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1.
Artigo em Inglês | MEDLINE | ID: mdl-32462550

RESUMO

PURPOSE: The prospective, multicenter SMART SF trial demonstrated the acute safety and effectiveness of the 56-hole porous tip irrigated contact force (CF) catheter for drug-refractory paroxysmal atrial fibrillation (PAF) ablation with a low primary adverse event rate (2.5%), leading to FDA approval of the catheter. Here, we are reporting the long-term effectiveness and safety results that have not yet been reported. METHODS: Ablations were performed using the 56-hole porous tip irrigated CF catheter guided by the 3D mapping system stability module. The primary effectiveness endpoint was freedom from atrial tachyarrhythmia (including atrial fibrillation, atrial tachycardia, and/or atrial flutter), based on electrocardiographic data at 12 months. Atrial tachyarrhythmia recurrence occurring 3 months post procedure, acute procedural failures such as lack of entrance block confirmation of all PVs, and undergoing repeat procedure for atrial fibrillation in the evaluation period (91 to 365 days post the initial ablation procedure) were considered to be effectiveness failures. RESULTS: Seventy-eight patients (age 64.8 ± 9.7 years; male 52.6%; Caucasian 96.2%) participated in the 12-month effectiveness evaluation. Mean follow-up time was 373.5 ± 45.4 days. The Kaplan-Meier estimate of freedom from 12-month atrial tachyarrhythmia was 74.9%. Two procedure-related pericardial effusion events were reported at 92 and 180 days post procedure. There were no pulmonary vein stenosis complications or deaths reported through the 12-month follow-up period. CONCLUSIONS: The SMART SF 12-month follow-up evaluation corroborates the early safety and effectiveness success previously reported for PAF ablation with STSF.

2.
J Card Fail ; 26(2): 151-159, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31634574

RESUMO

BACKGROUND: We compared the relationship between the third heart sound (S3) measured by an implantable cardiac device (devS3) and auscultation (ausS3) and evaluated their prognostic powers for predicting heart failure events (HFEs). METHODS AND RESULTS: In the MultiSENSE study, devS3 was measured daily with continuous values, whereas ausS3 was assessed at study visits with discrete grades. They were compared among patients with and without HFEs at baseline and against each other directly. Cox proportional hazard models were developed between follow-up visits and over the whole study. Simulations were performed on devS3 to match the limitations of auscultation. We studied 900 patients, of whom 106 patients experienced 192 HFEs. Two S3 sensing modalities correlated with each other, but at baseline, only devS3 differentiated patients with or without HFEs (P < 0.0001). The prognostic power of devS3 was superior to that of ausS3 both between follow-up visits (HR = 5.7, P < 0.0001, and 1.7, P = 0.047, respectively) and over the whole study (HR = 2.9, P < 0.0001, and 1.4, P = 0.216, respectively). Simulation results suggested this superiority may be attributed to continuous monitoring and to subaudible measuring capability. CONCLUSIONS: S3 measured by implantable cardiac devices has stronger prognostic power to predict episodes of future HFEs than that of auscultation.

3.
J Neurol ; 266(8): 1919-1926, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069529

RESUMO

BACKGROUND: Neurological disorders are clinically heterogeneous group of disorders and are major causes of disability and death. Several of these disorders are caused due to genetic aberration. A precise and confirmatory diagnosis in the patients in a timely manner is essential for appropriate therapeutic and management strategies. Due to the complexity of the clinical presentations across various neurological disorders, arriving at an accurate diagnosis remains a challenge. METHODS: We sequenced 1012 unrelated patients from India with suspected neurological disorders, using TruSight One panel. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 197 genes in 405 (40%) cases and 178 mutations were novel. The highest diagnostic rate was observed among patients with muscular dystrophy (64%) followed by leukodystrophy and ataxia (43%, each). In our cohort, 26% of the patients who received definitive diagnosis were primarily referred with complex neurological phenotypes with no suggestive diagnosis. In terms of mutations types, 62.8% were truncating and in addition, 13.4% were structural variants, which are also likely to cause loss of function. CONCLUSION: In our study, we observed an improved performance of multi-gene panel testing, with an overall diagnostic yield of 40%. Furthermore, we show that NGS (next-generation sequencing)-based testing is comprehensive and can detect all types of variants including structural variants. It can be considered as a single-platform genetic test for neurological disorders that can provide a swift and definitive diagnosis in a cost-effective manner.


Assuntos
Análise de Dados , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Doenças do Sistema Nervoso/genética , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Índia/epidemiologia , Masculino , Herança Multifatorial/genética , Mutação/genética , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/epidemiologia
4.
Cancer Med ; 7(11): 5439-5447, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30264478

RESUMO

Liquid biopsy is increasingly gaining traction as an alternative to invasive solid tumor biopsies for prognosis, treatment decisions, and disease monitoring. Matched tumor-plasma samples were collected from 180 patients across different cancers with >90% of the samples below Stage IIIB. Tumors were profiled using next-generation sequencing (NGS) or quantitative PCR (qPCR), and the mutation status was queried in the matched plasma using digital platforms such as droplet digital PCR (ddCPR) or NGS for concordance. Tumor-plasma concordance of 82% and 32% was observed in advanced (Stage IIB and above) and early (Stage I to Stage IIA) stage samples, respectively. Interestingly, the overall survival outcomes correlated to presurgical/at-biopsy ctDNA levels. Baseline ctDNA stratified patients into three categories: (a) high ctDNA correlated with poor survival outcome, (b) undetectable ctDNA with good outcome, and (c) low ctDNA whose outcome was ambiguous. ctDNA could be a powerful tool for therapy decisions and patient management in a large number of cancers across a variety of stages.


Assuntos
DNA Tumoral Circulante , Neoplasias/genética , Neoplasias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Adulto Jovem
5.
JACC Clin Electrophysiol ; 4(2): 212-220, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29749940

RESUMO

OBJECTIVES: The goal of this study is to assess the safety and efficacy of mechanical lead extraction utilizing the Evolution system. BACKGROUND: Compared with other techniques commonly used for lead extraction, data regarding the safety and efficacy of mechanical lead extraction using the Evolution system is limited and needs further evaluation. METHODS: Between June 1, 2009 and September 30, 2016, we retrospectively analyzed 400 consecutive patients who exclusively underwent mechanical lead extraction utilizing the Evolution system. RESULTS: A total of 400 patients underwent mechanical lead extraction of 683 leads. Mean age of extracted leads was 6.77 ± 4.42 years (range 1 to 31 years). The extracted device system was an implantable cardioverter-defibrillator in 274 patients (68.5%) and a pacemaker system in 126 patients (31.5%). Complete lead removal rate was 97% with a clinical success rate of 99.75%. Incomplete lead removal with <4-cm remnant was associated with older leads (lead age >8 years). Failure to achieve clinical success was noted in 1 patient (0.25%). Cardiac papillary avulsion, system-related infection, and cardiac tamponade were the major complications noted in 6 patients (1.5%). Minor complications were encountered in 24 patients (6%), of which hematoma requiring evacuation was the most common minor complication. There were no patient deaths. CONCLUSIONS: In our single-center study, lead extractions utilizing the Evolution mechanical lead extraction system were safe and effective and resulted in high clinical and procedural success, with low complication rates and no fatalities.


Assuntos
Desfibriladores Implantáveis/efeitos adversos , Remoção de Dispositivo , Marca-Passo Artificial/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Remoção de Dispositivo/efeitos adversos , Remoção de Dispositivo/métodos , Remoção de Dispositivo/estatística & dados numéricos , Falha de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/cirurgia , Estudos Retrospectivos , Cirurgia Assistida por Computador , Resultado do Tratamento
6.
Breast Cancer Res Treat ; 170(1): 189-196, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29470806

RESUMO

PURPOSE: Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. METHODS: We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2. CONCLUSION: In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Detecção Precoce de Câncer , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Índia/epidemiologia , Programas de Rastreamento , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
7.
Cancer Med ; 6(5): 883-901, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28371134

RESUMO

Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single-nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer-related genes. The tissue-specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin-fixed paraffin-embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced-stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages.


Assuntos
DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Imuno-Histoquímica/métodos , Neoplasias/terapia , Análise de Sequência de DNA/métodos , Linhagem Celular Tumoral , Variações do Número de Cópias de DNA , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , Padrão de Cuidado , Translocação Genética
8.
JACC Heart Fail ; 5(3): 216-225, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28254128

RESUMO

OBJECTIVES: The aim of this study was to develop and validate a device-based diagnostic algorithm to predict heart failure (HF) events. BACKGROUND: HF involves costly hospitalizations with adverse impact on patient outcomes. The authors hypothesized that an algorithm combining a diverse set of implanted device-based sensors chosen to target HF pathophysiology could detect worsening HF. METHODS: The MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) study enrolled patients with investigational chronic ambulatory data collection via implanted cardiac resynchronization therapy defibrillators. HF events (HFEs), defined as HF admissions or unscheduled visits with intravenous treatment, were independently adjudicated. The development cohort of patients was used to construct a composite index and alert algorithm (HeartLogic) combining heart sounds, respiration, thoracic impedance, heart rate, and activity; the test cohort was sequestered for independent validation. The 2 coprimary endpoints were sensitivity to detect HFE >40% and unexplained alert rate <2 alerts per patient-year. RESULTS: Overall, 900 patients (development cohort, n = 500; test cohort, n = 400) were followed for up to 1 year. Coprimary endpoints were evaluated using 320 patient-years of follow-up data and 50 HFEs in the test cohort (72% men; mean age 66.8 ± 10.3 years; New York Heart Association functional class at enrollment: 69% in class II, 25% in class III; mean left ventricular ejection fraction 30.0 ± 11.4%). Both endpoints were significantly exceeded, with sensitivity of 70% (95% confidence interval [CI]: 55.4% to 82.1%) and an unexplained alert rate of 1.47 per patient-year (95% CI: 1.32 to 1.65). The median lead time before HFE was 34.0 days (interquartile range: 19.0 to 66.3 days). CONCLUSIONS: The HeartLogic multisensor index and alert algorithm provides a sensitive and timely predictor of impending HF decompensation. (Evaluation of Multisensor Data in Heart Failure Patients With Implanted Devices [MultiSENSE]; NCT01128166).


Assuntos
Algoritmos , Assistência Ambulatorial/estatística & dados numéricos , Dispositivos de Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca/terapia , Hospitalização/estatística & dados numéricos , Monitorização Ambulatorial , Idoso , Terapia de Ressincronização Cardíaca , Estudos de Coortes , Progressão da Doença , Impedância Elétrica , Exercício Físico , Feminino , Frequência Cardíaca , Ruídos Cardíacos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa Respiratória , Medição de Risco
9.
Mol Vis ; 22: 1036-47, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27582626

RESUMO

PURPOSE: Retinoblastoma (Rb) is the most common primary intraocular cancer of childhood and one of the major causes of blindness in children. India has the highest number of patients with Rb in the world. Mutations in the RB1 gene are the primary cause of Rb, and heterogeneous mutations are distributed throughout the entire length of the gene. Therefore, genetic testing requires screening of the entire gene, which by conventional sequencing is time consuming and expensive. METHODS: In this study, we screened the RB1 gene in the DNA isolated from blood or saliva samples of 50 unrelated patients with Rb using the TruSight Cancer panel. Next-generation sequencing (NGS) was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect germline pathogenic mutations in 66% (33/50) of the cases, 12 of which were novel. We were able to detect all types of mutations, including missense, nonsense, splice site, indel, and structural variants. When we considered bilateral Rb cases only, the mutation detection rate increased to 100% (22/22). In unilateral Rb cases, the mutation detection rate was 30% (6/20). CONCLUSIONS: Our study suggests that NGS-based approaches increase the sensitivity of mutation detection in the RB1 gene, making it fast and cost-effective compared to the conventional tests performed in a reflex-testing mode.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Neoplasias da Retina/genética , Proteínas de Ligação a Retinoblastoma/genética , Retinoblastoma/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Criança , Pré-Escolar , Códon sem Sentido , Estudos de Coortes , Análise Mutacional de DNA , Éxons/genética , Feminino , Genes do Retinoblastoma , Testes Genéticos/métodos , Mutação em Linhagem Germinativa , Humanos , Índia , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Adulto Jovem
10.
J Clin Diagn Res ; 10(4): PD09-10, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27190884

RESUMO

Bochdalek hernia is the most frequent congenital diaphragmatic hernia which occurs due to a defect in the posterior attachment of the diaphragm when there is a failure of closure of the pleuroperitoneal membrane in utero. It rarely presents for the first time in adults. We report one such case of a 23-year-old male patient who presented with an acute abdomen. Chest X-ray showed air under diaphragm and he was taken up for an emergency laparotomy. Intraoperatively an organoaxial volvulus of the stomach was found in a bochdaleks hernia with a focal gangrene of the stomach fundus with perforation and peritonitis. However, there was no breach of pleural cavity. A sleeve resection of the gangrenous portion of the stomach was performed and the diaphragmatic defect was repaired. Patient made an uneventful postoperative recovery. Gastric gangrene with perforation as a manifestation of the adult bochdalek hernia is indeed rare. A concomitant pneumothorax occurs along with this condition which requires an intercostal drainage tube prior to the laparotomy. We report this case for its unique presentation without pneumothorax.

11.
Tex Heart Inst J ; 43(2): 183-5, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27127441

RESUMO

The use of subcutaneous implantable cardioverter-defibrillators is a novel option for preventing arrhythmia-mediated cardiac death in patients who are at risk of endovascular-device infection or in whom venous access is difficult. However, the potential for electromagnetic interference between subcutaneous defibrillators and left ventricular assist devices is largely unknown. We report the case of a 24-year-old man in whom we observed no electromagnetic interference between a subcutaneous implanted cardioverter-defibrillator and a HeartMate II Left Ventricular Assist System, at 3 different pump speeds. To our knowledge, this is the first report of such findings in this circumstance.


Assuntos
Desfibriladores Implantáveis , Coração Auxiliar , Miocardite/terapia , Taquicardia Atrial Ectópica/prevenção & controle , Eletrocardiografia , Fenômenos Eletromagnéticos , Desenho de Equipamento , Seguimentos , Humanos , Masculino , Miocardite/complicações , Miocardite/fisiopatologia , Taquicardia Atrial Ectópica/etiologia , Taquicardia Atrial Ectópica/fisiopatologia , Adulto Jovem
12.
J Hum Genet ; 61(6): 515-22, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26911350

RESUMO

Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer panel, which includes 13 genes strongly associated with risk of inherited BOC. Multi-gene sequencing was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect pathogenic mutations in 51 (36.2%) cases, out of which 19 were novel mutations. When we considered familial breast cancer cases only, the detection rate increased to 52%. When cases were stratified based on age of diagnosis into three categories, ⩽40 years, 40-50 years and >50 years, the detection rates were higher in the first two categories (44.4% and 53.4%, respectively) as compared with the third category, in which it was 26.9%. Our study suggests that next-generation sequencing-based multi-gene panels increase the sensitivity of mutation detection and help in identifying patients with a high risk of developing cancer as compared with sequential tests of individual genes.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Síndrome Hereditária de Câncer de Mama e Ovário/epidemiologia , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Mutação , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Adulto , Idade de Início , Idoso , Neoplasias da Mama/diagnóstico , Variações do Número de Cópias de DNA , Feminino , Deleção de Genes , Duplicação Gênica , Genes BRCA1 , Genes BRCA2 , Testes Genéticos/métodos , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Índia/epidemiologia , Pessoa de Meia-Idade , Taxa de Mutação , Neoplasias Ovarianas/diagnóstico , Prevalência , Adulto Jovem
13.
Tex Heart Inst J ; 42(2): 152-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25873828

RESUMO

Electrophysiologic procedures in the young engender concern about the potential long-term effects of radiation exposure. This concern is manifold if such procedures are contemplated during pregnancy. Catheter ablations in pregnancy are indicated only in the presence of an unstable tachycardia that cannot be controlled by antiarrhythmic agents. This report describes the case of an 18-year-old pregnant woman and our stratagem to minimize irradiation of the mother and the fetus.


Assuntos
Ablação por Cateter/métodos , Feto/efeitos da radiação , Fluoroscopia/métodos , Complicações Cardiovasculares na Gravidez/cirurgia , Taquicardia Supraventricular/cirurgia , Adolescente , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Gravidez , Exposição à Radiação
14.
Biomed Res Int ; 2015: 940864, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25922843

RESUMO

Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes. Sequencing results were analyzed by read mapping and variant calling in genes of interest, followed by their verification and interpretation. Genetic analysis revealed ABCA4 mutations in all of the five unrelated patients. Among these, four patients were found with compound heterozygous mutations and another one had homozygous mutation. All the affected individuals showed signs and symptoms consistent with the disease phenotype. We report two novel ABCA4 mutations in Indian patients with STGD disease, which expands the existing spectrum of disease-causing variants and the understanding of phenotypic and genotypic correlations. Screening for causative mutations in patients with STGD using panel of targeted gene sequencing by NGS would be a cost effective tool, might be helpful in confirming the precise diagnosis, and contributes towards the genetic counselling of asymptomatic carriers and isolated patients.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Genótipo , Degeneração Macular/congênito , Mutação , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adolescente , Adulto , Análise Mutacional de DNA , Feminino , Humanos , Índia , Degeneração Macular/genética , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Masculino , Doença de Stargardt
15.
PLoS Comput Biol ; 8(10): e1002737, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23133345

RESUMO

We describe methods for rapid sequencing of the entire human mitochondrial genome (mtgenome), which involve long-range PCR for specific amplification of the mtgenome, pyrosequencing, quantitative mapping of sequence reads to identify sequence variants and heteroplasmy, as well as de novo sequence assembly. These methods have been used to study 40 publicly available HapMap samples of European (CEU) and African (YRI) ancestry to demonstrate a sequencing error rate <5.63×10(-4), nucleotide diversity of 1.6×10(-3) for CEU and 3.7×10(-3) for YRI, patterns of sequence variation consistent with earlier studies, but a higher rate of heteroplasmy varying between 10% and 50%. These results demonstrate that next-generation sequencing technologies allow interrogation of the mitochondrial genome in greater depth than previously possible which may be of value in biology and medicine.


Assuntos
DNA Mitocondrial/genética , Genoma Mitocondrial/genética , Genômica/métodos , Análise de Sequência de DNA/métodos , Grupo com Ancestrais do Continente Africano/genética , Bases de Dados Genéticas , Grupo com Ancestrais do Continente Europeu/genética , Variação Genética , Projeto HapMap , Humanos , Reação em Cadeia da Polimerase , Alinhamento de Sequência
16.
Tex Heart Inst J ; 38(4): 409-11, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21841870

RESUMO

A 58-year-old man presented with chest pain and tightness and was diagnosed with a Q-wave anterior myocardial infarction. He then developed pulseless ventricular arrhythmias, which were treated with repeated direct-current shocks and intravenous amiodarone. He underwent emergency cardiac catheterization: stents were deployed in the left anterior descending coronary artery and right coronary artery, and an intra-aortic balloon pump was inserted. Severe refractory cardiogenic shock and incessant ventricular arrhythmias compelled us to place a TandemHeart percutaneous left ventricular assist device 4 hours later. The patient's hemodynamic status stabilized, but the arrhythmias persisted for 36 hours. Multiple doses of intravenous amiodarone and lidocaine and multiple external direct-current shocks were all tried, but these measures failed to terminate the life-threatening ventricular arrhythmias. We performed a pharmacologic block of the left stellate ganglion, and this resulted in a return to sinus rhythm after 1 direct-current shock. To our knowledge, this is the 1st patient with refractory ventricular arrhythmias to have been treated with TandemHeart support and left stellate ganglion block.


Assuntos
Infarto Miocárdico de Parede Anterior/complicações , Arritmias Cardíacas/terapia , Bloqueio Nervoso Autônomo , Coração Auxiliar , Choque Cardiogênico/terapia , Gânglio Estrelado/fisiopatologia , Disfunção Ventricular Esquerda/terapia , Angioplastia Coronária com Balão/instrumentação , Infarto Miocárdico de Parede Anterior/diagnóstico , Infarto Miocárdico de Parede Anterior/terapia , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Terapia Combinada , Resistência a Medicamentos , Eletrocardiografia , Hemodinâmica , Humanos , Balão Intra-Aórtico , Masculino , Pessoa de Meia-Idade , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Stents , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda
17.
J Chem Inf Model ; 51(4): 788-806, 2011 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-21446748

RESUMO

Several efficient correspondence graph-based algorithms for determining the maximum common substructure (MCS) of a pair of molecules have been published in the literature. The extension of the problem to three or more molecules is however nontrivial; heuristics used to increase the efficiency in the two-molecule case are either inapplicable to the many-molecule case or do not provide significant speedups. Our specific algorithmic contribution is two-fold. First, we show how the correspondence graph approach for the two-molecule case can be generalized to obtain an algorithm that is guaranteed to find the optimum connected MCS of multiple molecules, and that runs fast on most families of molecules using a new divide-and-conquer strategy that has hitherto not been reported in this context. Second, we provide a characterization of those compound families for which the algorithm might run slowly, along with a heuristic for speeding up computations on these families. We also extend the above algorithm to a heuristic algorithm to find the disconnected MCS of multiple molecules and to an algorithm for clustering molecules into groups, with each group sharing a substantial MCS. Our methods are flexible in that they provide exquisite control on various matching criteria used to define a common substructure.


Assuntos
Algoritmos , Inteligência Artificial , Estrutura Molecular , Reconhecimento Automatizado de Padrão/métodos , Análise por Conglomerados , Análise por Pareamento
18.
J Proteomics Bioinform ; 4(4): 74-82, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27030788

RESUMO

Gastric cancer is the second leading cause of cancer death worldwide, both in men and women. A genomewide gene expression analysis was carried out to identify differentially expressed genes in gastric adenocarcinoma tissues as compared to adjacent normal tissues. We used Agilent's whole human genome oligonucleotide microarray platform representing ~41,000 genes to carry out gene expression analysis. Two-color microarray analysis was employed to directly compare the expression of genes between tumor and normal tissues. Through this approach, we identified several previously known candidate genes along with a number of novel candidate genes in gastric cancer. Testican-1 (SPOCK1) was one of the novel molecules that was 10-fold upregulated in tumors. Using tissue microarrays, we validated the expression of testican-1 by immunohistochemical staining. It was overexpressed in 56% (160/282) of the cases tested. Pathway analysis led to the identification of several networks in which SPOCK1 was among the topmost networks of interacting genes. By gene enrichment analysis, we identified several genes involved in cell adhesion and cell proliferation to be significantly upregulated while those corresponding to metabolic pathways were significantly downregulated. The differentially expressed genes identified in this study are candidate biomarkers for gastric adenoacarcinoma.

20.
Tex Heart Inst J ; 32(2): 220-3, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16107121

RESUMO

Although there have been significant advances in the medical treatment of heart failure patients with impaired systolic function, very little is known about the diagnosis and treatment of diastolic dysfunction. We report the cases of 3 patients in New York Heart Association functional class IV who had echocardiographically documented diastolic dysfunction as the main cause of heart failure. All 3 patients received medical therapy with long-term milrinone infusion.


Assuntos
Cardiotônicos/administração & dosagem , Diástole/fisiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Milrinona/administração & dosagem , Disfunção Ventricular Esquerda/complicações , Adulto , Idoso , Cardiotônicos/uso terapêutico , Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Infusões Intravenosas , Masculino , Milrinona/uso terapêutico , Fatores de Tempo
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