients: n = 22;were compared with a control group of n = 206 healthy blood donors. The insertion/deletion (I/D) polymorphism was determined by PCR- Polymerase chain reaction. Control of asthma assessed by validated instrument (ACQ7 and PAQLQ). Statistical analysis was performed with PASW 18, establishing a significance level of p< 0.05. All patients signed an informed consent.

Results

The mean age of the 22 asthmatics was 42.86 ± 20.8 years; 9 females and 13 males; all caucasians; 20 atopic and 2 nonatopic. The mean age of the control-group (n = 206) was 41.05 ± 11.85 years; 70 females and 136 males. In asthmatics the frequencies of the D- Allele (ACE-D) is 0.591 and of the IAllele (ACE-I) is 0.409; in controls: 0.675 and 0.325 respectively. There is no statistical differences between these groups (p = 0.340). Genotypes in the asthmatics- DD: 45.4%; ID: 27.3%; II: 27,3%; in control group- DD:48.1%; ID:38.8%; II: 13.1%. There is no statistical differences between these groups (p = 0,175). In asthmatics, there is no statistical differences in genotype frequencies (p > 0.05) between : atopics and non atopics; controlled and uncontrolled asthma; males and females; and in the different age-groups.

Conclusions

The role of ACE insertion/deletion (I/D) polymorphism, in asthmatic patients is a controversy risk factor to the severity of asthma, but we think that we need a larger sample to infer about its role in remodeling, vascular tonus and bronchoconstriction.     

Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-d-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser⁸⁴⁵ in the Ctx and GluR1-Ser⁸³¹ in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.     

Immunization with plasmids encoding M2 acetylcholine muscarinic receptor epitopes impairs cardiac function in mice and induces autophagy in the myocardium

Abstract

Autoantibodies against the M2 subtype of muscarinic acetylcholine receptors with functional activities have been found in the sera of patients with dilated cardiomyopathy (DCM), and the second extracellular loop has been established as the predominant epitope. However, it has been shown that the third intracellular loop is recognized by Chagas disease patients with severe cardiac dysfunction. In this work, BALB/c mice were immunized with plasmids encoding these two epitopes, and a control group received the empty plasmid (pcDNA3 vector). Serum from these DNA-immunized animals had elevated and persistent titres of antibodies against respective antigens. Heart echocardiography indicated diminished left ventricular wall thickness and reduced ejection fraction for both epitope-immunized groups, and ergospirometry tests showed a significant decrease in the exercise time and oxygen consumption. Transfer of serum from these immunized mice into naïve recipients induced the same alterations in cardiac structure and function. Furthermore, electron microscopy analysis of donor-immunized animals revealed several ultrastructural alterations suggestive of autophagy and mitophagy, suggesting novel roles for these autoantibodies. Overall, greater functional and structural impairment was observed in the donor and recipient epitope groups, implicating the third intracellular loop epitope in the pathological effects for the first-time. Therefore, the corresponding peptides could be useful for autoimmune DCM diagnosis and targeted therapy.     

Are there really many runners out there? Is the proportion of runners increasing over time? A population-based 12-year repeated cross-sectional study with 625,460 Brazilians

ObjectivesTo investigate the proportion of individuals who practice running, its temporal trend, and to describe the runners’ characteristics.DesignPopulation-based repeated cross-sectional study.MethodsThe data from the Protective and Risk Factors for Chronic Diseases by Telephone Survey (Vigitel) from Brazil were used. Telephone interviews were conducted with adults from the Brazilian capitals (27 cities) between 2006–2017. The interviewer read the questions and recorded the participants’ responses immediately in a questionnaire. Data analyses were conducted using a Bayesian approach.ResultsThe Vigitel database consisted of 625,460 Brazilian participants composed of 295,681 exercisers and within them 15,529 runners. The mean yearly proportion of runners was about 2.45% (95% Bayesian credible interval [CrI] 1.93 to 3.11) and 5.32% (95%CrI 4.29 to 6.54) in the entire study population and within exercisers, respectively. The absolute increase in the proportion of runners per year over the 12-year period was 0.13% and 0.17% in the entire study population and within exercisers, respectively. Runners were more likely to be younger, men, within normal body mass index, highly educated, moderate alcohol drinkers, non-smokers, less exposed to TV, living near physical activity/sports facilities and less exposed to health conditions such as arterial hypertension, diabetes and dyslipidaemia.ConclusionThere was a 95% probability that the yearly proportion of runners lies between 1.93% and 3.11% in the population of the 27 Brazilian capitals, and between 4.29% and 6.54% within exercisers. There has been an increase in the proportion of runners over time. Runners were associated with healthier characteristics compared to non-runners and non-exercisers.     

Comparative analysis of routine parasitological methods for recovery of cysts,molecular detection,and genotyping of Giardia duodenalis

European Journal of Clinical Microbiology & Infectious Diseases - In order to improve the diagnosis of giardiasis, fecal samples (high/medium/low concentration of cysts) were processed by the...     

Inappropriate screening of obstructive coronary artery disease during pre-anesthesia assessment of candidates for non-cardiac surgery

Preoperative evaluation in elective surgeries has been associated with successful surgical treatment. However, there is no solid scientific evidence that screening for coronary artery disease (CAD) reduces surgical risk. The aims of this study were to describe the frequency of inappropriate investigation of obstructive CAD induced by pre-anesthetic assessment in individuals without cardiovascular symptoms (candidates for low- to intermediate-risk surgeries) and to evaluate predictors of this conduct. We performed a retrospective evaluation of medical records of anesthesiology services from patients undergoing pre-anesthesia assessment between May 2015 and May 2016, including those with functional capacity ≥4 metabolic equivalents without a diagnosis of heart disease. A total of 778 medical records (47±16 years of age, 62.6% female) were studied. A private hospital performed 50.1% of the surgeries and 60.4% were of intermediate risk. Only 2.7% (95%CI: 1.7-4.1%) were screened for CAD, and 91% of these requests were mediated by cardiology consultations performed during pre-anesthetic testing visits. Factors associated with screening for CAD were hypertension, diabetes, moderate systemic disease (ASA III), cardiac consultation, previous diagnosis of CAD, and admission to a private hospital. Independent predictors were private hospitals (OR: 3.9; 95%CI: 1.3-11.0), ASA III (OR: 5.3; 95%CI: 1.7-16.2), and hypertension (OR: 3.8; 95%CI: 1.5-9.8). The frequency of inappropriate requests for CAD screening in asymptomatic individuals without untreated systemic diseases was low in pre-anesthetic visits. Although infrequent, screening for CAD is more common in the private setting, in patients with poorer health status, and is usually prescribed during cardiology consultation.