RESUMEN

Mono(2-ethylhexyl) phthalate (MEHP), the main di(2-ethylhexyl) phthalate (DEHP) metabolite, is a known reproductive toxicant. Residual levels of 20 nM MEHP have been found in follicular fluid aspirated from IVF-treated women and DEHP-treated animals. The current study examined whether these residual MEHP levels have any effect on the follicle-enclosed oocyte or developing embryo. Bovine oocytes were matured with or without 20 nM MEHP for 22 h. Microarray analysis was performed for both mature oocytes and 7-day blastocysts. A proteomic analysis was performed on mature oocytes (n = 200/group) to reveal a possible direct effect on the oocyte proteomic profile. Transcriptome analysis revealed MEHP-induced alterations in the expression of 456 and 290 genes in oocytes and blastocysts, respectively. The differentially expressed genes are known to be involved in various biological pathways, such as transcription process, cytoskeleton regulation and metabolic pathway. Among these, the expression of 9 genes was impaired in both oocytes exposed to MEHP (i.e., direct effect) and blastocysts developed from those oocytes (i.e., carryover effect). In addition, 191 proteins were found to be affected by MEHP in mature oocytes (Data are available via ProteomeXchange with identifier PXD012092). The study explores, for the first time, the risk associated with exposing oocytes to low concentration (i.e., environmentally relevant concentration) of MEHP to the maternal transcripts. Although it was the oocytes that were exposed to MEHP, alterations carried over to the blastocyst stage, following embryonic genome activation, implying that these embryos are of low quality.

Asunto(s)

Blastocisto/efectos de los fármacos , Dietilhexil Ftalato/análogos & derivados , Oocitos/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Animales , Blastocisto/metabolismo , Bovinos , Células Cultivadas , Dietilhexil Ftalato/toxicidad , Desarrollo Embrionario/efectos de los fármacos , Femenino , Oocitos/crecimiento & desarrollo , Oocitos/metabolismo , Proteómica

RESUMEN

During the last few years, several co-culture systems using either BOEC or VERO feeder cells have been developed to improve bovine embryo development and these systems give better results at high oxygen concentration (20%). In parallel, the SOF medium, used at 5% O2, has been developed to mimic the oviduct fluid. Since 2010s, the SOF medium has become popular in improving bovine embryo development and authors have started to associate this medium to co-culture systems. Nevertheless, little is known about the putative benefit of this association on early development. To address this question, we have compared embryo transcriptomes in four different culture conditions: SOF with BOEC or VERO at 20% O2, and SOF without feeders at 5% or 20% O2 Embryos have been analyzed at 16-cell and blastocyst stages. Co-culture systems did not improve the developmental rate when compared to 5% O2 Direct comparison of the two co-culture systems failed to highlight major differences in embryo transcriptome at both developmental stages. Both feeder cell types appear to regulate the same cytokines and growth factors pathways, and thus to influence embryo physiology in the same way. In blastocysts, when compared to culture in SOF at 5% O2, BOEC or VERO seems to reduce cell survival and differentiation by, at least, negatively regulating STAT3 and STAT5 pathways. Collectively, in SOF medium both blastocysts rate and embryo transcriptome suggest no influence of feeder origin on bovine early development and no beneficial impact of co-culture systems when compared to 5% O2.

Asunto(s)

Bovinos , Técnicas de Cocultivo/métodos , Técnicas de Cultivo de Embriones/métodos , Desarrollo Embrionario/genética , Regulación del Desarrollo de la Expresión Génica , Transcriptoma , Animales , Blastocisto/citología , Blastocisto/metabolismo , Bovinos/embriología , Bovinos/genética , Células Cultivadas , Medios de Cultivo/farmacología , Embrión de Mamíferos , Desarrollo Embrionario/efectos de los fármacos , Células Nutrientes/citología , Células Nutrientes/fisiología , Femenino , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Masculino , Transcriptoma/efectos de los fármacos

RESUMEN

The number of polymorphisms identified with next-generation sequencing approaches depends directly on the sequencing depth and therefore on the experimental cost. Although higher levels of depth ensure more sensitive and more specific SNP calls, economic constraints limit the increase of depth for whole-genome resequencing (WGS). For this reason, capture resequencing is used for studies focusing on only some specific regions of the genome. However, several biases in capture resequencing are known to have a negative impact on the sensitivity of SNP detection. Within this framework, the aim of this study was to compare the accuracy of WGS and capture resequencing on SNP detection and genotype calling, which differ in terms of both sequencing depth and biases. Indeed, we have evaluated the SNP calling and genotyping accuracy in a WGS dataset (13X) and in a capture resequencing dataset (87X) performed on 11 individuals. The percentage of SNPs not identified due to a sevenfold sequencing depth decrease was estimated at 7.8% using a down-sampling procedure on the capture sequencing dataset. A comparison of the 87X capture sequencing dataset with the WGS dataset revealed that capture-related biases were leading with the loss of 5.2% of SNPs detected with WGS. Nevertheless, when considering the SNPs detected by both approaches, capture sequencing appears to achieve far better SNP genotyping, with about 4.4% of the WGS genotypes that can be considered as erroneous and even 10% focusing on heterozygous genotypes. In conclusion, WGS and capture deep sequencing can be considered equivalent strategies for SNP detection, as the rate of SNPs not identified because of a low sequencing depth in the former is quite similar to SNPs missed because of method biases of the latter. On the other hand, capture deep sequencing clearly appears more adapted for studies requiring great accuracy in genotyping.

Asunto(s)

Técnicas de Genotipaje/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN/métodos , Animales , Pollos/genética , Genoma , Genotipo

RESUMEN

Juvenile rheumatoid arthritis (JRA) is mediated by Th1-immune responses. In children with JRA, synovial T cells express high levels of the Th1-chemokine receptor CC chemokine receptor 5 (CCR5), which has been implicated in susceptibility to rheumatoid arthritis. To test the hypothesis that genetic variation in CCR5 is associated with susceptibility to JRA, we analyzed patterns of variation in the 5'cis-regulatory region of CCR5 in 124 multiplex families from a JRA-affected sibpair registry. After sequencing the upstream region of CCR5, variants were tested for association with JRA by transmission disequilibrium testing. A single nucleotide polymorphism, C-1835T, was significantly undertransmitted to children with early-onset JRA (P<0.01). C-1835T was genotyped in 424 additional simplex and multiplex families. CCR5-1835T allele was undertransmitted in the cohort of all probands with JRA (P<0.02), as well as in those with early-onset (P<0.01) or pauciarticular JRA (P<0.05). Another variant, a 32-bp deletion in the open reading frame of CCR5 (CCR5-Delta32) was also tested in approximately 700 simplex and multiplex families. CCR5-Delta32 was also significantly undertransmitted to probands with early-onset JRA (P<0.05). Both variants are in regions under natural selection, and result in functional consequences. Our results suggest these CCR5 variants are protective against early-onset JRA.

Asunto(s)

Artritis Juvenil/genética , Polimorfismo Genético , Receptores CCR5/genética , Secuencia de Bases , Niño , Preescolar , Estudios de Cohortes , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple

RESUMEN

OBJECTIVE: To assess the reproductive fitness of mothers of children with juvenile idiopathic arthritis (JIA). METHODS: A mail survey assessing pregnancy outcome was carried out among mothers of children with JIA (JIA mothers) treated at a tertiary paediatric rheumatology centre. The best friends of the JIA mothers served as controls. Besides family history, sociodemographics and reproductive outcomes were measured, including the number of pregnancies, pregnancy complications and gestational age at the time of delivery. RESULTS: JIA mothers (n = 227) and controls (n = 235) had similar sociodemographics and racial backgrounds. On average, JIA mothers reported a greater number of conceptions than controls (3.5 vs 3.1; P = 0.01) but had significantly higher rates of pregnancy complications (25% vs 15%; P<0.001). Corrected for differences in the absolute number of pregnancies between groups, the chances of having a miscarriage [mean (s.d.), 0.12 (0.18) vs 0.09 (0.16); P = 0.02] or preterm delivery [0.08 (0.21) vs 0.04 (0.15); P<0.02] were significantly greater among JIA mothers than controls. CONCLUSIONS: Mothers of children with JIA have impaired reproductive fitness. This phenomenon is unlikely to be the result of difficulty with conception but rather to be due to higher rates of pregnancy loss and premature delivery.

Asunto(s)

Artritis Juvenil , Madres , Complicaciones del Embarazo , Aborto Espontáneo , Adolescente , Estudios de Casos y Controles , Niño , Femenino , Número de Embarazos , Indicadores de Salud , Humanos , Recién Nacido , Trabajo de Parto Prematuro , Paridad , Embarazo , Resultado del Embarazo , Mortinato

RESUMEN

OBJECTIVE: To evaluate the ability of microarray-based methods to identify genes with disease-specific expression patterns in peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) of juvenile arthritis patients and healthy controls. METHODS: Microarray data (Affymetrix U95Av2) from 26 PBMC and 20 SFMC samples collected from patients with active disease (classified by course according to ACR criteria) were analysed for expression patterns that correlated with disease characteristics. For comparison, PBMC gene expression profiles were obtained from 15 healthy controls. Real-time PCR was used for confirmation of gene expression differences. RESULTS: Statistical analysis of gene expression patterns in PBMC identified 378 probe sets corresponding to 342 unique genes with differing expression levels between polyarticular course patients and controls (t test, P<0.0001). The genes represented by these probe sets were enriched for functions related to regulation of immune cell functions, receptor signalling as well as protein metabolism and degradation. Included in these probe sets were a group of CXCL chemokines with functions related to angiogenesis. Further analysis showed that, whereas angiogenic CXCL (ELR+) gene expression was elevated in polyarticular PBMC, expression of angiostatic CXCL (ELR-) chemokines was lower in polyarticular SFMC compared with corresponding pauciarticular samples (t test, P<0.05). CONCLUSIONS: This pilot study demonstrates that juvenile arthritis patients exhibit complex patterns of gene expression in PBMC and SFMC. The presence of disease-correlated biologically relevant gene expression patterns suggests that the power of this approach will allow better understanding of disease mechanisms, identify distinct clinical phenotypes in disease subtypes, and suggest new therapeutic approaches.

Asunto(s)

Artritis Juvenil/genética , Quimiocinas CXC/genética , Expresión Génica/genética , Leucocitos Mononucleares/fisiología , Espondiloartropatías/genética , Líquido Sinovial/fisiología , Adolescente , Adulto , Células Cultivadas , Niño , Perfilación de la Expresión Génica/métodos , Humanos , Neovascularización Patológica/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Proyectos Piloto , Proteínas Tirosina Quinasas/genética , Estudios Retrospectivos , Transducción de Señal/genética , Transactivadores/genética

RESUMEN

We report herein the results of the cross-cultural adaptation and validation into the Argentinian language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Argentinian CHAQ was already published and therefore it was revalidated while the Argentinian CHQ was derived from the European Spanish version by changing few words which use is different in the 2 countries. A total of 124 subjects were enrolled: 61 patients with JIA (29% systemic onset, 38% polyarticular onset, 7% extended oligoarticular subtype, and 26% persistent oligoarticular subtype) and 63 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, and polyarticular having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Argentinian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Asunto(s)

Artritis Juvenil/diagnóstico , Estado de Salud , Encuestas y Cuestionarios , Adolescente , Argentina , Niño , Comparación Transcultural , Características Culturales , Evaluación de la Discapacidad , Femenino , Humanos , Lenguaje , Masculino , Psicometría , Calidad de Vida , Reproducibilidad de los Resultados

RESUMEN

To determine the effects of chronic Ag stimulation on B cell survival and phenotype, we compared survival and surface markers of hen egg lysozyme (HEL)-specific B cells in Ig transgenic (Tgn) mice, which lack HEL, and in HEL-Ig transgenic mice, which express soluble HEL. Serum HEL levels were maximized in HEL-Ig Tgn mice by feeding them zinc, which activates the metallothionein promoter that regulates HEL expression. B cell age was characterized by expression of heat-stable Ag, and B220 and B cell survival was studied by evaluating changes in B cell number when lymphopoiesis was suppressed with anti-IL-7 mAb and by identifying newly generated B cells through 5-bromo-2'-deoxyuridine incorporation. Our observations show that the mean B cell life span is considerably reduced in HEL-Ig Tgn compared with Ig Tgn mice, but also demonstrate that some HEL-Ig Tgn B cells survive to maturity. Some of these surviving B cells have undergone receptor editing (substitution of an endogenous Ig light chain for the transgenic Ig light chain), so that their ability to bind HEL is decreased or absent. Surviving HEL-Ig Tgn B cells that retain HEL specificity express decreased mIgD and little or no mIgM. mIgD expression progressively decreases with increasing HEL-Ig Tgn B cell age. These observations suggest that self Ag-specific B cells can survive in the presence of soluble self Ag by down-regulating mIg expression, which should limit B cell signaling by Ag that might otherwise cause deletion of these cells.

Asunto(s)

Linfocitos B/citología , Linfocitos B/inmunología , Animales , Anticuerpos Monoclonales/administración & dosificación , Linfocitos B/metabolismo , Linfocitos B/trasplante , Sitios de Unión de Anticuerpos/genética , Bromodesoxiuridina/metabolismo , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Supervivencia Celular/genética , Supervivencia Celular/inmunología , Femenino , Inmunoglobulina D/biosíntesis , Inmunoglobulina D/genética , Inmunoglobulina D/metabolismo , Inmunoglobulina M/biosíntesis , Inmunoglobulina M/genética , Inmunoglobulina M/metabolismo , Inmunofenotipificación , Inyecciones Intraperitoneales , Interleucina-7/inmunología , Depleción Linfocítica , Linfopenia/genética , Linfopenia/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Muramidasa/inmunología , Muramidasa/metabolismo , Receptores de Antígenos de Linfocitos B/biosíntesis , Receptores de Antígenos de Linfocitos B/genética , Receptores de Antígenos de Linfocitos B/metabolismo , Bazo/citología , Bazo/inmunología , Factores de Tiempo

RESUMEN

OBJECTIVE: To define the onset and duration of effect of the HLA alleles that are associated with disease susceptibility and protection in juvenile rheumatoid arthritis (JRA) and 2 of its subtypes. METHODS: We typed 680 patients with JRA and 254 ethnically matched unrelated controls for HLA class I and II genes. The frequency of each allele was calculated for each of the age-at-onset, onset type, and sex categories and plotted against the allele frequency in the control population. Survival analysis (with onset of disease as the terminating event) was used to calculate the age by which 50% (St0.5) and 80% (St0.2) of the children with particular alleles and combinations of alleles develop disease. This allele-specific survival analysis also allowed for the comparison of the overall survival functions for the various JRA subtype and sex categories. RESULTS: Certain alleles are strongly associated with early susceptibility to pauciarticular JRA, including HLA-A2, DR8, DR5, and DPB1*0201. Fifty percent of the children carrying at least 1 of these alleles had disease onset prior to their third birthday. Among children who carried HLA-A2 and any 2 HLA-DR alleles (DR3, DR5, DR6, or DR8), the median age at the onset of pauciarticular disease was 2.7 years. Combinations of A2 and DPB1*0201 and one DR allele narrowed the window further to a median age at onset of 2.4 years. B27 and DR4 were associated with protection early in life but with increased risk later in childhood, with St0.5 values of 7.3 and 6.6 years, respectively, for pauciarticular JRA and St0.5 values of 10.2 and 10.7 years, respectively, for polyarticular JRA. Sex strongly influenced the age at which many of the alleles have their effect. CONCLUSION: These data define at what age and for how long various HLA alleles influence susceptibility and protection (window-of-effect) in patients with JRA. In addition, these data establish more clearly the boundaries of ages-at-onset for 2 of the subtypes of the disease.

Asunto(s)

Artritis Juvenil/genética , Artritis Juvenil/inmunología , Antígenos HLA/genética , Factores de Edad , Alelos , Niño , Preescolar , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Antígeno HLA-B27/genética , Antígeno HLA-DR1/genética , Antígeno HLA-DR4/genética , Antígeno HLA-DR5/genética , Antígeno HLA-DR6/genética , Humanos , Lactante , Recién Nacido , Masculino , Factores de Tiempo

RESUMEN

OBJECTIVES: To translate into Argentine Spanish and cross-culturally adapt the Childhood Health Assessment Questionnaire (CHAQ) and validate the adapted instrument in Argentine patients with juvenile rheumatoid arthritis (JRA). METHODS: Five bilingual Argentine pediatric rheumatologists translated into Argentine Spanish and cross-culturally adapted the United States English CHAQ. Pretesting was done in a sample of 23 parents using a probe question technique. Parents of 70 patients with JRA and 21 healthy children (controls) participated in the validation phase. All were from Argentina. RESULTS: The mean disability index (DI) scores for patients with systemic, polyarticular, or pauciarticular onset JRA were 0.64, 0.32, and 0.1, respectively. Healthy controls averaged 0.2. Intercomponent correlations were between 0.4 and 0.9, suggesting internal consistency, but also some redundancy. Test-retest reliability, studied at a 1-week interval, was moderate (mean DI 0.44 [in clinic] and 0.29 [one week later], Pearson's correlation = 0.82). We compared CHAQ scores from 15 parents with those of their children > 10 years of age. Significantly higher DI scores were given by patients than their respective parents (P > 0.019), but the pairwise scores (parent-patient) were highly correlated (r = 0.986). CONCLUSIONS: Cross-cultural adaptation of the US CHAQ to Argentina required few changes. Although DI scores for all patient subgroups were higher than for controls subjects, the scores were low, particularly for those with pauciarticular disease. Prospective studies designed to examine the sensitivity to change and predictive validity will help to assess further the usefulness of the adapted CHAQ in the Argentine population.

Asunto(s)

Actividades Cotidianas , Artritis Juvenil/etnología , Artritis Juvenil/fisiopatología , Personas con Discapacidad/clasificación , Estado de Salud , Encuestas y Cuestionarios/normas , Traducción , Adolescente , Argentina , Estudios de Casos y Controles , Niño , Preescolar , Comparación Transcultural , Humanos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Estados Unidos

RESUMEN

OBJECTIVE: To determine if HLA class I and II alleles previously found to be associated with (or protective against) pauciarticular-onset juvenile rheumatoid arthritis (pauci-onset JRA) in population-association studies are transmitted from heterozygous parents to an extent different from the expected 50%. METHODS: One hundred one Caucasian North American families that had a child with pauci-onset JRA and at least 1 parent who was heterozygous for the allele of interest were available for analysis. Both biologic parents and all children (affected and unaffected) were typed for HLA class I and II alleles. The transmission disequilibrium test (TDT) was used to determine if affected offspring received the disease-associated (or protective) allele more (or less) frequently than its alternate allele. In families in which an unaffected sibling was available, the unmatched chi-square test was used to determine if a meiotic segregation distortion bias existed. RESULTS: HLA class I alleles A2, B27, and B35 showed a significantly higher than expected frequency of transmission to affected offspring, as did class II alleles DR5 and DR8. HLA-DR4 was found to be transmitted significantly less frequently than expected to affected, but not unaffected, offspring. All alleles that showed an excess transmission to affected offspring were transmitted to unaffected offspring at expected rates. When the data were stratified by age and sex, the likelihood of transmission of some of the alleles was strongly influenced by these variables. For example, excess transmission of HLA-DR5 was found exclusively in female patients who were younger at the time of disease onset. CONCLUSION: Results from these family-based studies rule out the possibility that HLA disease associations found in earlier studies were a result of population stratification and establish linkage and association between the major histocompatibility complex and pauci-onset JRA.

Asunto(s)

Artritis Juvenil/genética , Antígenos HLA/genética , Desequilibrio de Ligamiento/genética , Adolescente , Adulto , Alelos , Artritis Juvenil/patología , Niño , Preescolar , Femenino , Heterogeneidad Genética , Prueba de Histocompatibilidad , Humanos , Lactante , Recién Nacido , Masculino

RESUMEN

INTRODUCTION: Transcranial color Doppler sonography permits the accurate assessment of intracranial arteries. The latest Doppler units, using the color and power techniques, can show even very small flow volumes (1 x 1 mm). Low frequency (2-2.5 MHz) and very focused transducers are used in transcranial color Doppler. The skull is a very strong barrier for ultrasounds, which requires the use of some acoustic windows like some thin portions of the skull bone or some natural skull foramina. The use of echocontrast agents in color Doppler seems to increase the applications of transcranial studies. OBJECTIVE: (1) To report on transcranial color Doppler technique and findings. (2) To assess the role of contrast agents in the visualization of intracranial vessels. (3) To define the main indications of this technique. MATERIAL AND METHODS: The temporal, the orbital and the suboccipital are the main acoustic windows used for transcranial color Doppler studies. We use phased-array transducers (2-2.5 MHz) and, preferrably, the echocontrast agent. We examined 15 patients with severe internal carotid artery stenoses after the infusion of Levovist (Schering AG, Berlin, Germany) suspension (8 ml at 300 mg Galactose/ml, infused at 0.5 ml/s). RESULTS: Levovist infusion permitted to depict the main intracranial vessels in all cases. The middle and the anterior cerebral arteries are shown through the temporal window. The former is the main cerebral artery, it is the easiest to identify and presents the highest peak systolic velocity. The orbital window can be used to visualize the ophthalmic artery and the internal carotid artery siphon, while the vertebral and the basilar arteries are demonstrated through the suboccipital window. DISCUSSION: We report the most important findings and discuss the main indications of transcranial color Doppler studies. In addition to flow presence and direction, the main indices of arterial flow can be measured thanks to contrast agent administration, namely the peak systolic velocity, the end diastolic velocity, the resistance index and the pulsatility index. A morphological assessment of the Willis circle can also be carried out with color and power Doppler. Functional studies can be performed to assess the residual autoregulatory function of the cerebral circle in the patients with internal carotid artery stenosis or occlusion. The development of intracranial collateral circles can also be studied in these patients. Moreover, the M1 segment of the middle cerebral artery and the internal carotid artery siphon can be demonstrated directly. Transcranial color Doppler is also a useful tool to detect vasospasm after subarachnoid hemorrhage and to monitor blood flow velocity in the middle cerebral artery during carotid endarterectomy. The assessment of blood supply to arteriovenous malformations and to intracranial neoplasms is another application. CONCLUSION: With reference to internal carotid stenoses, the main applications of transcranial color Doppler are the study of intracranial vessels, of intracranial arterial stenosis, of arteriovenous malformations and of Willis circle aneurysms, as well as the monitoring of blood flow velocity during carotid endarterectomy. Echocontrast agents play an important role in the visualization of intracranial vessels.

Asunto(s)

Encéfalo/irrigación sanguínea , Medios de Contraste/administración & dosificación , Polisacáridos/administración & dosificación , Ultrasonografía Doppler Transcraneal , Arteriopatías Oclusivas/diagnóstico por imagen , Velocidad del Flujo Sanguíneo/fisiología , Estenosis Carotídea/diagnóstico por imagen , Humanos , Valores de Referencia , Sensibilidad y Especificidad , Hemorragia Subaracnoidea/diagnóstico por imagen , Ultrasonografía Doppler en Color

RESUMEN

INTRODUCTION: MRI is a very accurate technique to study the elbow joint, tendon, ligament and chondral structures. In the last years elbow disorders were described by several MR investigators, while we studied MR capabilities in depicting normal elbow anatomy. This investigation might permit the correct differentiation of normal from abnormal MR patterns. MATERIAL AND METHODS: Eleven healthy volunteers (6 men and 5 women, mean age: 27.5 years) were examined. All studies were performed on a 1.5 T imager (Magnetom SP 4000) with two types of receiver: the knee coil was used in 7 volunteers examined in the prone position, with the arm above their head, the elbow extended and the forearm supine and the shoulder coil was used in 4 volunteers examined in the prone position, with the arm above their head, the elbow flexed and the forearm prone. We acquired T1-weighted SE sequences (TR/TE = 690/15 ms, FA 90 degrees, MA 256 x 512, NEX 2,20 3-mm sections with .3-mm interslice gap, FOV 20-22 cm) on the axial, coronal and sagittal planes and T2-weighted GE sequences (TR/TE = 450/10 ms, MA 256 x 256, 3 NEX, 18 4-mm sections with .4-mm interslice gap, FOV 13-18 cm) on the coronal plane. Two MR-expert radiologists studied the images and identified the main anatomical structures of the elbow and 12 smaller reference elements (2 anatomical variants, 4 ligaments, 3 nerves and 3 arteries) describing their MR appearance and pointing out the most effective planes for their representation. Finally, the image quality of the knee coil was compared with that of the shoulder coil. RESULTS: All bones were clearly depicted on the coronal and axial planes, while the semilunar groove and its anatomical variants were best seen on the sagittal plane. The joint cartilage was best depicted on the coronal plane with T2-weighted GE sequences. Collateral ligaments were best seen with the elbow extended and the forearm supine (knee coil), on coronal T1-weighted SE images, where the radial and ulnar collateral ligaments were visible in 71.4% and 85.7% of the subjects, respectively. Annular ligaments, muscles and tendons were best demonstrated on the axial plane with the elbow extended and the forearm supine (knee coil), while the triceps tendon was best recognized on the sagittal plane with the elbow flexed and the forearm prone (shoulder coil). Vessels and nerves were also best seen on the axial plane with the elbow extended and the forearm supine; in particular, the median nerve was visible in 71.4% of the subjects. DISCUSSION AND CONCLUSION: MRI is very effective in representing elbow anatomical structures. Its accuracy depends on elbow (flexed or extended) and forearm (prone or supine) position. The coronal images with the elbow extended and the forearm supine (knee coil) are the most effective to show the ligaments and the joint surfaces between the radial head and the coronoid process of ulna with the capitellum and trochlea of distal humerus, while the axial images best depicted the muscles, vessels and nerves. The coronal and axial planes, with the elbow flexed and the forearm prone (shoulder coil) are poorly effective for anatomical detailing, even though this position is more comfortable for the patient, while the sagittal plane is best suited to depict the triceps tendon. This position may be used when the elbow cannot be fully extended or when the triceps tendon is studied.

Asunto(s)

Codo/anatomía & histología , Codo/patología , Imagen por Resonancia Magnética , Adulto , Femenino , Humanos , Masculino

RESUMEN

OBJECTIVE: To investigate the ability of various definitions of improvement to distinguish between patients with juvenile rheumatoid arthritis (JRA) treated with active drug from those given placebo in randomized trials. METHODS: A core set of 6 response (outcome) variables for use in JRA has been reported. These core variables were combined into a number of "definitions of improvement" for the purpose of classifying individual patients as either "clinically significantly improved" or "not improved." We used a large dataset from randomized controlled trials to test the discriminant ability (sensitivity to change) of the definitions. We calculated the proportion of patients classified as "improved" by each definition in each of the treatment and control groups. RESULTS: Effect sizes were weak in 4 of the treatment regimens used (D-penicillamine, hydroxychloroquine, auranofin, and very low dose methotrexate) and no definition discriminated well between drug and placebo treated groups. Definitions that required 20 to 30% improvement in 3 to 4 of the 6 core set variables showed statistically significant differences in the proportions of patients who were classified as improved in the group treated with low dose methotrexate (10 mg/m2 body surface area/wk) compared to placebo. A definition resembling the Paulus criteria used in adult RA trials (4 of 6 core set variables improved by > or = 20%) performed well, as did the definition selected previously as the best for JRA (3 of 6 core set variables improved by > or = 30%, not more than one worsening by > 30%). CONCLUSION: Definitions that require 20 to 30% improvement in 3 to 4 core outcome variables are sensitive to change and are able to clearly distinguish between treated and control groups when an effective drug is being tested. Further testing of their validity is under way.

Asunto(s)

Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Auranofina/uso terapéutico , Análisis Discriminante , Humanos , Hidroxicloroquina/uso terapéutico , Metotrexato/uso terapéutico , Penicilamina/uso terapéutico , Placebos , Resultado del Tratamiento

RESUMEN

OBJECTIVE: To describe the demographics and clinical disease in affected sibpairs (ASPs) with juvenile rheumatoid arthritis (JRA), and to compare JRA as it occurs in ASPs with that from non-ASP JRA populations described in the literature. METHODS: A rare disease research registry was established with a focus on JRA ASPs to facilitate accrual of patients for genetic, epidemiologic, and clinical studies. Physicians likely to care for patients with JRA were made aware of the registry and its goals by a variety of methods and asked to refer patients for entry. RESULTS: To date, 71 ASPs have been registered and complete information has been obtained. These affected sibs differed in age by a mean of 4.1 years (SD 3.4) and in age at disease onset by 2.8 years (SD 3.0). The actual time difference between onset in sib 1 versus sib 2 averaged 4.4 years (SD 4.2). Sixty-three percent of the sibpairs were concordant for sex, and 76% for JRA onset type. Onset type within sibpairs did not appear to be random, based upon comparisons with non-ASP populations. Greater than expected concordance was seen among those with pauciarticular-onset and polyarticular-onset JRA. Seventy-nine percent of the pairs were concordant for course type. Seven sets of twins were included (approximately 10% of the total), all were concordant for onset and course type (6 sets with pauciarticular, 1 set with polyarticular), and disease onset was separated by a mean of only 3.3 months. Within the onset and course types, the clinical disease, such as the female:male ratio, age at onset, and serologic findings, in ASPs resembled that which has been described in the literature. CONCLUSION: A higher than expected degree of concordance for onset type of JRA exists between sibpairs, indicating that genetic influences play a role. Affected sibs do not tend to develop their disease at approximately the same point in time, except for the twin sets. Clinical features of the disease within the various subtypes appear similar to those in non-ASP populations.

Asunto(s)

Artritis Juvenil/genética , Edad de Inicio , Anticuerpos Antinucleares/sangre , Artritis Juvenil/sangre , Artritis Juvenil/epidemiología , Niño , Preescolar , Enfermedades en Gemelos/epidemiología , Salud de la Familia , Femenino , Humanos , Lactante , Masculino , Relaciones entre Hermanos