Dispersão da Refractariedade Auricular como Substrato Electrofisiológico da Vulnerabilidade Auricular em Doentes com Fibrilhação Auricular Paroxística

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.

Effects of Acute Autonomic Modulation on Atrial Conduction Delay and Local Electrograms Duration in Paroxysmal Atrial Fibrillation

Slowed atrial conduction may contribute to reentry circuits and vulnerability for atrial fibrillation (AF). The autonomic nervous system (ANS) has modulating effects on electrophysiological properties. However, complex interactions of the ANS with the arrhythmogenic substrate make it difficult to understand the mechanisms underlying induction and maintenance of AF. AIM: To determine the effect of acute ANS modulation in atrial activation times in patients (P) with paroxysmal AF (PAF). METHODS AND RESULTS: 16P (9 men; 59±14years) with PAF, who underwent electrophysiological study before AF ablation, and 15P (7 men; 58±11years) with atrioventricular nodal reentry tachycardia, without documentation or induction of AF (control group). Each group included 7P with arterial hypertension but without underlying structural heart disease. The study was performed while off drugs. Multipolar catheters were placed at the high right atrium (HRA), right atrial appendage (RAA), coronary sinus (CS) and His bundle area (His). At baseline and with HRA pacing (600ms, shortest propagated S2) we measured: i) intra-atrial conduction time (IACT, between RAA and atrial deflection in the distal His), ii) inter-atrial conduction time (interACT, between RAA and distal CS), iii) left atrial activation time (LAAT, between atrial deflection in the distal His and distal CS), iv) bipolar electrogram duration at four atrial sites (RAA, His, proximal and distal CS). In the PAF group, measurements were also determined during handgrip and carotid sinus massage (CSM), and after pharmacological blockade of the ANS (ANSB). AF was induced by HRA programmed stimulation in 56% (self-limited - 6; sustained - 3), 68.8% (self-limited - 6; sustained - 5), and 50% (self-limited - 5; sustained - 3) of the P, in basal, during ANS maneuvers, and after ANSB, respectively (p=NS). IACT, interACT and LAAT significantly lengthened during HRA pacing in both groups (600ms, S2). P with PAF have longer IACT (p<0.05), a higher increase in both IACT, interACT (p<0.01) and electrograms duration (p<0.05) with S2, and more fragmented activity, compared with the control group. Atrial conduction times and electrograms duration were not significantly changed during ANS stimulation. Nevertheless, ANS maneuvers increased heterogeneity of the local electrograms duration. Also, P with sustained AF showed longer interACT and LAAT during CSM. CONCLUSION: Atrial conduction times, electrograms duration and fractionated activity are increased in PAF, suggesting a role for conduction delays in the arrhythmogenic substrate. Acute vagal stimulation is associated with prolonged interACT and LAAT in P with inducible sustained AF and ANS modulation may influence the heterogeneity of atrial electrograms duration.

Inducibility of Atrial Fibrillation During Electrophysiologic Evaluation is Associated with Increased Dispersion of Atrial Refractoriness

The impact of atrial dispersion of refractoriness (Disp_A) in the inducibility and maintenance of atrial fibrillation (AF) has not been fully resolved. AIM: To study the Disp_A and the vulnerability (A_Vuln) for the induction of self-limited (<60 s) and sustained episodes of AF. METHODS AND RESULTS: Forty-seven patients with paroxysmal AF (PAF): 29 patients without structural heart disease and 18 with hypertensive heart disease. Atrial effective refractory period (ERP) was assessed at five sites--right atrial appendage and low lateral right atrium, high interatrial septum, proximal and distal coronary sinus. We compared three groups: group A - AF not inducible (n=13); group B - AF inducible, self-limited (n=18); group C - AF inducible, sustained (n=16). Age, lone AF, hypertension, left atrial and left ventricular (LV) dimensions, LV systolic function, duration of AF history, atrial flutter/tachycardia, previous antiarrhythmics, and Disp_A were analysed with logistic regression to determine association with A_Vuln for AF inducibility. The ERP at different sites showed no differences among the groups. Group A had a lower Disp_A compared to group B (47+/-20 ms vs 82+/-65 ms; p=0.002), and when compared to group C (47+/-20 ms vs 80+/-55 ms; p=0.008). There was no significant difference in Disp_A between groups B and C. By means of multivariate regression analysis, the only predictor of A_Vuln was Disp_A (p=0.04). Conclusion: In patients with PAF, increased Disp_A represents an electrophysiological marker of A_Vuln. Inducibility of both self-limited and sustained episodes of AF is associated with similar values of Disp_A. These findings suggest that the maintenance of AF is influenced by additional factors.

Acute Bivalvular Left-Sided Methicillin-Resistant Staphylococcus Aureus Endocarditis with Cardiac, Cerebral, Renal and Septic Complications

Infective endocarditis (IE) is now rare in developed countries, but its prevalence is higher in elderly patients with prosthetic valves, diabetes, renal impairment, or heart failure. An increase in health-care associated IE (HCAIE) has been observed due to invasive maneuvers (30% of cases). Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus are the most common agents in HCAIE, causing high mortality and morbidity. We review complications of IE and its therapy, based on a patient with acute bivalvular left-sided MRSA IE and a prosthetic aortic valve, aggravated by congestive heart failure, stroke, acute immune complex glomerulonephritis, Candida parapsilosis fungémia and death probably due to Serratia marcescens sepsis. The HCAIE was assumed to be related to three temporally associated in-hospital interventions considered as possible initial etiological mechanisms: overcrowding in the hospital environment,iv quinolone therapy and red blood cell transfusion. Later in the clinical course,C. parapsilosis and S. marcescens septicemia were considered to be possible secondary etiological mechanisms of HCAIE.

Enfarte Agudo do Miocárdio Associado a Origem Anómala das Artérias Coronárias (um Caso Raro de Origem da Artéria Coronária Direita)

A origem da artéria coronária esquerda a partir do ostio ou do segmento proximal da artéria coronária direita é uma anomalia congénita rara (0,03 a 0,4%), e um achado angiográfico pouco comum (0,6 a 1,3%) (artéria coronária única). A anomalia congénita coronária mais frequente é a origem separada da artéria descendente anterior e da artéria circunflexa no seio coronário esquerdo. A segunda anomalia mais comum é a origem da artéria circunflexa no seio coronário direito. Descrevemos um caso de enfarte agudo do miocárdio com localização infero lateral, que evoluiu com choque cardiogénico e disfunção ventricular esquerda graves, após angioplastia primária de oclusão proximal da artéria coronária direita, e em que não foi possível cateterizar a artéria coronária esquerda por inexistência de ostio no seio coronário esquerdo. Destaca-se o papel importante das novas técnicas de imagem, nomeadamente da angio-TC das coronárias, na identificação das anomalias congénitas das artérias coronárias.

Digit Ratio (2D:4D) in Newborns: Influences of Prenatal Testosterone and Maternal Environment

Introduction: The 2D:4D digit ratio is sexually-dimorphic, probably due to testosterone action through the perinatal period. We characterize the 2D:4D ratio in newborn (NB) infants, in between the pre- and postnatal surges of testosterone, and relate it to the mother's 2D:4D and to testosterone levels in the amniotic fluid (AF). Subjects and methods: Testosterone was assayed in samples of maternal plasma and AF collected at amniocentesis. Shortly after birth, 106 NBs and their mothers were measured for 2D:4D ratio. Results: NB males had lower mean 2D:4D ratios than females but this dimorphism was significant only for the left hand (males: 0.927; females: 0.950; p=0.004). Mothers who had sons had lower 2D:4D ratios than those who had daughters and the mother's 2D:4D were higher than those of NBs regardless of sex. Both hands of NB females were negatively correlated with AF testosterone and positively correlated with the mother's 2D:4D, but males showed no significant associations. Maternal plasma testosterone also showed a negative weak correlation with NB's digit ratio in both sexes. Conclusions: Sexual dimorphism at birth was only significant for the left hand, in contrast with reports of greater right hand dimorphism, suggesting that postnatal testosterone is determinant for 2D:4D stabilization. The lower 2D:4D ratios in mothers who had sons support claims that hormone levels in parents are influential for determining their children's sex. NB female's digit ratio, but not males', was associated to the level of AF testosterone. The mother's 2D:4D ratios were positively correlated with their daughters' 2D:4D, but the same was not observed for male NBs, suggesting that prenatal testosterone levels in male fetus lead their 2D:4D ratios to stray from their mothers' with high individual variability.

Prostatic Arterial Supply: Anatomic and Imaging Findings Relevant for Selective Arterial Embolization

PURPOSE: To describe the anatomy and imaging findings of the prostatic arteries (PAs) on multirow-detector pelvic computed tomographic (CT) angiography and digital subtraction angiography (DSA) before embolization for symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: In a retrospective study from May 2010 to June 2011, 75 men (150 pelvic sides) underwent pelvic CT angiography and selective pelvic DSA before PA embolization for BPH. Each pelvic side was evaluated regarding the number of independent PAs and their origin, trajectory, termination, and anastomoses with adjacent arteries. RESULTS: A total of 57% of pelvic sides (n = 86) had only one PA, and 43% (n = 64) had two independent PAs identified (mean PA diameter, 1.6 mm ± 0.3). PAs originated from the internal pudendal artery in 34.1% of pelvic sides (n = 73), from a common trunk with the superior vesical artery in 20.1% (n = 43), from the anterior common gluteal-pudendal trunk in 17.8% (n = 38), from the obturator artery in 12.6% (n = 27), and from a common trunk with rectal branches in 8.4% (n = 18). In 57% of pelvic sides (n = 86), anastomoses to adjacent arteries were documented. There were 30 pelvic sides (20%) with accessory pudendal arteries in close relationship with the PAs. No correlations were found between PA diameter and patient age, prostate volume, or prostate-specific antigen values on multivariate analysis with logistic regression. CONCLUSIONS: PAs have highly variable origins between the left and right sides and between patients, and most frequently arise from the internal pudendal artery.

Transoesophageal Echocardiography for Monitoring Liver Surgery: Data from a Pilot Study

A pilot study aimed to introduce intraoperative monitoring of liver surgery using transoesophageal echocardiography (TEE) is described. A set of TEE measurements was established as a protocol, consisting of left atrial (LA) dimension at the aortic valve plane; mitral velocity flow integral, calculation of stroke volume and cardiac output (CO); mitral annular plane systolic excursion; finally, right atrial area. A total of 165 measurements (on 21 patients) were performed, 31 occurring during hypotension. The conclusions reached were during acute blood loss LA dimension changed earlier than CVP, and, in one patient, a dynamic left ventricular (LV) obstruction was observed; in 3 patients a transient LV systolic dysfunction was documented. The comparison between 39 CO paired measurements obtained by TEE and PiCCO2 revealed a statistically significant correlation (P < 0.001, r = 0.83). In this pilot study TEE successfully answered the questions raised by the anesthesiologists. Larger cohort studies are needed to address this issue.

Mosaic Trisomy 18 in a Five-Month-Old Infant - Case Report

Individuals with mosaic trisomy 18, only approximately 5% of all trisomy 18 cases, carry both a trisomy 18 and an euploid cell line. Their clinical findings are highly variable, from the absence of dysmorphic features to the complete trisomy 18 syndrome. A five month old daughter of a 38-year-old mother, with vomiting and feeding problems, was referred to our department. She was undernourished and had axial hypotony and developmental delay, an irregular pattern of hypopigmentation on the right side of the abdomen, and moderate sagittal body asymmetry with left-side muscular hemihypotrophy.Mild craniofacial dysmorphy included dolichocephaly, frontal bossing, prominent occiput, long downslanting palpebral fissures, hypertelorism, and retrognathia. A complex heart defect with atrial and ventricular septal defects, pulmonary artery stenosis, and bicuspid aortic valve was identified. Cytogenetic analysis revealedmosaic trisomy 18with trisomy in 90%of peripheral lymphocytes and 17%of skin fibroblasts.This case adds to our knowledge of the phenotypic spectrum and the natural history of mosaic trisomy 18 by adding a dysmorphic feature and a cardiac abnormality that, to the best of our knowledge, had not been previously described.

Interface Humana Músculo-Facial

Esta dissertação tem como principal objetivo a criação de uma interface humana, baseada na eletromiografia dos músculos orbicular do olho e frontalis. O algoritmo de programação do microcontrolador ATmega2560 deteta o piscar de olhos voluntário, conta o número de vezes que este acontece e verifica se preenche os requisitos necessários à execução de um comando. Para este efeito foram utilizados elétrodos para a captação do sinal eletromiográfico. O sinal analógico é condicionado pela Shield ECG/EMG da Olimex sendo enviado para o arduíno ATmega2560. Este microcontrolador administra todos os atuadores, dos quais o mais importante é um painel de comandos (quatro comandos diferentes), no qual existe um ponteiro motorizado que indica qual a ação a realizar. O código de execução é extremamente simples:  se o utilizador piscar os olhos três vezes, o ponteiro movimenta-se para a secção do painel imediatamente à direita; e  se o utilizador piscar os olhos quatro vezes, o ponteiro movimenta-se para a secção do painel imediatamente à esquerda. Os testes realizados com este dispositivo indicam que os utilizadores demoram menos de 10 minutos a aprender a utilizar e executar todos os comandos do painel. Apenas num dos testes realizados o dispositivo não funcionou. Dos utilizadores que realizaram o teste:  vários usam óculos;  um idoso com graves problemas auditivos, cegueira parcial e dificuldades locomotoras;  nenhum foi incapaz de piscar, pelo menos, um dos olhos voluntariamente; e  a maioria referiu que, com alguma concentração e principalmente se ouvirem o bip sonoro, a aprendizagem de utilização torna-se muito fácil. Apesar dos limites impostos à concretização de um projeto deste tipo (dos quais se evidenciam as dificuldades em conseguir voluntários com paralisia medular, bem como os limites orçamentais), pode-se afirmar que este dispositivo é eficaz e seria uma mais valia quando implementado num cenário de paralisia medular (total ou parcial). A melhoria de qualidade de vida de um utilizador com estes problemas físicos, ou outros que lhe comprometam a locomoção é garantida. O cenário em que vivem é tremendamente limitado sendo urgente criar soluções para tornar estas vidas mais cómodas. Com os devidos aplicativos, o utilizador poderia abrir portas ou janelas, acender ou apagar luzes, pedir ajuda, ajustar a posição da cama, controlar cadeiras de rodas, entre outros. É neste sentido que surge a minha motivação de criar algo que ajude estas pessoas.

Recalcitrant Leg Ulcers as the Only Manifestation of Essential Type 2 Cryoglobulinemia

Chronic leg ulcers are persistent conditions that might be a diagnostic and therapeutic challenge, with great impact in health care costs and patients’ quality of life. We report a case of a 60-year-old woman, with long-lasting recalcitrant leg ulcers, which led to left leg amputation 10 years ago. Several attempts to heal the right leg were made, including skin grafting in three different occasions and several surgical debridements, all with unsatisfactory outcome. Some months before the ulcers began, the patient had been diagnosed with undifferentiated connective tissue disease because of arthralgia and positive antinuclear antibodies, therefore low dose systemic corticosteroids and azathioprine were prescribed. For the last 4 years she has been followed in our department and since then no evidence of clinical or laboratorial criteria for autoimmune diseases was found, thus the immunosuppressive therapy was stopped. She maintained ever since a high rheumatoid factor but without other evidence of autoimmune disease. Medical history was otherwise irrelevant. Several cutaneous biopsies were performed, with no evidence of malignancy or vasculitis. Recently, cryoglobulins became positive, with type 2b cryoglobulin identification on immunofluorescence. Serology for Hepatitis C virus was consistently negative, hence an Essential type 2 Cryoglobulinemia diagnosis was established. No renal impairment, vascular purpura, arthralgia or arthritis was found. The authors emphasize the importance of considering less common etiologies for chronic leg wounds, even in the absence of other suggestive symptomatology, as well as the pertinence of reconsidering diagnosis in highly suspect cases.

Amaurose súbita e doença falciforme: a propósito de um caso

Os autores apresentam o caso clínico de uma criança com doença falciforme, internada por choque séptico com meningite e pneumonia a Streptococcus pneumoniae. No decurso do internamento surgiu amaurose súbita à esquerda e herpes mucocutâ- neo labial. O exame oftalmológico foi sugestivo de oclusão arterial no olho esquerdo e de necrose retiniana viral à direita, pelo que foi instituída terapêutica antiviral e anticoagulante. A evolução clínica e imagiológica foi compatível com necrose retiniana aguda. Verificou-se ligeira melhoria da acuidade visual à direita (6/10) mas persistiu um défice grave da acuidade visual à esquerda (< 1/10). A necrose retiniana aguda é um evento raro em idade pediátrica, cujo diagnóstico diferencial inclui outras causas de amaurose súbita.

No right to perform a contract?

Thesis submitted in Trinity Term 2001 for the degree of Master of Philosophy, Worcester College, Oxford

Breast Cancer Presents With a Paraneoplastic Neurologic Syndrome

BACKGROUND: Paraneoplastic neurologic syndromes (PNS) pose quite an uncommon neurological complication, affecting less than 1% of patients with breast cancer. Nearly one third of these patients lack detectable onconeural antibodies (ONAs), and improvement in neurologic deficits with concomitant cancer treatments is achieved in less than 30% of cases. CASE PRESENTATION: A 42-year-old, premenopausal woman presented with facial paralysis on the central left side accompanied by a left tongue deviation, an upward vertical nystagmus, moderate spastic paraparesis, dystonic posturing of the left foot, lower limb hyperreflexia and bilateral extensor plantar reflex. After ruling out all other potential neurologic causes, PNS was suspected but no ONAs were found. A PET-CT scan detected increased metabolism in the right breast, as well as an ipsilateral thoracic interpectoral adenopathy. Core biopsy confirmed the presence of an infiltrating duct carcinoma. After breast surgery, the neurologic symptoms disappeared. One week later, the patient was readmitted to the hospital with a bilateral fatigable eyelid ptosis, and two weeks later, there was a noticeable improvement in eyelid ptosis, accompanied by a rapid and progressive development of lower spastic paraparesis. She started adjuvant treatment with chemotherapy with marked clinical and neurological improvement, and by the end of radiotherapy, there were no signs of neurologic impairment. CONCLUSION: This case study highlights the importance of a high level of vigilance for the detection of PNS, even when ONAs are not detected, as the rapid identification and treatment of the underlying tumor offers the best chance for a full recovery.