SED-brachydactyly and distinctive speech: Report of a new familial case

Background: Spondyloepiphyseal dysplasia-brachydactyly and distinctive speech (SED-BDS) is a syndrome characterized by short stature, disproportionately short limbs, peculiar face, thick and abundant hair, high-pitched and coarse voice, small epiphyses, brachymetacarpalia, brachymetatarsalia and brachy-phalangia of fingers and toes, small pelvis and delayed carpal bone age, among other features. Case Report: We report a Brazilian patient with father, brother and sister presenting with the same typical features of the syndrome. Clinically, he showed disproportionately short stature, rhizo-meso-acromelic shortness of the extremities, short hands and feet, a peculiar distinctive high-pitched voice, peculiar facies, and other features already reported as characteristic of this syndrome. Radiographic fndings included shape anomalies of the vertebral bodies such as cuboid-shaped vertebral bodies, mild scoliosis, short and broad tubular bones, brachymetacarpalia, brachymetatarsalia, and brachy-dactyly, lumbar hyperlordosis, generalized osteopenia, and hypoplastic iliac wings. Conclusions: Few cases have been described, as this is a rare skeletal dysplasia. This paper describes a new familial case of SED-BDS. © The American Journal of Case Reports.

Tachycardia-induced cardiomyopathy

Tachycardia-induced cardiomyopathy (TIC) is an important cause of heart failure as it is potentially reversible after ventricular rate control. A 66-year-old hypertensive woman presented with a 15-day history of tachycardia, dyspnoea and oedema. ECG revealed atrial fibrillation with ventricular frequency of 130 beats per minute (bpm). Echocardiogram showed dilated left ventricle (LV) with 0.39 ejection fraction. Angiography revealed non-obstructed coronary arteries. Heart rate and cardiac failure were controlled with amiodarone, digoxine, captopril, metoprolol and furosemide. During follow-up, despite drug dose optimisation, the patient kept complaining of tachycardia and dyspnoea with a ventricular rate between 108 and 120 bpm. Medical staff suspected she was not taking her medicines properly. Two months later, the patient was asymptomatic and had converted to sinus rhythm (heart rate of 76 bpm). Echocardiogram showed normal LV size and function. Patient 's diagnosis was TIC. Although rare, TIC should be considered in all cases of systolic dysfunction associated with tachyarrhythmia. Copyright 2012 BMJ Publishing Group. All rights reserved.

Frequency of multiple endocrine neoplasia type 1 in a group of patients with pituitary adenoma: genetic study and familial screening

The purpose of this study it was to evaluate the frequency of Multiple Endocrine Neoplasia type 1 (MEN1) in patients with pituitary adenoma and to perform genetic analysis and familial screening of those individuals afflicted with MEN1. 144 patients with pituitary adenoma at Botucatu Medical School, UNESP-Univ Estadual Paulista, were assessed retrospectively for MEN1 during the years of 2005-2011. The patients were evaluated for the presence of primary hyperparathyroidism (PHP) and enteropancreatic tumors. Genetic analysis was performed for the individuals with clinically diagnosed MEN1. Thirteen patients met the diagnostic criteria for MEN1, but three individuals belong to the same family and they were considered as a single MEN1 event, revealing 7.7 % frequency of MEN1 in this patient group. Genetic analysis showed MEN1 mutations in four index cases: IVS4+1 G>A, IVS3-6 C>T, c.1547insC and a new D180A mutation. One patient did not agree to participate in the genetic study and another one was referred for follow up in other hospital. Only polymorphisms were found in the other individuals, one of which was novel. We identified a high frequency of MEN1 in pituitary adenoma patients. Since PHP is one of the most common MEN1 tumor and patients are mostly asymptomatic, we suggest that all pituitary adenoma patients have their calcium profile analyzed. © 2013 Springer Science+Business Media New York.

Doxorubicin induced dilated cardiomyopathy in a rabbit model: An update

Dilated cardiomyopathy (DCM) is characterized by chamber dilation and cardiac dysfunction. Because of the poor prognosis, models are needed for the investigation of and development of new therapeutic approaches, as well as stem cell therapy. Doxorubicin (DOX), used as chemotherapeutic agent, is reported to be cumulative cardiotoxic causing DCM. The aim of the study was to investigate the onset of systolic dysfunction using echocardiography in rabbits receiving two different doses of DOX (1. mg/kg twice a week and 2. mg/kg once a week). Twenty rabbits were treated with doxorubicin in two different doses for 6. weeks and compared with a control group treated with NaCl 0.9%. The effect of doxorubicin on the myocardium was investigated with histological analysis and scanning electron microscopy of left ventricle (LV), as well as in the interventricular septum (IVS) and right ventricle (RV). The results showed a high mortality rate for rabbits receiving 2. mg/kg once a week. A significant reduction in systolic function was present in animals treated with DOX after 6. weeks, with decreased ejection fraction and shortening fraction. Histology and electron microscopy revealed vacuolization, intracytoplasmic granulation, necrosis and interstitial fibrosis in LV, as well as in the IVS and RV. Doxorubicin induced changes are present in the LV, RV and IVS, and the administration at the dose of 1. mg/kg twice a week for only 6. weeks is safe and sufficient to induce DCM in rabbits. © 2012 Elsevier Ltd.

Uso da farmacogenética cardiovascular na análise e prevenção de doenças cardiovasculares e classificação em haplogrupos pelo cromossomo Y e DNA mitocondrial

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo moleculares das regiões cromossômicas 18p e 18q proximal em portadores de gagueira persistente da familial

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

O gene PHF21B como candidato a predisposição familia em familial em cânceres de cabeça e pescoço

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Perfil mutacional do gene APC em pacientes com polipose adenomatosa familial no estado do Pará

O câncer colorretal é um grave problema de saúde pública na região norte, sendo a 3a neoplasia mais frequente entre os homens e a 2a entre as mulheres. Cerca de 10% destes tumores são hereditários e a polipose adenomatosa familial está entre as principais causas destes. Mutações no gene APC são responsáveis pelo desenvolvimento de tumores nestes pacientes e estão presentes desde a fase mais precoce na carcinogênese, além disso, existe uma relação entre o tipo de mutação e apresentação clínica da doença. Até o presente momento não existe uma publicação com o perfil de mutação do gene APC na região norte do país. Este trabalho tem como objetivo principal, identificar o perfil de mutações no gene APC em famílias do estado do Pará. Um total de 15 pacientes foi analisado provenientes de cinco famílias, todos atendidos no UNACON do HUJBB. Foi realizado a extração de DNA do sangue periférico e realizado um sequenciamento direto em um membro de cada família, obtendo desta forma um screening molecular e os demais membros da família foram genotipados pela técnica ARMS. A análise estatística foi realizada pelos softwares que acompanham o próprio produto. Neste estudo foram encontrados mutações nos 15 membros estudados (provenientes das 5 famílias), 40% das quais eram do tipo frameshift, 35% silenciadoras e 20% nonsense. Sendo que 60% de todas as mutações ocorreram na região MCR. Entre as três mutações mais frequentes na literatura, neste estudo foram encontradas duas: códon 1309 (em 40% dos indivíduos) e no códon 1061 (em 10% dos indivíduos). Estes números foram bem diferentes dos encontrados na literatura, reforçando o papel da miscigenação na frequência das mutações. A mutação c.3956delC foi a única encontrada em todas as famílias analisadas, o que pode comportar-se como um forte biomarcador desta síndrome. A avaliação clínica dos pacientes confirmou a correlação genótipo/fenótipo, sendo um fator determinante para o direcionamento clínico e aconselhamento genético. A plataforma confeccionada para análise de mutações pela técnica ARMS será de grande utilidade, já que conseguiu detectar mutações no 15 indivíduos estudados a um custo bem inferior que o sequenciamento direto por PCR.

Perfil da fluência: análise comparativa entre gagueira desenvolvimental persistente familial e isolada

PURPOSE: to evaluate and compare the fluency between the familial and the sporadic persistent developmental stuttering, characterizing the typology and the frequency of the disfluencies, the speech rate and the severity of the stuttering. METHOD: 40 participants aged from 6 to 42 years old, divided in two groups with twenty participants in each one: Familial Persistent Developmental Stuttering and Sporadic Persistent Developmental Stuttering. The procedures used were: clinical and familial history, assessment of fluency and Stuttering Severity Instrument. RESULTS: there were no statistically significant differences between the groups regarding the frequency of stuttering like disfluencies, the flow of syllables and words per minute and the severity of stuttering. It was noted a tendency of the group with familial stuttering to show a bigger variability of the severity of stuttering, going from mild to very severe, whereas in the group with sporadic stuttering, the severity varied from mild to severe. CONCLUSION: this study represents the first effort to the characterization of the speech fluency profile of the subgroups of people who stutter, namely familial persistent developmental stuttering and sporadic persistent developmental stuttering. It is possible to conclude that the speech fluency profile of people who stutter, independently of the familial history, is similar. It is noteworthy that the occurrence of some stuttering-like disfluencies, monosyllabic word repetition, block and intrusion were different between groups.

The Role of Lipotoxicity in Smoke Cardiomyopathy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudos moleculares das regiões cromossômicas 7q31 e 7q34 em portadores de gagueira persistente familial

A gagueira é um distúrbio no ritmo da fala no qual o indivíduo sabe precisamente o que quer dizer, mas ao mesmo tempo é incapaz de dizê-lo devido à repetição involuntária, ao prolongamento ou à cessação do som. Este distúrbio da comunicação acomete cerca de 1 a 2 % da população mundial, e esta freqüência varia de acordo com a idade, sendo mais comum em crianças com idade pré-escolar (de 2,4 a 5%); e com o sexo (3 M : 1 F). Desde a década de 50 a gagueira vem sendo estudada por fonoaudiólogos e geneticistas. Vários fatores são tidos na literatura como de risco para o desenvolvimento da gagueira persistente, dentre os quais destacamos: idade, sexo, tipo e tempo de duração das disfluências, outros distúrbios fonoaudiológicos, características secundárias, fatores genéticos, comportamentos familiares e outros. Desta forma, a gagueira não deve ser tratada como uma entidade nosológica única, pois apresenta característica multidimensional e multifatorial. Dentre os principais fatores que sugerem etiologia genética para a gagueira destacamos: 1)Gagueira presente em agregados familiais; 2)Maior probabilidade de se desenvolver em indivíduos consanguíneos; 3)Semelhança dos traços fenotípicos característicos, independente da língua e cultura; 4)Maior concordância entre gêmeos monozigóticos do que em gêmeos dizigóticos. A triagem genômica em famílias de gagos provenientes do Paquistão, e dos Estados Unidos, Suécia e Israel indicaram uma possível ligação da gagueira com o cromossomo 7. O objetivo deste trabalho foi a análise de ligação nas regiões cromossômicas 7q31 e 7q34 através de marcadores microssatélites em 31 famílias brasileiras com gagueira persistente, com mais de um indivíduo gago em idade acima de 6 anos. Utilizou-se para a classificação da gagueira, o SSI aplicado por profissionais especializados nesta disfluência... (Resumo completo, clicar acesso eletrônico abaixo)

Cardiomyopathy and cell therapy: ejection fraction improvement and cardiac muscle mass increasing, after a year of bone marrow stem cells transplantation, by magnetic resonance image

The idiopathic dilated cardiomyopathy (IDC) is one of the major public health problems in the western world. Patients with IDC in functional class IV (New York Health Association - NYHA), even after therapeutic optimization, have high mortality. Stem cell therapy has emerged as a potential therapeutic option for cell death-related heart diseases and several positive effects were assigned to cell therapy in cardiomyopathy. The aim of this study was identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy patients (IDC) who were treated by transplantation of autologous bone marrow mononuclear cells (BMMC). Intracoronary injections of autologous BMMC were performed in eight patients with severe ventricle dysfunction (mean of left ventricle ejection fraction – LEVF=20.03%), cardiac mass muscle around 156.2 g and NYHA between III and IV grades, other 8 IDC patients received placebo. The IDCs were followed - up for one and two years, by magnetic resonance imaging (MRI). The results after one year showed significant improvement in LVEF (mean=181.4) and muscle mass increasing (mean=181.4 g), after two years the LVEF continued improving, reaching a mean of 32.69% and the cardiac muscle mass kept stable (mean=179.4 g). Excepted for one patient, all the other had improvement in the NYHA functional class. The placebo group did not show any improvement. We believe that BMMC implant may be a beneficial therapeutic option for IDC patients.

Perfil da fluência e frequência da gagueira do desenvolvimento persistente familial

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Guidelines for the management and treatment of periodic fever syndromes Familial Mediterranean Fever

To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints; 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene; 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment; 4. The therapy of choice is colchicine; this drug has proven effectiveness in preventing acute inflammatory episodes and progression towards amyloidosis in adults; 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.