Apical or Septal Right Ventricular Location in Patients Receiving Defibrillation Leads: A Systematic Review and Meta-Analysis.

This study reviews the published data comparing the efficacy and safety of apical and septal right ventricle defibrillator lead positioning at 1-year follow-up. Systemic research on Medline (PubMed), ClinicalTrials.gov, and Embase was performed using the keywords "septal defibrillation," "apical defibrillation," "site defibrillation," and "defibrillation lead placement," including implantable cardioverter-defibrillator and cardiac resynchronization therapy devices. Comparisons between apical and septal position were performed regarding R-wave amplitude, pacing threshold at a pulse width of 0.5 ms, pacing and shock lead impedance, suboptimal lead performance, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, readmissions due to heart failure and mortality rates. A total of 5 studies comprising 1438 patients were included in the analysis. Mean age was 64.5 years, 76.9% were male, with a median LVEF of 27.8%, ischemic etiology in 51.1%, and a mean follow-up period of 26.5 months. The apical lead placement was performed in 743 patients and septal lead placement in 690 patients. Comparing the 2 placement sites, no significant differences were found regarding R-wave amplitude, lead impedance, suboptimal lead performance, LVEF, left ventricular end-diastolic diameter, and mortality rate at 1-year follow-up. Pacing threshold values favored septal defibrillator lead placement (P = 0.003), as well as shock impedance (P = 0.009) and readmissions due to heart failure (P = 0.02). Among patients receiving a defibrillator lead, only pacing threshold, shock lead impedance, and readmission due to heart failure showed results favoring septal lead placement. Therefore, generally, the right ventricle lead placement does not appear to be of major importance.

Real-time PCR-based quantification of Toxoplasma gondii in tissue samples of serologically positive outdoor chickens.

This study aimed to quantify Toxoplasma gondii in tissue samples of serologically positive chickens using real-time polymerase chain reaction (PCR). Of 65 chickens evaluated, 28 were positive for T. gondii antibodies. Brain and heart samples were collected from 26 seropositive chickens and DNA was extracted using Trizol® and amplified using real-time PCR with SYBR® Green. Parasite DNA was detected in 24 of the 26 samples analyzed; the number of positive tissue samples and the parasite quantity did not differ between tissue types. The results confirmed the analytical sensitivity of parasite detection in chicken tissue samples and demonstrated the possibility of using other molecular systems for genotypic analysis.

Long-term follow-up of adult patients with congenital heart disease and an implantable cardioverter defibrillator.

OBJECTIVE: Sudden cardiac death is common in the adult congenital heart disease (ACHD) population. Knowledge and experience about the use of implantable cardioverter defibrillators (ICD) in ACHD patients is very limited. We aimed to characterize a cohort of patients with ACHD and ICDs. DESIGN: Thirty consecutive ACHD patients submitted to an ICD implantation in a single tertiary center were evaluated. Data on baseline clinical features, heart defect, indication for ICD, type of device, appropriate therapies, ICD-related complication, and mortality during follow-up were collected. RESULTS: Of the 30 patients, 56.7% received appropriate therapies due to ventricular tachycardia (VT) or ventricular fibrillation (VF). The rate of inappropriate therapies and device-related complications was 33.3%. Secondary prevention and primary prevention patients with class I indications for ICD had more appropriate therapies than complication, but this relationship was reversed for patients with class II indications. Remote monitoring played an important role in diagnosing new atrial arrhythmias before scheduled visits in 46.2% of patients, leading to a change in medication. VT/VF episodes were associated with a composite of death, cardiac transplantation, and hospital admission (OR 13.0; 95% CI: 2.1-81.5). CONCLUSION: ICDs are not only useful in preventing SCD, but also have a major role in diagnosing atrial tachyarrhythmias ahead of scheduled visits. Although improvements in ICD technology might reduce complications and inappropriate therapies, adequate selection of candidates for primary prevention still remains difficult because of the lack of clear indications.

A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex.

Bilateral adrenocortical hyperplasia (BAH) is the second most common cause of corticotropin-independent Cushing syndrome (CS). Genetic forms of BAH have been associated with complex syndromes such as Carney Complex and McCune-Albright syndrome or may present as isolated micronodular adrenocortical disease (iMAD) usually in children and young adults with CS. A genome-wide association study identified inactivating phosphodiesterase (PDE) 11A (PDE11A)-sequencing defects as low-penetrance predisposing factors for iMAD and related abnormalities; we also described a mutation (c.914A > C/H305P) in cyclic AMP (cAMP)-specific PDE8B, in a patient with iMAD. In this study we further characterize this mutation; we also found a novel PDE8B isoform that is highly expressed in the adrenal gland. This mutation is shown to significantly affect the ability of the protein to degrade cAMP in vitro. Tumor tissues from patients with iMAD and no mutations in the coding PDE8B sequence or any other related genes (PRKAR1A, PDE11A) showed downregulated PDE8B expression (compared to normal adrenal cortex). Pde8b is detectable in the adrenal gland of newborn mice and is widely expressed in other mouse tissues. We conclude that PDE8B is another PDE gene linked to iMAD; it is a candidate causative gene for other adrenocortical lesions linked to the cAMP signaling pathway and possibly for tumors in other tissues.

Impact on long-term cardiovascular outcomes of different cardiac resynchronization therapy response criteria.

INTRODUCTION: There is a lack of consensus on the definition of response to cardiac resynchronization therapy (CRT), and it is not clear which response criteria have most influence on cardiac event-free survival. OBJECTIVES: To assess the predictive value of various response criteria in patients undergoing CRT and the agreement between them. METHODS: We performed a secondary analysis of the BETTER-HF trial. Patient response was classified at six months after CRT according to eleven criteria used in previous trials. The predictive value of response criteria for survival free from mortality, cardiac transplantation and heart failure hospitalization was assessed by Cox regression analysis. Agreement between the different response criteria was assessed using Cohen's kappa (κ). RESULTS: A total of 115 patients were followed for a mean of 25 months. During follow-up, 15 deaths occurred (13%) and 29 patients had at least one adverse cardiac event (25%). Only five of the eleven response criteria were predictors of event-free survival. The most powerful isolated clinical and echocardiographic predictors were a reduction of ≥1 NYHA functional class (HR 0.39 for responders; 95% CI 0.18-0.83, p=0.014) and an increase of at least 15% in left ventricular ejection fraction (HR 0.43, 95% CI 0.20-0.90, p=0.024), respectively. Agreement between the different response criteria was poor. CONCLUSIONS: Most currently used response criteria do not predict clinical outcomes and have poor agreement. It is essential to establish a consensus on the definition of CRT response in order to standardize studies.

Complete gallbladder duplication: seventh report in world literature

Gallbladder duplication results from a rare abnormality of embriogenesis and is twice as common in women as in men. The signs and symptoms of double gallbladder cholecystitis are the same as those of single gallbladder cholecystitis: strong pain in the epigastric region and right hypochondrium, which may irradiate to the back and be accompanied by nausea and/or vomiting, Murphy positive sign, and pain on palpation of these regions; plastron may also be present. For this reason, many cases are still diagnosed intraoperatively, making surgery difficult and increasing the possibility of biliary tract injury. We report the case of a female patient with epigastric and dorsal pain for 4 days, which worsened with the ingestion of salty and fatty foods and was accompanied by nausea and vomiting. Physical examination showed a positive Murphy sign. A complete abdominal ultrasound examination showed gallbladder duplication, both lithiasic. Magnetic resonance cholangiography confirmed the duplication of the gallbladder and cystic ducts, with a single main biliary tract and acute lithiasic cholecystitis in both gallbladders. A laparoscopic cholecystectomy of both vesicles was performed without complications, and the patient was discharged 3 days after the procedure. (AU)

[Predictors of lack of clinical improvement at mid-term follow-up with cardiac resynchronization therapy]. / Predictores de ausencia de mejoría clínica a medio plazo con la terapia de resincronización cardíaca.

INTRODUCTION: About 30% of all patients do not respond to cardiac resynchronization therapy for heart failure. The objective of the study was to analyze the variables that may predict the lack of response. PATIENTS AND METHOD: We analyzed the results in a series of 63 patients who received cardiac resynchronization with a biventricular device. Clinical and left ventricular function parameters were evaluated at the beginning of the study and at 6 months. Responders were defined as those who were alive, had not received a heart transplant, and who achieved more than a 10% increase in distance in the 6-minute walking test. RESULTS: Mean age was 68.3 (8) years, 51 patients (81%) were men, and NYHA functional class was III-IV in 79.4%. Mean left ventricular ejection fraction was 22.4% (6)%, QRS width was 177 (25) ms, and 77.8% were in sinus rhythm. Almost half (46%, n=29) had ischemic heart disease. At 6-month follow-up, 69.8% of the patients were responders. Ischemic heart disease, sustained monomorphic ventricular tachycardia and a degree of mitral regurgitation >II/IV before implantation were associated with lack of response. No association was found for any of the other baseline variables. Logistic regression analysis identified all three of the aforementioned variables as independent predictors of lack of response: ischemic heart disease OR=4.8, 95% CI, 1.2-18.3, P=.023; ventricular tachycardia OR=8.7, 95% CI, 1.8-41.3, P=.007; and mitral regurgitation OR=8.03, 95% CI, 1.7-37.1, P=.008. CONCLUSION: The likelihood of responding to resynchronization therapy is lower in patients with ischemic heart disease, significant mitral regurgitation, or sustained monomorphic ventricular tachycardia.

Congenital absence of left pericardium.

The authors present a clinical case of right chamber dilatation in a 34-year-old patient with no symptoms, investigation of which led to a diagnosis of congenital absence of left pericardium, established by magnetic resonance imaging (MRI). They also present a review on absence of the pericardium, and discuss associated congenital abnormalities, the clinical presentations and findings in diagnostic tests, with particular emphasis on MRI.

Coronary spasm in acute myocardial infarction.

The authors present a clinical case of coronary spasm in acute myocardial infarction in a 22-year-old patient, admitted to the emergency department with chest pain. Angiography revealed normal coronary arteries and during the procedure a coronary spasm occurred.

Do patients with intraventricular gradients during dobutamine stress echocardiography have intraventricular gradients with exercise testing?

UNLABELLED: The development of intraventricular gradients during dobutamine stress echocardiography has been widely reported and this finding is commonly associated with symptoms during stress testing. In a previous study, we investigated the incidence of intraventricular gradients during dobutamine stress echocardiography in 46 patients and concluded that they occur frequently (43%). In another study we looked for the same phenomenon in 50 other consecutive patients during exercise stress echocardiography and only found a small gradient in one patient (2%). The purpose of the present study was to look for the development of intraventricular gradients during exercise echocardiography, in patients in whom this phenomenon occurred during dobutamine stress echocardiography. We studied 10 patients who developed a significant intraventricular gradient in a negative or inconclusive dobutamine stress echocardiography study. Five of the patients were male, mean age was 63 +/- 15.9 years (34-79). Three patients had previously undergone coronary angioplasty. The presence of intraventricular gradients was evaluated in all patients by color, pulsed and continuous wave Doppler echocardiography during dobutamine and exercise stress testing. An intraventricular gradient was considered significant when the intraventricular flow velocity increased by more than 1 m/s at the end of systole. The mean intraventricular gradient developed during dobutamine stress echocardiography was 101.7 +/- 68 mmHg (47-270). Only one of these patients developed a small intraventricular gradient during exercise stress echocardiography. CONCLUSION: In a small population of patients who developed significant intraventricular gradients during dobutamine stress echocardiography, this finding was not reproduced with exercise echocardiography.

Allele frequencies of 15 STRs in a representative sample of the Brazilian population.

Allele frequencies for 15 short tandem repeat (STR) loci were obtained from a sample of 12,030 individuals undergoing paternity testing. This sample includes individuals from all States in Brazil, combined according to the current country division into five regions (North, Northeast, Central West, Southeast, and South). The most polymorphic loci were D2S1338 and D18S51. All the analysed loci meet Hardy-Weinberg equilibrium expectations. Combined power of discrimination and combined power of exclusion for the 15 tested STR loci were 0.999999999999990 and 0.9999992, respectively. Comparative analysis between populations from different Brazilian macroregions as well as between Brazil and other relevant populations are presented.

15 STR loci frequencies in the population from Paraná, Southern Brazil.

Allele frequencies for 15 short tandem repeats (STR) loci were obtained from a sample of 4076 unrelated individuals undergoing paternity testing. The population is from Paraná, Southern Brazil. The loci are the most commonly used in forensic and paternity testing, being analyzed by the AmpFlSTR((R)) Identifiler (Applied Biosystems) commercial kit. The most polymorphic loci were D2S1338 and D18S51. Excepting the D13S317, all loci were in Hardy-Weinberg equilibrium. Comparative analyses between our population data and other populations are presented.

Functional phosphodiesterase 11A mutations may modify the risk of familial and bilateral testicular germ cell tumors.

Inactivating germline mutations in phosphodiesterase 11A (PDE11A) have been implicated in adrenal tumor susceptibility. PDE11A is highly expressed in endocrine steroidogenic tissues, especially the testis, and mice with inactivated Pde11a exhibit male infertility, a known testicular germ cell tumor (TGCT) risk factor. We sequenced the PDE11A gene-coding region in 95 patients with TGCT from 64 unrelated kindreds. We identified 8 nonsynonymous substitutions in 20 patients from 15 families: four (R52T, F258Y, G291R, and V820M) were newly recognized, three (R804H, R867G, and M878V) were functional variants previously implicated in adrenal tumor predisposition, and one (Y727C) was a known polymorphism. We compared the frequency of these variants in our patients to unrelated controls that had been screened and found negative for any endocrine diseases: only the two previously reported variants, R804H and R867G, known to be frequent in general population, were detected in these controls. The frequency of all PDE11A-gene variants (combined) was significantly higher among patients with TGCT (P = 0.0002), present in 19% of the families of our cohort. Most variants were detected in the general population, but functional studies showed that all these mutations reduced PDE activity, and that PDE11A protein expression was decreased (or absent) in TGCT samples from carriers. This is the first demonstration of the involvement of a PDE gene in TGCT, although the cyclic AMP signaling pathway has been investigated extensively in reproductive organ function and their diseases. In conclusion, we report that PDE11A-inactivating sequence variants may modify the risk of familial and bilateral TGCT.

Real-time PCR-based quantification of Toxoplasma gondii in tissue samples of serologically positive outdoor chickens

This study aimed to quantify Toxoplasma gondii in tissue samples of serologically positive chickens using real-time polymerase chain reaction (PCR). Of 65 chickens evaluated, 28 were positive for T. gondii antibodies. Brain and heart samples were collected from 26 seropositive chickens and DNA was extracted using Trizol® and amplified using real-time PCR with SYBR® Green. Parasite DNA was detected in 24 of the 26 samples analyzed; the number of positive tissue samples and the parasite quantity did not differ between tissue types. The results confirmed the analytical sensitivity of parasite detection in chicken tissue samples and demonstrated the possibility of using other molecular systems for genotypic analysis.

Short head-up tilt test potentiated with oral nitroglycerine: comparison with a conventional test using isoproterenol.

Conventional tilt test protocols are time consuming and there is no consensus regarding the optimal duration of the test and the provocative drug to be used. This study evaluated the diagnostic power of a short nitroglycerine test against a conventional isoproterenol protocol. A cohort of 128 patients with unexplained syncope was studied. A group of 64 consecutive patients were tilted with a short nitroglycerine test consisting of a passive phase of 15 minutes and if this proved negative, 400 microg of sublingual nitroglycerin spray for a further 15 minutes. The control group consisted of 64 patients tilted with a conventional isoproterenol protocol with a passive phase of 30 minutes and a drug-challenge phase of 20 minutes. In the nitroglycerine protocol 39 (60.9%) patients showed a positive response versus 27(42.2%) in the isoproterenol group (P = 0.034). The duration of the protocol was 23.2 +/- 7.2 minutes in the nitroglycerine group versus 41.1 +/- 15.5 minutes with isoproterenol (P = 0.001). The time until syncope was 18.87 +/- 6.1 versus 29 +/- 18, respectively (P = 0.002). For evaluating unexplained syncope the short tilt test protocol with nitroglycerine is less time consuming, easier to perform, and has a higher rate of positive response than a conventional isoproterenol protocol.

Validação do método de detecção de Chlamydia trachomatis por Reação em Cadeia da Polimerase em tempo real / Validation of a Chlamydia trachomatis detection method by Real Time Polymerase chain reaction

Infecções causadas por Chlamydia trachomatis são recentemente reconhecidas como as mais prevalentes e estão entre as mais prejudiciais doenças sexualmente transmissíveis (DST) no mundo. A ausência de sintomas dificulta o diagnóstico clínico das infecções clamidiais. Um dos desafios na prevenção das infecções causadas por C. trachomatis é a disponibilidade de diagnósticos laboratoriais com alta sensibilidade, especificidade e reprodutibilidade. No presente estudo, foi comparado o desempenho do testes de Reação em Cadeia da Polimerase (PCR) COBAS Amplicor® Chlamydia trachomatis (Roche) e PCR em tempo real (SYBR® – Green), usados para detecção de Chlamydia trachomatis em espécimes de urina e secreções urogenitais. O COBAS Amplicor® (Roche) é umteste de PCR convencional e foi usado como ferramenta para controle e teste de padrão ouro para diagnóstico no presente trabalho. Um total de 136 amostras de secreção endocervical (61), secreção uretral (14) e urina (61), foram obtidas de pacientes submetidos a testes de detecção de Chlamydia trachomatis no Laboratório Alvaro S/A. Os métodos de PCR em tempo real e COBAS Amplicor® (Roche)foram igualmente sensíveis para o diagnóstico de C. trachomatis em amostras de secreção uretral. Entretanto, em análises de urinae secreção endocervical o teste COBAS Amplicor® (Roche) mostrou 57% e 33% de positividade, respectivamente, contra 47% e 24% de positividade obtidos para as mesmas amostras usando a PCR em tempo real. A maior sensibilidade (100%) obtida usando-seo ensaio de PCR em tempo real, foi em análises das amostras de secreção endocervical. A PCR em tempo real, comparada com o teste padrão ouro, mostrou uma alta especificidade (100%) e um valor preditivo positivo de 100% para as diferentes amostras clínicas estudadas. Em conclusão, os dados apresentados neste estudo indicam que a PCR em tempo real mostrou um alto desempenho para detecção de C. trachomatis em diferentes espécimes clínicos...

Infections caused by Chlamydia trachomatis are now recognized as the most prevalent and are among the most damaging of all sexually transmitted diseases (STD) worldwide. Lack of symptoms makes clinical diagnosis of chlamydial infection difficult. One of the challenge in the prevention of C. trachomatis infections is the availability of laboratory diagnostics with high sensitivity, specificity and reliable. In the present study, the performance of conventional polymerase chain reaction (PCR) and Real-time PCR (SYBRR –Green) tests used for detection of Chlamydia trachomatis in urine and urogenital specimens were compared. The COBAS AmplicorR (Roche) is a conventional PCR and was used as a tool of control and gold standard test for diagnosis in this work. A total of 136 samples of endocervical secretion (61), uretral secretion (14) and urine (61), were obtained from patients submitted of Chlamydia trachomatis detection tests of Laboratório Alvaro S/A. Real-time PCR (SYBRR –Green) and COBAS AmplicorR Chlamydia trachomatis Test (Roche) methods were equally sensitivity for diagnostic of C. trachomatis in uretral secretion samples. However, in analyses of the urine and endocervical secretion samples the COBAS AmplicorR test displayed 57% and 33% of positivity, recpectively, against 47% and 24% of positivity obtained for the same samples using Real-time PCR. The highest sensibility (100%) using Real-timePCR assay was obtained in analyses of endocervical secretion samples. Real-time PCR, comparing with our gold standard showed a high spedificity (100%) and a positive predictive value of 100% for different clinical samples studied. In conclusion, the data presented in this study indicate that PCR - Real time have shown a high performance for detection of C. trachomatis in different clinical specimens. Moreover, this method can be used as a powerful tool in diagnostic and epidemiological investigation of infection associated with C. trachomatis.