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1.
Sci Rep ; 12(1): 2791, 2022 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-35181675

RESUMEN

Hip osteoarthritis (OA) is characterized by chronic pain, but there remains a mismatch between symptoms and radiological findings. Recently, brain connectivity has been implicated in the modulation of chronic peripheral pain, however its association with perceived pain in hip OA is not understood. We used resting-state functional magnetic resonance imaging (fMRI) to examine functional connectivity associated with pain in hip OA patients. Thirty participants with hip OA and 10 non-OA controls were recruited. Using the visual analogue scale (VAS), pain scores were obtained before and after performing a painful hip activity. All participants underwent 3.0 T resting-state fMRI, and functional connectivity of brain regions associated with pain was determined and compared between participants, and before and after hip activity. Relative to controls, functional connectivity between the secondary somatosensory cortex and left posterior insula was increased, and functional connectivity between the bilateral posterior insula and motor cortices was significantly decreased in hip OA participants. In response to painful hip activity, functional connectivity increased between the thalamus, periaqueductal grey matter and brainstem. Functional connections between brain regions associated with pain are altered in hip OA patients, and several connections are modulated by performing painful activity. Unique lateralization of left posterior insula and linked brain functional connectivity patterns allows assessment of pain perception in hip OA providing an unbiased method to evaluate pain perception and pain modulation strategies.


Asunto(s)
Encéfalo/fisiopatología , Dolor Crónico/fisiopatología , Osteoartritis de la Cadera/fisiopatología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Dolor Crónico/diagnóstico por imagen , Dolor Crónico/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteoartritis de la Cadera/complicaciones , Osteoartritis de la Cadera/diagnóstico por imagen , Dimensión del Dolor , Percepción del Dolor/fisiología , Descanso/fisiología
2.
Clin Biochem ; 50(4-5): 194-205, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27871894

RESUMEN

OBJECTIVE: Meningioma is the most common brain tumor. Genetic mutations in meningioma that include deletion of the neurofibromatosis type 2 gene, (NF2), offer diagnostic information on tumor behavior, recurrence and potential response to treatment. Obtaining high-grade genetic material is critical for accurate, sensitive and robust molecular testing. Currently, no standardized procedure exists for extracting gDNA from meningioma, and this problem was addressed in this report. METHOD: This study compared the yield and quality of extracted gDNA from patient meningioma specimens using an optimized phenol chloroform method and two commercial silica column-based extractions kits and tested respective performances as template in qPCR tests and multiplex ligation-dependent probe amplification (MLPA) NF2 screening. RESULTS: Mean gDNA yields were comparable for each method tested; however, phenol chloroform extraction outperformed column-based kits in all other quality assurance metrics examined. Phenol chloroform extracted gDNA was highly pure, and of a higher fragment size species when compared to column prepared gDNA. qPCR of GAPDH, B2MG, and RPL37A housekeeping genes demonstrated variance in cycle thresholds between patient samples was much lower in the phenol chloroform group. Similarly, primer efficiencies were significantly improved in this sample group which translated to a broader qPCR linear dynamic range and much improved qPCR performance at low concentrations of template. MLPA screening identified NF2 gene deletions in 6 of 12 meningioma samples. Inconsistencies in copy number data for NF2 and reference regions of the genome were observed between gDNA sample extraction groups that included both false negative and positive errors in silica column derived gDNA samples. CONCLUSIONS: This study outlines a highly robust phenol chloroform extraction method for obtaining high-quality gDNA from frozen meningioma tissue and highlights the significance of performing adequate quality assurance when using gDNA for downstream genetic analysis. Most importantly, we demonstrate using gDNA extracted with silica column based kits can lead to diagnostic errors when screening NF2 deletions in meningiomas with MLPA.


Asunto(s)
Análisis Mutacional de ADN/métodos , ADN de Neoplasias/aislamiento & purificación , Neoplasias Meníngeas/genética , Meningioma/genética , Adulto , Anciano , Criopreservación , ADN de Neoplasias/genética , Femenino , Genoma Humano , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular , Mejoramiento de la Calidad , Reacción en Cadena en Tiempo Real de la Polimerasa
3.
Ultrasound Obstet Gynecol ; 37(3): 310-6, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20882562

RESUMEN

OBJECTIVES: To compare the prevalence of previously undiagnosed cardiac structural abnormalities in pregnant women with normal- and high-resistance midtrimester uterine artery Doppler indices. METHODS: Maternal transthoracic echocardiography was undertaken in asymptomatic pregnant women after uterine artery Doppler screening for pre-eclampsia at 21-23 weeks' gestation. Women with a mean uterine artery pulsatility index above the 90(th) centile (1.25) for the local population (multiethnic, socially diverse and migrant) were considered to have high-resistance uteroplacental blood flow indices. The prevalence of newly diagnosed cardiac structural defects in these women was recorded. RESULTS: A total of 491 women underwent echocardiography, of whom 205 had high-resistance uterine artery blood flow indices. There were nine previously undiagnosed, functionally significant cardiac defects in the high-resistance uterine artery blood flow group and only one, functionally insignificant cardiac defect in the normal-resistance group (P = 0.005; relative risk = 12.6, 95% confidence interval, 1.60-98.34). Multiple regression analysis demonstrated that both uterine artery Doppler indices (P = 0.024) and ethnicity (P = 0.048) contributed independently towards a higher prevalence of cardiac defects. CONCLUSIONS: The prevalence of previously undiagnosed maternal cardiac structural abnormalities is significantly increased in women with high midtrimester uterine artery Doppler resistance indices. This observation has important consequences for the current and long-term medical care provided to these patients. Detailed maternal cardiac assessment with echocardiography may be required in migrant women with high uterine artery Doppler indices.


Asunto(s)
Preeclampsia/diagnóstico por imagen , Complicaciones Cardiovasculares del Embarazo/diagnóstico por imagen , Arteria Uterina/diagnóstico por imagen , Útero/diagnóstico por imagen , Resistencia Vascular/fisiología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Tamizaje Masivo , Preeclampsia/epidemiología , Preeclampsia/fisiopatología , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Segundo Trimestre del Embarazo , Prevalencia , Estudios Prospectivos , Ultrasonografía Prenatal , Arteria Uterina/fisiopatología , Útero/irrigación sanguínea , Útero/fisiología
4.
Neth Heart J ; 18(12): 574-82, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21301619

RESUMEN

BACKGROUND: Mechanical dyssynchrony has proven to be superior to QRS duration in predicting response to cardiac resynchronisation therapy (CRT). Whether time to peak longitudinal strain delay between the mid-septum and mid-lateral left ventricular wall better predicts CRT response than tissue Doppler imaging (TDI) is unclear. This study compares the value of the two methods for the assessment of mechanical dyssynchrony and prediction of CRT responders. METHODS: 66 clinical responders and 17 nonresponders to CRT with severe systolic heart failure (LVEF <35%), New York Heart Association classification III or IV and a wide QRS >130 ms with left bundle branch block were evaluated by peak longitudinal strain and TDI. Doppler echocardiograms and electromechanical time delay (EMD) intervals were acquired before and after pacemaker implantation. RESULTS: In all responders EMD measured by peak longitudinal strain was >60 ms before implantation, compared with 76% of the patients measured by TDI. Nonresponders had EMD <60 ms measured by both techniques. Only peak longitudinal strain delay showed shortened values in every responder postimplantation and demonstrated the most significant reduction and could predict responders to CRT. However, EMD measured by TDI did not diminish in 30% of the positive clinical responders. Nonresponders showed worsening of the EMD with peak longitudinal strain, but not with TDI. CONCLUSIONS: Responders to CRT can be excellently predicted if EMD before implantation determined by peak longitudinal strain delay is >60 ms. Peak longitudinal strain delay appears to be superior to TDI to predict the response to CRT. (Neth Heart J 2010;18:574-82.).

5.
Heart ; 95(19): 1561-6, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19224905

RESUMEN

Use of echocardiography has dramatically changed the way in which patients with Marfan syndrome are diagnosed, monitored and treated. Owing to the lethal nature of aortic complications, priority has been given to the assessment of the aortic root. Echocardiographic studies on patients with Marfan syndrome have also provided data supporting primary myocardial involvement, although this evidence has remained controversial for several years. Use of more sensitive ultrasound techniques has demonstrated mild myocardial impairment in these patients. Biventricular function assessment should be added to the aortic root evaluation, so that appropriate treatment may be offered to support myocardial function.


Asunto(s)
Cardiomiopatías/diagnóstico por imagen , Ecocardiografía/métodos , Síndrome de Marfan/diagnóstico por imagen , Adolescente , Adulto , Arritmias Cardíacas/diagnóstico por imagen , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/etiología , Arritmias Cardíacas/terapia , Cardiomiopatías/etiología , Niño , Humanos , Síndrome de Marfan/complicaciones , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/terapia , Disfunción Ventricular Derecha/epidemiología , Disfunción Ventricular Derecha/terapia
6.
Heart ; 94(2): e3, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17916666

RESUMEN

BACKGROUND: A non-invasive method to detect the presence of cardiac allograft vasculopathy (CAV) remains an important goal in clinical cardiology. OBJECTIVE: To assess the value of quantitative dobutamine stress echocardiography (DSE) for the early detection of CAV. METHODS: 42 heart transplant recipients underwent DSE with acquisition of both conventional two-dimensional and colour tissue Doppler data. All studies were analysed conventionally and quantitatively using regional deformation parameters-that is, peak systolic longitudinal strain (in(peak sys)), strain rate (SR(peak sys)) and post-systolic strain index. Myocardial segments were classified as normal, mildly abnormal or severely abnormal based on correlative angiographic findings. RESULTS: At baseline, in(peak sys) was significantly lower in severely abnormal segments than in normal ones. However, at peak stress, in(peak sys) was able to separate three groups of segments. Receiver operating characteristic analysis showed an SR(peak sys) response of <0.5/s to identify patients with CAV with a sensitivity of 88%, specificity of 85% and a negative predictive value of 92%. CONCLUSION: Regional myocardial function is impaired in heart transplant recipients with CAV even when the disease is considered to be non-significant on conventional angiography. Systolic deformation parameters tended to detect the existence of CAV more accurately than conventional visual DSE assessment. Strain rate imaging during stress can therefore safely be used as a non-invasive screening test for detecting CAV in heart transplant recipients.


Asunto(s)
Ecocardiografía de Estrés/normas , Oclusión de Injerto Vascular/diagnóstico por imagen , Trasplante de Corazón , Falla de Prótesis , Adolescente , Adulto , Anciano , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trasplante Homólogo
7.
Heart ; 94(8): 1058-64, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17984214

RESUMEN

BACKGROUND: In normal subjects, systolic longitudinal regional velocity profiles (SVP) (measured both based on pulsed or tissue Doppler) have a non-uniform pattern. SVP from the right ventricle (RV), the septal (Sep) and the inferior wall are similar in shape and tend to be monophasic. Their shape differs markedly from the lateral wall (LW), the posterior wall and the anterior wall, which are biphasic. We studied the hypothesis that the double-peaked SVP in the left ventricular free walls are caused by interventricular interaction. This might have additional implication in understanding the measurements of the timing of SVP maxima in pathology as, for example, used to determine intraventricular dyssynchrony in heart failure. METHODS: 38 healthy individuals underwent a standard echo examination and a tissue Doppler study. SVP from the RV, Sep and LW basal segments were acquired in an apical four-chamber view. The amplitude and timing of the peak velocities were measured. If a double peak was present, the amplitude and timing of the dip was calculated. RESULTS: RV and Sep had a single systolic velocity peak, while the LW had two peaks with a clear dip between both peaks. The first peak in the LW was the earliest event in the cycle (119 (19) ms) followed by the peak Sep (123 (20) ms; p = 0.34). Peak RV velocity occurred at the same time as the dip in the LW (200 (30) vs 203 (30) ms, respectively; p = 0.53). CONCLUSION: Our study suggests that the biphasic SVP in the free walls is probably caused by interventricular interaction. Therefore the timing of maxima on SVP should be used with great caution when looking for intraventricular dyssynchrony as the peaks are influenced by RV function.


Asunto(s)
Función Ventricular Izquierda/fisiología , Adulto , Envejecimiento/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Ecocardiografía Doppler en Color/métodos , Femenino , Tabiques Cardíacos/fisiología , Humanos , Masculino , Persona de Mediana Edad , Mecánica Respiratoria/fisiología , Sístole/fisiología , Función Ventricular Derecha/fisiología
8.
Genes Brain Behav ; 6(8): 750-5, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17331106

RESUMEN

Photosensitive seizures occur most commonly in childhood and adolescence, usually as a manifestation of complex idiopathic generalized epilepsies (IGEs). Molecular mechanisms underlying this condition are yet to be determined because no susceptibility genes have been identified. The NEDD4-2 (Neuronally Expressed Developmentally Downregulated 4) gene encodes a ubiquitin protein ligase proposed to regulate cell surface levels of several ion channels, receptors and transporters involved in regulating neuronal excitability, including voltage-gated sodium channels (VGSCs), the most clinically relevant of the epilepsy genes. The regulation of NEDD4-2 in vivo involves complex interactions with accessory proteins in a cell type specific manner. We screened NEDD4-2 for mutations in a cohort of 253 families with IGEs. We identified three NEDD4-2 missense changes in highly conserved residues; S233L, E271A and H515P in families with photosensitive generalized epilepsy. The NEDD4-2 variants were as effective as wild-type NEDD4-2 in downregulating the VGSC subtype Na(v)1.2 when assessed in the Xenopus oocyte heterologous expression system showing that the direct interaction with the ion channel was not altered by these variants. These data raise the possibility that photosensitive epilepsy may arise from defective interaction of NEDD4-2 with as yet unidentified accessory or target proteins.


Asunto(s)
Epilepsia Generalizada/genética , Epilepsia Refleja/genética , Activación del Canal Iónico/genética , Ubiquitina-Proteína Ligasas/genética , Estudios de Casos y Controles , Cromosomas Humanos Par 18/genética , Estudios de Cohortes , Complejos de Clasificación Endosomal Requeridos para el Transporte , Epilepsia Generalizada/metabolismo , Epilepsia Refleja/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Humanos , Activación del Canal Iónico/fisiología , Masculino , Mutación Missense , Ubiquitina-Proteína Ligasas Nedd4 , Linaje , Eliminación de Secuencia , Homología de Secuencia de Aminoácido , Canales de Sodio/metabolismo , Proteínas de Xenopus
9.
West Afr J Med ; 25(3): 174-8, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17191414

RESUMEN

OBJECTIVE: To determine if intraoperative magnetic resonance imaging improves surgical resection and postoperative outcome of intracranial meningioma. STUDY DESIGN: Prospective, non-randomized, cohort study. METHOD: Intraoperative Magnetic Resonance Imaging (iMRI) was used to evaluate patients with meningioma undergoing surgery. Images were obtained after induction of anaesthesia and at various stages of tumour resection. Extent of surgical resection was graded using Simpson grading system for meningioma. The images were reviewed together with histopathology and early outcome. Primary outcome measure was determined by finding unexpected tumur in interdissection images. Secondary outcome measures were determined by postoperative complications including infections and mortalities. RESULTS: There were 39 procedures in 38 patients from January 1998 to December 2002. Surgical-planning images helped to optimize craniotomy placement. Interdissection images revealed unexpected residual tumour in only 1 patient. Complete resection (Simpson grades 1-3) was achieved in 33 procedures. The average follow up period was 16.4 months. Tumour recurrence has been observed in three patients. Two of these patients had anaplastic meningioma. There was no mortality in the 30-day postoperative period. CONCLUSION: Intraoperative MRI was beneficial in siting the craniotomy in addition to providing anatomical relationships between the tumour and adjacent structures in lesions located at the skull base though the full benefit of these is yet to be determined. The low morbidity and zero mortality recorded in the study may be related to all these factors.


Asunto(s)
Imagen por Resonancia Magnética , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Cirugía Asistida por Computador , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Resultado del Tratamiento
10.
Eur J Echocardiogr ; 7(3): 199-208, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16054869

RESUMEN

AIMS: There are no data on the use of Myocardial Velocity Imaging (MVI) to study the left atrium (LA) wall deformation. The aims of this study were to assess the feasibility of measuring regional longitudinal strain/strain rate (epsilon/SR) profiles in the LA wall, to define the normal values and to validate these measurements. METHODS AND RESULTS: MVI data were recorded in 40 healthy young individuals using a GE Vivid7 for the lateral, anterior and inferior LA walls. The peak epsilon/SR values and total epsilon values during the contractile, reservoir and conduit LA phases were measured. For the LA lateral wall, the total epsilon values were correlated with the LA volumetric indicators (LA active emptying fraction: LA AEF; LA expansion index: LA EI; and LA passive emptying fraction: LA PEF). The correlations were significant for all three periods: contractile (total epsilon vs. LA AEF, r=-0.78, P<0.001), reservoir (total epsilon vs. LA EI, r=0.43, P<0.01) and conduit (total epsilon vs. LA PEF, r=-0.46, P<0.005). CONCLUSION: SR/epsilon imaging for the quantification of longitudinal myocardial LA deformation was shown to be feasible and the normal values were reported and validated. These data may improve the understanding of the LA pathophysiology.


Asunto(s)
Ecocardiografía Doppler , Atrios Cardíacos/diagnóstico por imagen , Contracción Miocárdica/fisiología , Adolescente , Adulto , Análisis de Varianza , Estudios de Factibilidad , Femenino , Humanos , Masculino , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados
11.
West Afr. j. med ; 25(3): 174-178, 2006. ilus
Artículo en Inglés | AIM (África) | ID: biblio-1273426

RESUMEN

Objective: To determine if intraoperative magnetic resonance imaging improves surgical resection and postoperative outcome of intracranial meningioma. Study design: Prospective; on-randomized; cohort study Method: Intraoperative Magnetic Resonance Imaging (iMRI) was used to evaluate patients with meningioma undergoing surgery. Images were obtained after induction of anaesthesia and at various stages of tumour resection. Extent of surgical resection was graded using Simpson grading system for meningioma. The images were reviewed together with histopathology and early outcome. Primary outcome measure was determined by finding unexpected tumur in interdissection images. Secondary outcome measures were determined by postoperative complications including infections and mortalities. Results: There were 39 procedures in 38 patients from January 1998 to December 2002. Surgical-planning images helped to optimize craniotomy placement. Interdissection images revealed unexpected residual tumour in only 1 patient. Complete resection (Simpson grades 1-3) was achieved in 33 procedures. The average follow up period was 16.4 months. Tumour recurrence has been observed in three patients. Two of these patients had anaplastic meningioma. There was no mortality in the 30-day postoperative period. Conclusion: Intraoperative MRI was beneficial in siting the craniotomy in addition to providing anatomical relationships between the tumour and adjacent structures in lesions located at the skull base though the full benefit of these is yet to be determined. The low morbidity and zero mortality recorded in the study may be related to all these factors


Asunto(s)
Imagen por Resonancia Magnética , Mastectomía Segmentaria , Meningioma
12.
Clin Genet ; 68(5): 436-41, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16207211

RESUMEN

Frequency of truly cryptic subtelomere abnormalities - a study of 534 patients and literature review. Unbalanced subtelomere chromosome rearrangements are a significant cause of mental retardation with approximately 5% of over 3000 affected individuals tested worldwide having a chromosome rearrangement of this type. Many of these abnormalities are detectable using routine karyotyping at the 550 band level and therefore are not considered to be cryptic. The frequency of truly cryptic subtelomere abnormality should be less than 5% but has not been established. In this study, we defined 'cryptic abnormality' as one not detectable at the 550 band level on routine karyotyping. Using this as one of the selection criteria, we have studied 534 individuals with mental retardation/ developmental delay (MR/DD) and referred for subtelomere study by clinical geneticists. We have identified seven cases with cryptic subtelomere abnormalities. The clinical features of the seven abnormal cases are summarized. Literature review identified five publications on the identification of subtelomere abnormalities which used similar recruitment criteria: (a) normal karyotype at the 550 band level and (b) subjects were selected for subtelomere studies. Combining the data from these studies with those of the current study, 1154 patients were tested and 30 subtelomere abnormalities were identified. We estimate the frequency of truly cryptic subtelomere abnormality to be approximately 2.6% (30/1154) in children with MR/DD who are referred for subtelomere study.


Asunto(s)
Anomalías Múltiples/genética , Aberraciones Cromosómicas , Discapacidades del Desarrollo/genética , Frecuencia de los Genes , Discapacidad Intelectual/genética , Adolescente , Anciano , Centrómero , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Cariotipificación , Masculino , Telómero
13.
Heart ; 91(10): 1343-8, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15761045

RESUMEN

OBJECTIVES: To examine whether the line dividing the septum into two layers is found consistently by conventional echocardiography and to evaluate functional differences in the right and left side of the septum in terms of wall thickening, strain rate, and strain imaging. DESIGN: In a systematic study in 30 normal subjects, M mode and Doppler myocardial imaging data from the interventricular septum (IVS) were recorded. Velocity curves, regional strain rate, and strain profiles were obtained. Systolic deformation (wall thickening, radial and longitudinal strain rate, and strain) of both sides were assessed. Furthermore, three patients with one sided abnormalities were studied. RESULTS: A bright echo consistently segmented the IVS into a left and right part. In this normal population radial deformation was different for the left and right side of the septum (mean (SD) wall thickening on the left, 49 (46)%, and on the right, 17 (38)%; strain rate on the left, 3.8 (0.6) 1/s, and on the right, 2.1 (1.9) 1/s; strain on the left, 41 (17)%, and on the right, 22 (14)%), whereas longitudinal deformation was found to be similar (strain rate on the left, -2.2 (0.7) 1/s, and on the right, -2.0 (0.6) 1/s; strain on the left, -28 (12)%, and on the right, -25 (12)%). The presented clinical examples show that abnormalities can be strictly limited to one layer. CONCLUSIONS: Differential radial deformation and knowledge of fibre architecture showing an abrupt change in the middle of the septum, together with the clinical cases, suggest the septum to be a morphologically and functionally bilayered structure potentially supplied by different coronary arteries.


Asunto(s)
Tabiques Cardíacos/fisiología , Adolescente , Adulto , Cardiomegalia/diagnóstico por imagen , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Ecocardiografía , Ecocardiografía Doppler en Color , Femenino , Tabiques Cardíacos/anatomía & histología , Tabiques Cardíacos/diagnóstico por imagen , Humanos , Masculino , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Función Ventricular
14.
Horm Res ; 62(4): 208-14, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15452386

RESUMEN

BACKGROUND/AIMS: Two half-brothers with similar malformed genitals, who both inherited a maternally derived t(X;5)(q13;p15) translocation, have a phenotype consistent with partial androgen sensitivity syndrome. The aim was to identify the gene disrupted by the X chromosome breakpoint. METHODS: The breakpoint was localized using fluorescence in situ hybridization to metaphase spreads of the translocation. RESULTS: The breakpoint on the X chromosome of the X;5 translocation was localized to a 30-kb region. This region does not contain any identified genes or transcripts. However, the breakpoint is approximately 134 kb from the 5' end of the androgen receptor (AR) gene. CONCLUSIONS: Genetic defects of the AR gene are collectively called androgen insensitivity syndrome and include a range of phenotypes from normal males, often with associated sterility, to XY females. The phenotype seen in the males with the t(X;5) is consistent with this syndrome. The analysis of the chromosomal abnormality suggests that this translocation may remove one or more upstream regulatory elements of the AR gene that are essential for its normal expression and its role in typical external masculinization.


Asunto(s)
Síndrome de Resistencia Androgénica/genética , Cromosomas Humanos X , Receptores Androgénicos/genética , Translocación Genética , Línea Celular , Cromosomas Humanos X/genética , Secuencia Conservada , Femenino , Silenciador del Gen , Humanos , Immunoblotting , Hibridación Fluorescente in Situ , Recién Nacido , Masculino , Linaje , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia
15.
Ultrasound Med Biol ; 30(5): 591-8, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15183223

RESUMEN

Strain rate imaging (SRI) is a new ultrasound (US) approach to the quantification of regional myocardial deformation. It previously has been validated in vitro and in vivo against other imaging techniques. However, in all such studies, only peak strain values were compared, and the temporal evolution of the strain curve was not studied. Yet, it is the temporal evolution of the strain curves that contains the more important clinical information (e.g., asynchrony, viability, etc). Thus, the aim of this study was to compare the evolution of strain during the complete cardiac cycle as measured by US SRI, US grey-scale M-mode and magnetic resonance imaging (MRI). In 10 healthy volunteers and 20 patients with chronic ischaemic heart disease, radial deformation of the inferolateral segment of the left ventricle was measured by US SRI, US M-mode and MRI. The correspondence of the temporal characteristics of these strain curves were compared by defining an intraclass correlation coefficient (ICC). In healthy volunteers, an overall good agreement (mean ICC: 0.75 and 0.63 for systole and diastole) was found between the different methods. However, in patients with abnormal segmental deformation and low peak strain values, the agreement was less (mean ICC: 0.42 and 0.32), but remained within acceptable limits for clinical decision making. Myocardial deformation measurements using SRI correlated well with MRI and US M-mode measurements throughout the complete cardiac cycle.


Asunto(s)
Ecocardiografía Doppler en Color/métodos , Imagen por Resonancia Magnética/métodos , Contracción Miocárdica/fisiología , Isquemia Miocárdica/fisiopatología , Miocardio , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/patología , Estenosis Coronaria/fisiopatología , Femenino , Corazón/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/patología , Factores de Tiempo
16.
Cytogenet Genome Res ; 100(1-4): 77-84, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14526166

RESUMEN

Rare folate-sensitive fragile sites are the archetypal trinucleotide repeats. Although the CAG repeat in the androgen receptor, associated with spinobulbar muscular atrophy, was the first to be published in 1991, it was the publication in the same year of the molecular basis of fragile X that focused much attention on trinucleotide repeat expansion as a mutational mechanism. A number of rare fragile sites have had their repeat elements characterised since that time. The so-called "folate-sensitive" fragile sites are likely to be all CCG repeat expansions similar to the fragile X. The folate insensitive fragile sites have more complex longer repeat elements. Only two rare fragile sites (FRAXA and FRAXE) are of unequivocal clinical significance in that they are associated with intellectual disability.


Asunto(s)
Sitios Frágiles del Cromosoma/genética , Mapeo Cromosómico , Humanos , Cariotipificación , Modelos Genéticos , Expansión de Repetición de Trinucleótido/genética
17.
Cytogenet Genome Res ; 100(1-4): 89-91, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14526168

RESUMEN

Fragile sites have been recognised since 1965. Extensive molecular characterisation of them has occurred in the last decade. Yet there are a number of interesting phenomena relating to fragile sites and similar lesions on chromosomes that have not been subject to recent published research. The aim of this short review is to stimulate interest in some of these aspects of fragile sites in the hope that a more complete picture of their nature and properties will emerge.


Asunto(s)
Sitios Frágiles del Cromosoma/genética , Antimetabolitos Antineoplásicos/farmacología , Azacitidina/farmacología , Bromodesoxiuridina/farmacología , Aberraciones Cromosómicas/inducido químicamente , Análisis Citogenético , Humanos
18.
Eur Heart J ; 24(17): 1584-94, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12927194

RESUMEN

AIMS: To develop optimal methods for the objective non-invasive diagnosis of coronary artery disease, using myocardial Doppler velocities during dobutamine stress echocardiography. METHODS AND RESULTS: We acquired tissue Doppler digital data during dobutamine stress in 289 subjects, and measured myocardial responses by off-line analysis of 11 left ventricular segments. Diagnostic criteria developed by comparing 92 normal subjects with 48 patients with coronary disease were refined in a prospective series of 149 patients referred with chest pain. Optimal diagnostic accuracy was achieved by logistic regression models, using systolic velocities at maximal stress in 7 myocardial segments, adjusting for independent correlations directly with heart rate and inversely with age and female gender (all p<0.001). Best cut-points from receiver-operator curves diagnosed left anterior descending, circumflex and right coronary disease with sensitivities and specificities of 80% and 80%, 91% and 80%, and 93% and 82%, respectively. All models performed better than velocity cut-offs alone (p<0.001). CONCLUSION: Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography is best performed using diagnostic models based on segmental velocities at peak stress and adjusting for heart rate, and gender or age.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Cardiotónicos , Enfermedad de la Arteria Coronaria/fisiopatología , Dopamina , Ecocardiografía Doppler , Ecocardiografía de Estrés/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Regresión
19.
Eur J Echocardiogr ; 4(2): 81-91, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12749869

RESUMEN

BACKGROUND: Ultrasonic strain rate and strain can characterize regional one-dimensional myocardial deformation at rest. In theory, these deformation indices could be used to quantify normal or abnormal regional function during a dobutamine stress echo test. AIMS: The aims of our pilot study were threefold: (1) to determine the percentage of segments in which interpretable strain rate/strain data could be obtained during routine dobutamine stress echo, (2) to establish whether either the increase in heart rate or artefacts induced by respiration during dobutamine stress echo would influence analysis by degrading the data and (3) to determine the optimal frame rate vs image sector angle settings for data acquisition. Furthermore, although the detection of ischaemia was not to be addressed specifically in this study, we would describe the findings on the potential clinical role of regional deformation vs velocity imaging in detecting ischaemia-induced changes. METHODS: A standard dobutamine stress echo protocol was performed in 20 consecutive patients with a history of chest pain (16 with angiographic coronary artery disease and four with normal coronary angiograms). DMI velocities were acquired at baseline, low dose, peak dose, and recovery. To evaluate radial function (basal segment of the left ventricle posterior wall segment), parasternal LAX, SAX views were used. For long axis function data were acquired (4-CH, 2-CH views) from the septum; lateral, inferior and anterior left ventricle walls. Data was acquired using both 15 degrees (>150 frames per second (fps) and 45 degrees (115fps) sector angles. During post-processing each wall was divided into three segments: basal, mid and apical. Strain rate/strain values were averaged over three consecutive heart cycles. RESULTS: Data was obtained from 1936 segments, of which only 54 had to be excluded from subsequent analysis (2.8%) because of suboptimal quality. An increase in heart rates (up to 150/min) was not associated with a significant reduction in the number of interpretable segments. There was a significant correlation between maximal systolic strain rate/strain values obtained at narrow and at wide sector angles (e.g. a correlation for the septal segments: r=0.73,P <0.001 for strain rate, and r=0.71; P<0.001 for strain). The correlation for the timing of events obtained from narrow and wide sector angles was weaker. This would indicate that there was the insufficient temporal resolution for the latter acquisition method. Normal and abnormal regional strain rate/strain responses to an incremental dobutamine infusion were defined. In normal segments, maximal systolic strain rate values increased continuously from baseline, reaching the highest values at the peak dose of dobutamine. The segmental strain response was different. For strain, there was an initial slight increase at low dose of dobutamine (5, 10 microg/kg/min), but no further increase with increasing dose. A pattern representing an ischaemic response was identified and described. CONCLUSIONS: The feasibility study would suggest that with appropriate data collection and post-processing methodologies, strain rate/strain imaging can be applied to the quantification of dobutamine stress echo. However, appropriate post-processing algorithms must be introduced to reduce data analysis time in order to make this a practical clinical technique.


Asunto(s)
Ecocardiografía de Estrés , Aumento de la Imagen , Adulto , Anciano , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Velocidad del Flujo Sanguíneo/fisiología , Cardiotónicos/administración & dosificación , Angiografía Coronaria , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/fisiología , Estenosis Coronaria/diagnóstico , Estenosis Coronaria/fisiopatología , Dobutamina/administración & dosificación , Relación Dosis-Respuesta a Droga , Estudios de Factibilidad , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Contracción Miocárdica/efectos de los fármacos , Contracción Miocárdica/fisiología , Proyectos Piloto , Estadística como Asunto , Estimulación Química , Función Ventricular Izquierda/efectos de los fármacos , Función Ventricular Izquierda/fisiología
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