Aquaporin-4 Antibodies Are Not Related to HTLV-1\ud Associated Myelopathy

Introduction: The seroprevalence of human T-cell leukemia virus type 1 (HTLV-1) is very high among Brazilians (,1:200).\ud HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the most common neurological complication of\ud HTLV-1 infection. HAM/TSP can present with an acute/subacute form of longitudinally extensive myelitis, which can be\ud confused with lesions seen in aquaporin-4 antibody (AQP4-Ab) positive neuromyelitis optica spectrum disorders (NMOSD)\ud on MRI. Moreover, clinical attacks in patients with NMOSD have been shown to be preceded by viral infections in around\ud 30% of cases.\ud Objective: To evaluate the frequency of AQP4-Ab in patients with HAM/TSP. To evaluate the frequency of HTLV-1 infection\ud in patients with NMOSD.\ud Patients and Methods: 23 Brazilian patients with HAM/TSP, 20 asymptomatic HTLV-1+ serostatus patients, and 34 with\ud NMOSD were tested for AQP4-Ab using a standardized recombinant cell based assay. In addition, all patients were tested for\ud HTLV-1 by ELISA and Western blotting.\ud Results: 20/34 NMOSD patients were positive for AQP4-Ab but none of the HAM/TSP patients and none of the\ud asymptomatic HTLV-1 infected individuals. Conversely, all AQP4-Ab-positive NMOSD patients were negative for HTLV-1\ud antibodies. One patient with HAM/TSP developed optic neuritis in addition to subacute LETM; this patient was AQP4-Ab\ud negative as well. Patients were found to be predominantly female and of African descent both in the NMOSD and in the\ud HAM/TSP group; Osame scale and expanded disability status scale scores did not differ significantly between the two\ud groups.\ud Conclusions: Our results argue both against a role of antibodies to AQP4 in the pathogenesis of HAM/TSP and against an\ud association between HTLV-1 infection and the development of AQP4-Ab. Moreover, the absence of HTLV-1 in all patients\ud with NMOSD suggests that HTLV-1 is not a common trigger of acute attacks in patients with AQP4-Ab positive NMOSD in\ud populations with high HTLV-1 seroprevalence.This study received financial support from the Brazilian government agencies FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo - www. fapesp.br/en) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - www.capes.gov.br). The work of S.J. and B.W. was supported by research grants from Bayer Schering Healthcare and from Merck Serono. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse

The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND). We provide evidence that MS patients in relapse without any treatment have a significantly (p < 0.01) higher percentage of pDCs in CSF than do patients in remission or those with OND. No change in the percentage of pDCs was observed in the peripheral blood of any of these patients. The increase of pDCs in central nervous system during relapse may be explained either by a virus infection or a down regulatory process

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

<p>Abstract</p> <p>Background</p> <p>Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.</p> <p>Methods</p> <p>This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.</p> <p>Discussion</p> <p>The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.</p> <p>Trial Registration</p> <p>Clinical Trials <a href="http://www.clinicaltrials.gov/ct2/show/NCT00970931">NCT00970931</a>.</p

Benefícios da ventilação não-invasiva após extubação no pós-operatório de cirurgia cardíaca Benefits of non-invasive ventilation after extubation in the postoperative period of heart surgery

OBJETIVO: Demonstrar os benefícios da utilização da ventilação não-invasiva (VNI) no processo de interrupção da ventilação mecânica, no pós-operatório de cirurgia cardíaca. MÉTODOS: Estudo prospectivo, randomizado e controlado, com 100 pacientes submetidos a cirurgia de revascularização do miocárdio ou cirurgia valvar. Os pacientes foram admitidos na Unidade de Terapia Intensiva (UTI), sob ventilação mecânica e randomizados posteriormente em grupo estudo (n= 50) que utilizou VNI com dois níveis pressóricos após a extubação por 30 minutos, e grupo controle (n= 50) que fez uso apenas de cateter nasal de O2. Foram analisadas as variáveis antropométricas, os tempos correspondentes à anestesia, cirurgia e circulação extracorpórea, bem como o tempo necessário para a supressão da ventilação mecânica invasiva. As variáveis gasométricas e hemodinâmicas também foram avaliadas antes e após a extubação. RESULTADOS: Os grupos controle e estudo evoluíram de forma semelhante e não apresentaram diferença estatisticamente significante na análise das variáveis, exceto para a PaO2. A utilização da VNI por 30 minutos após a extubação promoveu melhora na PaO2 quando comparados os grupos, com p= 0,0009, mas não apresentou diferença estatisticamente significante na PaCO2 (p=0,557). CONCLUSÃO: O uso da VNI por 30 minutos após extubação produziu melhora na oxigenação do pacientes em pósoperatório imediato de cirurgia cardíaca.<br>OBJECTIVE: to show the benefits of the use of non-invasive positive pressure ventilation (NPPV) in the process of weaning from mechanical ventilation in the immediate postoperative period of heart surgery. METHODS: A prospective, randomized and controlled study was performed involving 100 consecutive patients submitted to coronary artery bypass grafting or valve surgery. The subjects were admitted into the Intensive Care Unit (ICU) under mechanical ventilation and randomized in a study group (n=50), which used NPPV with bilevel pressure for 30 minutes after extubation, and a control group (n=50) which only used a nasal O2 catheter. Anthropometric variables and the times of the intra-operative periods corresponding to anesthesia, surgery and cardiopulmonary bypass, as well as the time required for weaning from invasive mechanical ventilation were analysed. The arterial blood gases and hemodynamic variables were also assessed before and after extubation. RESULTS: The evolution was similar for the control and study groups without statistically significant differences of the variables analyzed except for the PaO2. On comparing the groups, the PaO2 improved significantly (p = 0.0009) with the use of NPPV for 30 minutes after extubation, but there was no statistically significant difference in the PaCO2 (p = 0.557). CONCLUSION: The use of NPPV for 30 minutes after extubation improved oxygenation in the immediate postoperative period of heart surgery