Distribution and sources of variability of sister-chromatid exchange frequencies in cattle*

International audienc

Genetic structure and population dynamics of autochthonous and modern porcine breeds. Analysis of the IGF2 and MC4R genes that determine carcass characteristics

To know the genetic situation of the Pampa Rocha, Celta, Bizaro Portuguese, Duroc, Iberian Extremeno and Iberian Andalusian porcine populations. their genetic structure and population dynamics were studied on the IGF2 and MC4R genes, which determine meat characteristics and quality. The degree of genetic variability (He = 0.2511 in Pampa Rocha; 0.0278 in Celta; 0, 1453 in Bizaro Portuguese; 0.3719 in Duroc; 0.0764 in Iberian Extremeno and 0.0384 in Iberian Andalusian). genetic distance, and the presence or absence of consanguinity were studied. The Fis values were positive for the Duroc population (0.00426) indicating a very low inbreeding, the rest of the populations did not present consanguinity. Significant deviations (P <= 0.05) in the Hardy-Weinberg (HW) equilibrium were obtained for the IGF2 locus in Celta, Iberian Extreme no, and Iberian Andalusian populations with the G allele fixed, while the Bizaro Portuguese. Pampa Rocha, and Duroc populations presented polymorphism, the G allelic frequency was much higher than A allele, except in the Duroc breed (0.15). These findings could help breeders to increase the presence of the A allele for the improvement of muscle mass and reduction in the back-fat thickness in this breed. All the studied populations presented polymorphism for the MC4R locus with different frequencies for each allele. Furthermore, these results could allow developing strategies against anthropogenic activities that hinder the conservation of the biodiversity of these porcine breeds

Increased glycolipid storage produced by the inheritance of a complex intronic haplotype in the α-galactosidase A (GLA) gene

BACKGROUND: Accumulation of galactosphingolipids is a general characteristic of Fabry disease, a lysosomal storage disorder caused by the deficient activity of α-galactosidase A encoded by the GLA gene. Although many polymorphic GLA haplotypes have been described, it is still unclear whether some of these variants are causative of disease symptoms. We report the study of an inheritance of a complex intronic haplotype (CIH) (c.-10C > T, c.369 + 990C > A, c.370-81_370-77delCAGCC, c.640-16A > G, c.1000-22C > T) within the GLA gene associated with Fabry-like symptoms and galactosphingolipid accumulation. We analysed α-Gal A activity in plasma, leukocytes and skin fibroblasts in patients, and measured accumulation of galactosphingolipids by enzymatic methods and immunofluorescence techniques. Additionally, we evaluated GLA expression using quantitative PCR, EMSA, and cDNA cloning. RESULTS: CIH carriers had an altered GLA expression pattern, although most of the carriers had high residual enzyme activity in plasma, leukocytes and in skin fibroblasts. Nonetheless, CIH carriers had significant galactosphingolipid accumulation in fibroblasts in comparison with controls, and also glycolipid deposits in renal tubules and glomeruli. EMSA assays indicated that the c.-10C > T variant in the promoter affected a nuclear protein binding site. CONCLUSIONS: Thus, inheritance of the CIH caused an mRNA deregulation altering the GLA expression pattern, producing a tissue glycolipid storage

Kestenbaum procedure with posterior fixation suture for anomalous head posture in infantile nystagmus

The purpose of this study was to report the effect of combining the Kestenbaum procedure with posterior fixation suture for infantile horizontal nystagmus with anomalous head posture (AHP) in children. Nine consecutive patients who underwent combined Kestenbaum procedure plus posterior fixation suture to the recessed muscles at the same time were retrospectively studied. All patients were orthotropic before surgery and were followed for at least 6 months. Pre- and postoperative AHP and binocular corrected visual acuity (BCVA), and ocular alignment were assessed. Mean age at surgery was 4.8 ± 1.5 years. The average follow-up was 29.7 months. The average head turn preoperatively was 27.4° and postoperatively 7.2°. The average net change in AHP was 24.8° (P = 0.008). Seven of 9 patients (78%) achieved a residual head turn of 10° or less. The average Log Mar BCVA was 0.33 preoperatively and 0.31 postoperatively (P = 0.68). Only 1 patient needed additional surgery for residual horizontal AHP. No patient developed strabismus. Combined Kestenbaum procedure with posterior fixation suture was an effective and stable procedure in reducing AHP of the range of 20° to 35° in children with infantile nystagmus

Eficacia y seguridad del tratamiento con lenalidomida y dexametasona en pacientes con mieloma múltiple no candidatos a trasplante en recaída

PO-019 Introducción: En la actualidad existe una amplia diversidad de tratamientos en pacientes con Mieloma Múltiple (MM) refractarios a tratamiento en primera línea y no candidatos a trasplante de progenitores hematopoyéticos. El tratamiento de estos pacientes con lenalidomida y dexametasona ha sido una de las opciones terapeúticas más utilizadas en los últimos años. El objetivo de este estudio es evaluar la eficacia y tolerabilidad de este tratamiento en un centro hospitalario de tercer nivel. Material Y Métodos: Estudio descriptivo, observacional y retrospectivo en el que se incluyeron todos los pacientes no candidatos a TPH que iniciaron un esquema con lenalidomida entre Enero 2012 a Marzo 2019 y además recibieron al menos una línea previa de quimioterapia. Fuentes: historia clínica electrónica, registro de dispensación de pacientes ambulatorios y externos (FarmaTools) del Servicio de Farmacia. Resultados: En total 22 pacientes (50% mujeres) fueron incluidos en el estudio. La mediana de numero de líneas que recibieron previamente fue de 1(rango entre 1-2). 17 pacientes (77%) recibieron RD como 2º línea y para 5 pacientes (33%) fue la 3ª línea. Como tratamiento en 1ª línea, solo 1 paciente recibió tratamiento con QT convencional (VAD), ..

Experiencia en un centro de la suspension de inhibidores de tirosin cinasa en pacientes con lmc en respuesta molecular completa prolongada

PO-178 Introducción: Los inhibidores de tirosin cinasas (ITK) han mejorado ostensiblemente el pronóstico y evolución de los pacientes con Leucemia Mieloide Crónica (LMC). En la actualidad la remisión libre de tratamiento (RLT) está siendo considerada como un nuevo objetivo para los pacientes que presentan respuestas profundas y prolongadas, aunque la mayoría de la información corresponde a ensayos clínicos. Con la discontinuación se mejora la calidad de vida de los pacientes y es una medida de contención del gasto sanitario. Presentamos la experiencia de discontinuación de tratamiento de un centro. Pacientes y métodos: Desde 2002 hasta la actualidad hemos tratado 63 pacientes con LMC e ITK, de los que siguen en tratamiento 55 (6 muertes, 4 de ellas no por LMC y 2 pérdida de seguimiento). De ellos han discontinuado el tratamiento con ITK 15 pacientes (27%), de los cuales 3 han sido en el contexto de ensayo clínico y 12 en práctica de vida real. El motivo de discontinuación fueron efectos adversos en 3 pacientes (edemas, estreñimiento y claudicación intermitente), 3 en ensayo clínico y 9 por consenso médico/paciente. El motivo de cambio de ITK en el caso 1 fue por intolerancia, caso 2 por falta de respuesta (<RMM) a Imatinib, con presencia de la mutación G250E y en el caso 3 por falta de respuesta (<RMM). Los casos 7, 8 y 9 dentro de ensayo clínico. Se realizó monitorización de la PCR cuantitativa BCR/ABL mensual durante los primeros 6 meses y después bimensual hasta el año y posteriormente cada 3 meses. Las características de los pacientes se reflejan en Tabla 1. ..

High Frequency of Endothelial Colony Forming Cells Marks a Non-Active Myeloproliferative Neoplasm with High Risk of Splanchnic Vein Thrombosis

Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs) in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54–17.16), and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8×109/L or lower, and platelet count of 400×109/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45–13.49) Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment

Management of nystagmus in children: A review of the literature and current practice in UK specialist services

Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management