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1.
Pediatr Cardiol ; 44(1): 95-101, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35841405

RESUMO

Single ventricle (SV) cardiac lesions and tetralogy of Fallot (TOF) are both common forms of cyanotic congenital heart disease. With advances in perioperative care and longitudinal follow-up, survival of these patients has dramatically improved and the majority survive to adulthood. This study compares health-related quality of life (HRQoL) of adult SV and TOF patients to each other and the general population. HRQoL of all surviving, non-transplanted SV and TOF patients 21 years of age and older at our institution was assessed with the SF-36 questionnaire via phone. Additional data including demographic parameters and information related to comorbidities and healthcare utilization were also analyzed. Among 81 eligible SV patients and 207 TOF patients, 33 (41%) and 75 (36%) completed the SF-36 phone survey, respectively. The mean age of SV patients was 32 vs. 38 years in the TOF group (p=0.01). SV patients reported more hepatic, pulmonary, and renal comorbidities. TOF patients were more likely to complete advanced degrees and more likely to have children (p=0.03). SV physical functioning scores were worse compared to TOF. In other domains of the SF-36 questionnaire, SV and TOF scores were similar. Compared to the general population, both groups reported worse bodily pain and mental health, but other aspects of psychosocial and general health were comparable. Overall HRQoL is good for both SV and TOF patients through early and mid-adulthood. Some QoL metrics were modestly worse in the SV patients. While these patients may have some physical limitations, psychosocial wellbeing appears preserved.


Assuntos
Cardiopatias Congênitas , Tetralogia de Fallot , Coração Univentricular , Adulto , Criança , Humanos , Qualidade de Vida/psicologia , Cardiopatias Congênitas/cirurgia , Inquéritos e Questionários
2.
J Cell Sci ; 135(17)2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35946425

RESUMO

Mitral and tricuspid valves are essential for unidirectional blood flow in the heart. They are derived from similar cell sources, and yet congenital dysplasia affecting both valves is clinically rare, suggesting the presence of differential regulatory mechanisms underlying their development. Here, we specifically inactivated Dicer1 in the endocardium during cardiogenesis and found that Dicer1 deletion caused congenital mitral valve stenosis and regurgitation, whereas it had no impact on other valves. We showed that hyperplastic mitral valves were caused by abnormal condensation and extracellular matrix (ECM) remodeling. Our single-cell RNA sequencing analysis revealed impaired maturation of mesenchymal cells and abnormal expression of ECM genes in mutant mitral valves. Furthermore, expression of a set of miRNAs that target ECM genes was significantly lower in tricuspid valves compared to mitral valves, consistent with the idea that the miRNAs are differentially required for mitral and tricuspid valve development. We thus reveal miRNA-mediated gene regulation as a novel molecular mechanism that differentially regulates mitral and tricuspid valve development, thereby enhancing our understanding of the non-association of inborn mitral and tricuspid dysplasia observed clinically.


Assuntos
MicroRNAs , Valva Tricúspide , Matriz Extracelular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Valva Mitral , Valva Tricúspide/anormalidades
3.
Biochem Mol Biol Educ ; 48(3): 276-282, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32202695

RESUMO

Biology and biochemistry students must learn to visualize and comprehend the complex three-dimensional (3D) structures of macromolecules such as proteins or DNA. However, most tools available for teaching biomolecular structures typically operate in two dimensions. Here, we present protocols and pedagogical approaches for using immersive augmented reality (AR) visors, specifically the Microsoft HoloLens, to reinforce learning with large scale 3D holographic structures. We developed a novel workflow to render vividly colored custom biomolecules in AR visors. In addition, we developed AR exercises to review concepts relevant to protein or DNA structure and then implemented the exercises in four different biology and biochemistry courses. Surveys showed that students reported greater interest in biomolecular structures after the exercise. We also highlight some of the advantages and disadvantages of the software and hardware of this upcoming technology.


Assuntos
Realidade Aumentada , Bioquímica/educação , Biologia/educação , DNA , Humanos , Imageamento Tridimensional , Aprendizagem , Substâncias Macromoleculares , Conformação Proteica , Proteínas/química , Software , Estudantes
4.
Clin Pediatr (Phila) ; 59(3): 245-251, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31896280

RESUMO

The Adult Congenital and Pediatric Cardiology (ACPC) Section of the American College of Cardiology sought to develop quality indicators/metrics for ambulatory pediatric cardiology practice. The objective of this study was to report the creation of metrics for patients with Kawasaki disease. Over a period of 5 months, 12 pediatric cardiologists developed 24 quality metrics based on the most relevant statements, guidelines, and research studies pertaining to Kawasaki disease. Of the 24 metrics, the 8 metrics deemed the most important, feasible, and valid were sent on to the ACPC for consideration. Seven of the 8 metrics were approved using the RAND method by an expert panel. All 7 metrics approved by the ACPC council were accepted by ACPC membership after an "open comments" process. They have been disseminated to the pediatric cardiology community for implementation by the ACPC Quality Network.


Assuntos
Assistência Ambulatorial/normas , Cardiologia/normas , Síndrome de Linfonodos Mucocutâneos/terapia , Pediatria/normas , Garantia da Qualidade dos Cuidados de Saúde/métodos , Indicadores de Qualidade em Assistência à Saúde , Criança , Humanos , Estados Unidos
5.
World J Pediatr Congenit Heart Surg ; 10(1): 42-49, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30760124

RESUMO

INTRODUCTION: Knowledge gaps exist in the life expectancy and functional outcome of patients with congenitally corrected transposition (ccTGA) presenting early in life, which is relevant in the evaluation of early anatomic repair. METHODS: In a single-center analysis, 91 patients with ccTGA were identified over 25 years, of which 31 presented with biventricular anatomy in the first year of life and formed the study cohort. End points for analysis included survival, moderate or worse tricuspid valve regurgitation, and systemic right ventricle (RV) dysfunction. Median follow-up was 4.9 years (range: 7 days to 20 years). RESULTS: Among 31 patients presenting in the first year of life, 9 (29%) never received cardiac surgery, while 22 (71%) underwent 36 cardiac operations. Overall freedom from moderate or severe systemic RV dysfunction was 75% at 10 years. Overall survival was 82% at 10 years. Surgical mortality was 5.6% (2/36). Among survivors with a systemic RV, 23 (100%) of 23 were Ross or NYHA class I or II at last follow-up. CONCLUSIONS: Congenitally corrected transposition presenting in the first year of life and maintaining a systemic RV can expect (1) long-term survival of more than 80% at 10 years, (2) low expected surgical mortality (overall 6%), and (3) 75% late freedom from major RV dysfunction at 10 years. Pending multi-institutional analyses, this experience with a systemic RV in ccTGA provides an initial benchmark for comparison when considering early elective anatomic correction.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Transplante de Coração/métodos , Transposição dos Grandes Vasos/mortalidade , Transposição das Grandes Artérias Corrigida Congenitamente , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Transposição dos Grandes Vasos/cirurgia , Resultado do Tratamento , Estados Unidos/epidemiologia
6.
J Vet Med Sci ; 81(3): 491-498, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30726784

RESUMO

Postpartum uterine disease due to poor uterine involution continues to be a significant factor that contributes to poor reproductive efficiency in dairy cattle. Therapy that increases the frequency, duration and strength of uterine contractions in the postpartum period might enhance uterine involution, resulting in improved reproductive performance. The objective of this clinical trial was to study the effect of two uterine ecbolic therapies, oxytocin and prostaglandinF2α on uterine involution, postpartum endometritis, and reproductive performance. A randomized double-blinded clinical trial was conducted in 118 dairy cows from two research herds that had normal parturition and expulsion of the fetal membranes. Within 24 hr after calving, cows were randomly assigned to receive intramuscular injections twice a day of 50 IU of oxytocin, or 25 mg of dinoprost (PGF2α) or saline (control) for 7 days. Cows were monitored from day 3 to day 63 ± 3 days postpartum by transrectal palpation of the uterus, vaginoscopy, Metricheck® examination and by endometrial cytology. Blood samples were collected for measurement of progesterone in weeks 3 (21 ± 3 days), 5 (35 ± 3 days), 7 (49 ± 3 days), and 9 (63 ± 3 days) postpartum. Herd breeding records were obtained to determine reproductive performance in all cows. Neither oxytocin nor prostaglandin F2α therapy during the first week postpartum had any significant effect on the rate of uterine involution, prevalence of endometritis or reproductive performance, compared to untreated controls. Ecbolic drugs, as used here, are not recommended for use in clinical practice to improve involution or reproductive tract health in normal cows.


Assuntos
Doenças dos Bovinos/prevenção & controle , Dinoprosta/uso terapêutico , Endometrite/veterinária , Ocitócicos/uso terapêutico , Ocitocina/uso terapêutico , Útero/efeitos dos fármacos , Animais , Bovinos , Colo do Útero/efeitos dos fármacos , Método Duplo-Cego , Endometrite/epidemiologia , Endometrite/prevenção & controle , Feminino , Parto/efeitos dos fármacos , Período Pós-Parto , Prevalência , Progesterona/sangue , Distribuição Aleatória , Saúde Reprodutiva
7.
Circ Genom Precis Med ; 11(10): e000048, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30354301

RESUMO

Girls and women with Turner syndrome face a lifelong struggle with both congenital heart disease and acquired cardiovascular conditions. Bicuspid aortic valve is common, and many have left-sided heart obstructive disease of varying severity, from hypoplastic left-sided heart syndrome to minimal aortic stenosis or coarctation of the aorta. Significant enlargement of the thoracic aorta may progress to catastrophic aortic dissection and rupture. It is becoming increasingly apparent that a variety of other cardiovascular conditions, including early-onset hypertension, ischemic heart disease, and stroke, are the major factors reducing the life span of those with Turner syndrome. The presentations and management of cardiovascular conditions in Turner syndrome differ significantly from the general population. Therefore, an international working group reviewed the available evidence regarding the diagnosis and treatment of cardiovascular diseases in Turner syndrome. It is recognized that the suggestions for clinical practice stated here are only the beginning of a process that must also involve the establishment of quality indicators, structures and processes for implementation, and outcome studies.


Assuntos
Coartação Aórtica , Dissecção Aórtica , Cardiopatias Congênitas , Hipertensão , Síndrome de Turner , American Heart Association , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/patologia , Dissecção Aórtica/fisiopatologia , Dissecção Aórtica/terapia , Coartação Aórtica/diagnóstico , Coartação Aórtica/patologia , Coartação Aórtica/fisiopatologia , Coartação Aórtica/terapia , Valva Aórtica/anormalidades , Valva Aórtica/patologia , Valva Aórtica/fisiopatologia , Doença da Válvula Aórtica Bicúspide , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/terapia , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/fisiopatologia , Doenças das Valvas Cardíacas/terapia , Humanos , Hipertensão/diagnóstico , Hipertensão/patologia , Hipertensão/fisiopatologia , Hipertensão/terapia , Síndrome de Turner/diagnóstico , Síndrome de Turner/patologia , Síndrome de Turner/fisiopatologia , Síndrome de Turner/terapia , Estados Unidos
8.
Can J Vet Res ; 78(1): 72-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24396185

RESUMO

Persistence of the oxytocin receptor (OTR) in the bovine uterus during the first 7 d after calving was investigated by means of immunohistochemical staining. Immunoreactive OTRs were present in different locations in the uterus on almost all days except day 2, when staining was seen only in the endothelium of blood vessels in the endometrium and myometrium. This finding supports the hypothesis that oxytocin may be ecbolic in cows through the 1st week post partum, but further studies are required to assess the receptor functionality during this period.


La persistance de récepteurs pour l'ocytocine (OTR) dans l'utérus bovin durant les 7 premiers jours suivant le vêlage a été examiné par coloration immunohistochimique. Des OTR immuno-réactifs étaient présents dans différentes localisations dans l'utérus à presque tous les jours sauf au jour 2, alors que la coloration ne fut notée que dans l'endothélium des vaisseaux sanguins dans l'endomètre et le myomètre. Cette trouvaille soutient l'hypothèse que l'ocytocine pourrait être ocytocique chez les vaches durant la 1ère semaine post-partum mais des études supplémentaires sont requises pour évaluer la fonctionnalité des récepteurs durant cette période.(Traduit par Docteur Serge Messier).


Assuntos
Bovinos/metabolismo , Parto/fisiologia , Período Pós-Parto/fisiologia , Receptores de Ocitocina/metabolismo , Útero/metabolismo , Animais , Feminino , Imuno-Histoquímica/veterinária , Gravidez
9.
Circulation ; 126(9): 1143-72, 2012 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-22851541

RESUMO

BACKGROUND: The goal of this statement was to review the available literature on surveillance, screening, evaluation, and management strategies and put forward a scientific statement that would comprehensively review the literature and create recommendations to optimize neurodevelopmental outcome in the pediatric congenital heart disease (CHD) population. METHODS AND RESULTS: A writing group appointed by the American Heart Association and American Academy of Pediatrics reviewed the available literature addressing developmental disorder and disability and developmental delay in the CHD population, with specific attention given to surveillance, screening, evaluation, and management strategies. MEDLINE and Google Scholar database searches from 1966 to 2011 were performed for English-language articles cross-referencing CHD with pertinent search terms. The reference lists of identified articles were also searched. The American College of Cardiology/American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. A management algorithm was devised that stratified children with CHD on the basis of established risk factors. For those deemed to be at high risk for developmental disorder or disabilities or for developmental delay, formal, periodic developmental and medical evaluations are recommended. A CHD algorithm for surveillance, screening, evaluation, reevaluation, and management of developmental disorder or disability has been constructed to serve as a supplement to the 2006 American Academy of Pediatrics statement on developmental surveillance and screening. The proposed algorithm is designed to be carried out within the context of the medical home. This scientific statement is meant for medical providers within the medical home who care for patients with CHD. CONCLUSIONS: Children with CHD are at increased risk of developmental disorder or disabilities or developmental delay. Periodic developmental surveillance, screening, evaluation, and reevaluation throughout childhood may enhance identification of significant deficits, allowing for appropriate therapies and education to enhance later academic, behavioral, psychosocial, and adaptive functioning.


Assuntos
Deficiências do Desenvolvimento/etiologia , Gerenciamento Clínico , Cardiopatias Congênitas/complicações , Adolescente , Assistência ao Convalescente , Algoritmos , Dano Encefálico Crônico/diagnóstico , Dano Encefálico Crônico/epidemiologia , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Procedimentos Cirúrgicos Cardíacos , Criança , Comorbidade , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/prevenção & controle , Deficiências do Desenvolvimento/terapia , Diagnóstico Precoce , Doenças Genéticas Inatas/epidemiologia , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/terapia , Visita Domiciliar , Humanos , Recém-Nascido , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/etiologia , Deficiência Intelectual/terapia , Deficiências da Aprendizagem/diagnóstico , Deficiências da Aprendizagem/epidemiologia , Deficiências da Aprendizagem/etiologia , Deficiências da Aprendizagem/terapia , Neuroimagem , Exame Neurológico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/terapia , Prevalência , Qualidade de Vida , Fatores de Risco
10.
Ann Thorac Surg ; 94(1): 299-301, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22735003

RESUMO

A novel technique of valve-sparing aortic root replacement was applied to 2 children younger than 3 years of age with Marfan syndrome and large aortic root aneurysms. Using elements of both the remodeling and reimplantation techniques, circumferential rings from a 20-mm to 22-mm polyester graft provide stabilization at the subannular and sinotubular levels, and bovine pericardial patches create pseudosinuses. Follow-up at 2 years in 1 patient and 7 months in a second patient revealed satisfactory valve function with stable aortic root size.


Assuntos
Aneurisma Aórtico/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Síndrome de Marfan/cirurgia , Pré-Escolar , Humanos , Lactente
11.
Cancer ; 118(7): 1919-24, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21882180

RESUMO

BACKGROUND: The widespread use of anthracycline chemotherapy has contributed to improved outcomes in children with cancer. The most feared complication of the anthracyclines is cardiotoxicity. Routine echocardiographic monitoring typically is used before, during, and after treatment to minimize cardiotoxicity. The ideal use of screening before and during chemotherapy remains uncertain. METHODS: This was a retrospective review of children who were treated at a single cancer treatment center over 5 years. The results of all echocardiograms and related clinical decisions were reviewed. RESULTS: In 356 patients who were identified for review (age range, 3 months to 22 years; mean age, 10 years; median age, 11 years), 991 echocardiograms were reviewed (average, 2.78 echocardiograms per patient; median, 2 echocardiograms per patient; mode, 1; maximum, 11 echocardiograms per patient). Nine abnormal echocardiograms were identified (2.5% of patients and 0.9% of echocardiograms performed). Four echocardiograms were performed during episodes of septic shock, 2 echocardiograms represented false-positive studies after repeat evaluation, and 1 echocardiogram demonstrated mild abnormality of function on the day of surgical resection of a large Wilms tumor. None of the 356 pretreatment echocardiograms altered treatment decisions. In 635 follow-up echocardiograms during treatment, cardiac defects were detected in 2 patients (0.5%). CONCLUSIONS: The routine use of echocardiograms to screen for anthracycline-induced cardiac damage before and during chemotherapy rarely identified significant cardiac damage to impact treatment decisions. Improved screening techniques with better discrimination and predictability are needed. Pediatric Oncology cooperative groups should consider a revision of standard monitoring protocols before and during treatment.


Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Ecocardiografia/métodos , Cardiopatias/induzido quimicamente , Monitorização Fisiológica , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Adulto Jovem
12.
Invest Ophthalmol Vis Sci ; 51(8): 4226-36, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20220052

RESUMO

PURPOSE: To analyze serum cytokine levels in subjects with different stages of AMD and to study the expression of salient cytokines in postmortem eyes with AMD. METHODS: A suspension array system was used to analyze sera (n = 18 to 20/group) from control subjects and those with early AMD (AREDS stage 1), intermediate dry AMD (AREDS stage 3), advanced AMD with geographic atrophy (GA), or neovascular AMD (CNV). Postmortem eyes with AMD or control eyes were examined immunohistochemically for expression of IP-10 and eotaxin (n = 4 to 8/group). RESULTS: Serum eotaxin and IP-10 levels were significantly elevated in all stages of AMD, except for eotaxin levels in neovascular AMD (P < 0.07). The peak of serum IP-10 concentration was at intermediate dry AMD. In donor eyes, IP-10 and eotaxin expressions were increased in the RPE of eyes with early AMD, GA, and CNV. Eotaxin accumulated within the layer of basal linear/laminar deposits in all stages of AMD, while IP-10 was mainly in eyes with GA and CNV. IP-10 was abundant in the connective tissue matrix associated with CNV, and eotaxin was usually present but more focally and with less intense staining. Both IP-10 and eotaxin were expressed by neovascular endothelial cells. Both IP-10 and eotaxin were expressed in the neurosensory retina, but there was no detectable difference in staining between eyes with or without AMD. CONCLUSIONS: IP-10 and eotaxin may be early biomarkers in AMD. The authors hypothesize that the relative balance between levels of IP-10 and eotaxin is critical in regulating the neovascular response.


Assuntos
Biomarcadores/sangue , Quimiocina CCL11/sangue , Quimiocina CXCL10/sangue , Degeneração Macular/sangue , Epitélio Pigmentado da Retina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Quimiocina CCL11/metabolismo , Quimiocina CXCL10/metabolismo , Neovascularização de Coroide/metabolismo , Feminino , Atrofia Geográfica/metabolismo , Humanos , Técnicas Imunoenzimáticas , Degeneração Macular/metabolismo , Masculino
13.
Cardiol Young ; 18(3): 328-36, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18460222

RESUMO

OBJECTIVE: In 1990, Fontan, Kirklin, and colleagues published equations for survival after the so-called "Perfect Fontan" operation. After 1988, we evolved a protocol using an internal or external polytetraflouroethylene tube of 16 to 19 millimetres diameter placed from the inferior caval vein to either the right or left pulmonary artery along with a bidirectional cava-pulmonary connection. The objective of this study was to test the hypothesis that a "perfect" outcome is routinely achievable in the current era when using a standardized surgical procedure. METHODS: Between 1 January, 1988, and 12 December, 2005, 112 patients underwent the Fontan procedure using an internal or external polytetraflouroethylene tube plus a bidirectional cava-pulmonary connection, the latter usually having been constructed as a previous procedure. This constituted 45% of our overall experience in constructing the Fontan circulation between 1988 and 1996, and 96% of the experience between 1996 and 2005. Among all surviving patients, the median follow-up was 7.3 years. We calculated the expected survival for an optimal candidate, given from the initial equations, and compared this to our entire experience in constructing the Fontan circulation. RESULTS: An internal tube was utilized in 61 patients, 97% of whom were operated prior to 1998, and an external tube in 51 patients, the latter accounting for 95% of all operations since 1999. At 1, 5, 10 and 15 years, survival of the entire cohort receiving polytetraflouroethylene tubes is superimposable on the curve calculated for a "perfect" outcome. Freedom from replacement or revision of the tube was 97% at 10 years. CONCLUSION: Using a standardized operative procedure, combining a bidirectional cavopulmonary connection with a polytetraflouroethylene tube placed from the inferior caval vein to the pulmonary arteries for nearly all patients with functionally univentricular hearts, early and late survival within the "perfect" outcome as predicted by the initial equations of Fontan and Kirklin is routinely achievable in the current era. The need for late revision or replacement of the tube is rare.


Assuntos
Técnica de Fontan , Técnica de Fontan/instrumentação , Técnica de Fontan/métodos , Técnica de Fontan/mortalidade , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/cirurgia , Humanos , Análise Multivariada , Politetrafluoretileno , Reoperação , Resultado do Tratamento
14.
Cloning Stem Cells ; 9(1): 118-29, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17386019

RESUMO

Animal models have played an important part in establishing our knowledge base on reproduction, development, and the occurrence and impact of chromosome abnormalities. Translocations involving the X chromosome and an autosome are unique in that they elicit sex-dependent infertility, with male carriers rendered sterile by synaptic anomalies during meiosis, whereas female carriers conceive but repeatedly abort. Until now the limited access to relevant fetal oocytes has precluded direct study of meiotic events in female carriers. Because somatic cell nuclear transfer (SCNT) circumvents meiotic problems associated with fertility disturbances in translocation carriers, we used SCNT to generate embryos, fetuses, and calves from a cell line derived from a deceased subfertile X-autosome translocation carrier cow to study the meiotic configurations in carrier oocytes. Data from 33 replicates involving 2470 oocyte-donor-cell complexes were assessed for blastocyst development and of these, 42 blastocysts were transferred to 21 recipients. Fourteen pregnancies were detected on day 35 of gestation. One of these was sacrificed for ovary retrieval on day 94 and three went to term. Features of oocytes from the fetal ovary and from the newborn ovaries were examined. Of the pachytene spreads analyzed, 16%, 82%, and 1.5% exhibited quadrivalent, trivalent/univalent, and bivalent/univalent/univalent structures, respectively, whereas among the diakinesis/metaphase I spreads, 16% ring, 75% chain, and 8.3% bivalent/bivalent configurations were noted, suggesting that the low fertility among female carriers may be related to synaptic errors in a predominant proportion of oocytes. Our results indicate that fibroblasts carrying the X-autosome translocation can be used for SCNT to produce embryos, fetuses, and newborn clones to study such basic aspects of development as meiosis and to generate carriers that cannot easily be reproduced by conventional breeding.


Assuntos
Doenças dos Bovinos , Doenças Genéticas Ligadas ao Cromossomo X , Infertilidade Feminina , Meiose , Modelos Biológicos , Técnicas de Transferência Nuclear , Aberrações dos Cromossomos Sexuais , Animais , Bovinos , Doenças dos Bovinos/genética , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/genética , Infertilidade Feminina/genética , Infertilidade Feminina/veterinária , Gravidez , Aberrações dos Cromossomos Sexuais/veterinária
15.
Can Vet J ; 46(3): 255-9, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15884649

RESUMO

This study compares cytobrush and lavage techniques for the assessment of endometrial cytology (EC) in clinically normal postpartum dairy cows. The EC samples were collected from Holstein cows (n = 35) during visit 1 (V1) at 20 to 33 d in milk (DIM) and 2 wk later during visit 2 (V2) at 34 to 47 DIM by using both techniques. A minimum of 100 cells were counted to determine the percentage of cells that were neutrophils (%PMN). The mean %PMN was significantly different between the techniques at V1 (P = 0.001), but not at V2 (P = 0.474). Overall, the %PM N decreased with time postpartum (r2 = 0.36; P = 0.001), but not within V1 (P > 0.05) or V2 (P > 0.1). Uterine diameter was negatively correlated with fluid recovery by the lavage technique (r2 = 0.41; P = 0.002). The mean %PMN was not influenced by the volume of fluid recovered in successful attempts, but 17% (12/70) of attempts yielded no fluid. In conclusion, the cytobrush technique is a consistent and reliable method for obtaining endometrial samples for cystologic examination from postpartum dairy cows.


Assuntos
Doenças dos Bovinos/diagnóstico , Citodiagnóstico/veterinária , Endometrite/veterinária , Transtornos Puerperais/veterinária , Irrigação Terapêutica/veterinária , Animais , Bovinos , Doenças dos Bovinos/patologia , Endometrite/diagnóstico , Endometrite/patologia , Endométrio/citologia , Endométrio/patologia , Feminino , Contagem de Leucócitos/veterinária , Neutrófilos , Período Pós-Parto , Gravidez , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/patologia , Irrigação Terapêutica/instrumentação , Irrigação Terapêutica/métodos
16.
N Engl J Med ; 352(4): 362-72, 2005 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-15673802

RESUMO

BACKGROUND: Unexplained left ventricular hypertrophy often prompts the diagnosis of hypertrophic cardiomyopathy, a sarcomere-protein gene disorder. Because mutations in the gene for AMP-activated protein kinase gamma2 (PRKAG2) cause an accumulation of cardiac glycogen and left ventricular hypertrophy that mimics hypertrophic cardiomyopathy, we hypothesized that hypertrophic cardiomyopathy might also be clinically misdiagnosed in patients with other mutations in genes regulating glycogen metabolism. METHODS: Genetic analyses performed in 75 consecutive unrelated patients with hypertrophic cardiomyopathy detected 40 sarcomere-protein mutations. In the remaining 35 patients, PRKAG2, lysosome-associated membrane protein 2 (LAMP2), alpha-galactosidase (GLA), and acid alpha-1,4-glucosidase (GAA) genes were studied. RESULTS: Gene defects causing Fabry's disease (GLA) and Pompe's disease (GAA) were not found, but two LAMP2 and one PRKAG2 mutations were identified in probands with prominent hypertrophy and electrophysiological abnormalities. These results prompted the study of two additional, independent series of patients. Genetic analyses of 20 subjects with massive hypertrophy (left ventricular wall thickness, > or =30 mm) but without electrophysiological abnormalities revealed mutations in neither LAMP2 nor PRKAG2. Genetic analyses of 24 subjects with increased left ventricular wall thickness and electrocardiograms suggesting ventricular preexcitation revealed four LAMP2 and seven PRKAG2 mutations. Clinical features associated with defects in LAMP2 included male sex, severe hypertrophy, early onset (at 8 to 17 years of age), ventricular preexcitation, and asymptomatic elevations of two serum proteins. CONCLUSIONS: LAMP2 mutations typically cause multisystem glycogen-storage disease (Danon's disease) but can also present as a primary cardiomyopathy. The glycogen-storage cardiomyopathy produced by LAMP2 or PRKAG2 mutations resembles hypertrophic cardiomyopathy but is distinguished by electrophysiological abnormalities, particularly ventricular preexcitation.


Assuntos
Antígenos CD/genética , Cardiomiopatia Hipertrófica/genética , Doença de Depósito de Glicogênio/complicações , Complexos Multienzimáticos/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Quinases Ativadas por AMP , Adolescente , Adulto , Idoso , Algoritmos , Cardiomiopatia Hipertrófica/etiologia , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Criança , Diagnóstico Diferencial , Eletrocardiografia , Doença de Fabry/genética , Feminino , Glicogênio/metabolismo , Doença de Depósito de Glicogênio/diagnóstico , Doença de Depósito de Glicogênio/genética , Doença de Depósito de Glicogênio Tipo II/complicações , Doença de Depósito de Glicogênio Tipo II/genética , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Proteína 2 de Membrana Associada ao Lisossomo , Proteínas de Membrana Lisossomal , Masculino , Pessoa de Meia-Idade , Mutação , Miocárdio/patologia , Linhagem
17.
Pediatr Res ; 53(5): 744-8, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12621127

RESUMO

Previous studies have identified mutations in five ion channel genes as a cause of long QT syndrome, a heterogeneous disorder characterized by prolongation of the QT interval, multiform ventricular tachycardia (torsades de pointes), seizures, syncope, and sudden death. However, in these studies, the average age of initial symptoms is in the third decade of life or later, and few reports have described the genetic causes of long QT syndrome presenting in the prenatal or neonatal period. We used a candidate gene approach to identify the genetic cause of long QT syndrome in an infant whose initial manifestations were detected in utero. Direct bidirectional sequencing of long QT syndrome genes identified a previously unreported HERG missense mutation (R752Q). Three asymptomatic family members were heterozygous for R752Q, and the proband, who manifested ventricular tachycardia in utero, was homozygous. R752Q was not found in 100 normal unrelated chromosomes. Paternal DNA was unavailable for testing. Transient transfection of HERG generated robust IKr, but no current was observed for the mutant HERG. The HERG mutant, R752Q, is associated with a mild phenotype, inasmuch as family members with a heterozygous mutation appear unaffected. The homozygous mutation results in absence of functional IKr, causing a profound loss of HERG channel function, creating the equivalent of a "HERG knockout" and leading to a severe phenotype.


Assuntos
Proteínas de Transporte de Cátions , Proteínas de Ligação a DNA , Síndrome do QT Longo/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana , Canais de Potássio/genética , Transativadores , Sequência de Bases , Canal de Potássio ERG1 , Eletrocardiografia , Canais de Potássio Éter-A-Go-Go , Saúde da Família , Feminino , Homozigoto , Humanos , Recém-Nascido , Síndrome do QT Longo/fisiopatologia , Masculino , Potenciais da Membrana , Dados de Sequência Molecular , Linhagem , Fenótipo , Índice de Gravidade de Doença , Regulador Transcricional ERG
18.
Ann Thorac Surg ; 74(5): 1700-2, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12440639

RESUMO

Pulmonary vasospasm and hypertension may occur after repair or palliation of congenital cardiac defects, and can be fatal in spite of conventional treatment. Nitric oxide has been shown to improve pulmonary hypertension unresponsive to conventional measures after a variety of repairs, but use has infrequently been reported after palliative systemic to pulmonary artery shunts. We report a case of pulmonary hypertension and life threatening desaturation after a modified Blalock-Taussig shunt that responded rapidly to inhaled nitric oxide. Clinical use, further study, and prospective analysis of prophylactic use of nitric oxide appear warranted.


Assuntos
Anomalias dos Vasos Coronários/cirurgia , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico/administração & dosagem , Complicações Pós-Operatórias/tratamento farmacológico , Artéria Pulmonar/cirurgia , Tetralogia de Fallot/cirurgia , Vasoconstrição/efeitos dos fármacos , Administração por Inalação , Feminino , Humanos , Lactente , Cuidados Paliativos , Artéria Pulmonar/efeitos dos fármacos , Artéria Subclávia/cirurgia
19.
J Dairy Sci ; 85(6): 1416-26, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12146472

RESUMO

The objective of this study was to investigate parenteral vitamin E for the prevention of peripartum disease in dairy cows. A randomized clinical trial was conducted in 21 commercial dairy herds. Cows (n = 1142) were randomly assigned to receive either a single subcutaneous injection of 3000 IU of vitamin E, or placebo, 1 wk before expected calving. Serum alpha-tocopherol was significantly increased in treated cows at 7 and 14 d, but not at 21 d after injection. Overall, there were no significant differences between treatment groups in the incidence of retained placenta, clinical mastitis, metritis, endometritis, ketosis, displaced abomasum, or lameness. However, there was a conditional benefit of treatment for reduction of the incidence of retained placenta. Cows with marginal pretreatment vitamin E status (serum alpha-tocopherol to cholesterol mass ratio < 2.5 x 10(-3)) that received an injection of vitamin E tended to have reduced risk of retained placenta. However, in cows with adequate serum vitamin E, there was no reduction in the incidence of any disease. For clinical application, primiparous animals were most likely to benefit from prepartum injection of vitamin E.


Assuntos
Antioxidantes/uso terapêutico , Doenças dos Bovinos/prevenção & controle , Placenta Retida/veterinária , Transtornos Puerperais/veterinária , Vitamina E/uso terapêutico , alfa-Tocoferol/sangue , Animais , Antioxidantes/administração & dosagem , Bovinos , Doenças dos Bovinos/epidemiologia , Endometrite/epidemiologia , Endometrite/prevenção & controle , Endometrite/veterinária , Feminino , Nível de Saúde , Incidência , Injeções Subcutâneas/veterinária , Modelos Logísticos , Mastite Bovina/epidemiologia , Mastite Bovina/prevenção & controle , Paridade , Placenta Retida/epidemiologia , Placenta Retida/prevenção & controle , Período Pós-Parto , Gravidez , Transtornos Puerperais/epidemiologia , Transtornos Puerperais/prevenção & controle , Vitamina E/administração & dosagem
20.
J Res Natl Bur Stand (1977) ; 90(4): 295-303, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-34566157

RESUMO

To obtain reliable thermodynamic data on substituted triazines, it is necessary to use a calorimeter that is capable of high precision with small quantities of sample and in which a homogeneous solution of the corrosive combustion products can be maintained. The enthalpies of combustion of six substituted triazines have been determined in a platinum-lined adiabatic rotating bomb calorimeter. These are the first determinations of enthalpies of combustion or formation to have been reported for these compounds. The values derived for the enthalpies of formation in kJ/mol at 25 °C are as Follows: 2,4,6-trimethoxy-l,3,5-triazine, - 478.60± 0.87; 2,4,6-triethozy- 1,3,5-triazine, - 584.99± 1.50; 2,4,6-tris(2-fluoro-2,2-dinitroethoxy)-l,3,5-triazine, -1109.80±l.53; 2,4-dimethoxy-6-(2-fluoro-2,2-dimtroethoxy)-l,3,5-triazine, -697.08± 1,15; 2-methoxy- 4,6-bis(2-fluoro-2,2-dinitroethoxy)-l,3,5-triazine, -907.71± 2.40; 2-amino-4,6-bis(2-fluoro-2,2-dinitroethoxy)-l,3,5-triazine, - 773-12±1.50.

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