Síndrome TAR con tetrafocomelia

El síndrome TAR es un estigma genético recesivo de baja incidencia dentro de la patología ortopédica infantil general. El objetivo de este trabajo es la presentación de aquellos pacientes en donde la impregnación del síndrome es completa. Estos niños tienen en común la trombocitopenia intensa durante los primeros años de la vida, la amelia bilateral de sus miembros superiores, la fusión femorotibial y la agenesia de tibia de distinto grado. A estos síntomas se suman algunas otras con forma de presentación aislada. La importancia de su diagnóstico correcto reside en la valoración sanguínea y en la cirugía precoz de sus miembros inferiores para mejorar la «'alidad de vida. En los 7 pacientes controlados y tratados en el Servicio de Ortopedia Infantil del Hospital de Pediatría Dr. P. Garrahan se muestran las alternativas de diagnóstico diferencial y el esquema de tratamiento ortopédico quirúrgico: realineación de sus miembros inferiores, rehabilitación de sus miembros y la adaptabilidad para la marcha.The TAR syndrome is a recessive genetic anomaly of low incidence in the pediatric orthopaedic pathology. This paper reported a group of patients with complet syndrome. All of these patients had blood cell abnormalities, phocomelia of the upper extremities, femorotibial union and absence of tibia. It is very important the correct diagnosis as recurrent episodes of thrombocytopenia and early surgery of lower limbs. We report seven patients of the Garrahan Hospital of Bs.As. with the differential diagnosis, the results of surgical treatment: axial alignment and rehabilitation of the legs and walking adaptation

Análisis comparativo entre un tutor circular y uno monolateral en elongaciones óseas

El presente trabajo compara la funcionalidad de dos tutores externos utilizados para elongación: el del Dr. Ilizarov y el tutor HG, desarrollado en nuestra institución. De 131 pacientes tratados con elongación ósea en 147 huesos largos se seleccionaron al azar 25 huesos por cada aparato anteriormente mencionado. Para objetivar los resultados se registraron estadísticamente variables independientes y dependientes en sus características subjetivas y objetivas, tales como: edad, sexo, tipo de hueso elongado, tolerancia psíquica, sensación de confort, facilidad de higiene y control, las infecciones, las rigideces articulares por retracción músculo tendinosa, y la deformación ósea residual. El objetivo fue comparar y establecer si el cambio en la elección del sistema fue ventajoso para nuestros pacientes. En el intento comparativo se enfrentaron dos variables, que a nuestro criterio eran las más importantes para establecer diferencias: la calidad del callo del hueso sometido a elongación y la presencia de complicaciones tanto transitorias como definitivas.In this work we compare the results obtained with two different external fixation devices in patients undergoing bone lengthening. The devices studied were the Ilizarov type and the HG, an apparatons developed in our institution. Out of 131 patientes treated by bone lengthening in 147 long bones, 25 bones lengthened with each device were selected at random. Different subjective and objective variables were assessed: age, sex, type of bone, psichological tolerance, patients, confort, nursing, infections, joint stiffness due to musculotendinous retractions, and residual bone deformity. The aim of the study was to analyze if the monolateral frame entailed advantages for our patients. Two main factors were more deeply analysed, namely the quality of the bone callus subjected to lengthening and the presence of both transitory and definitive complications

Methylglyoxal Produced by Amyloid- Peptide-Induced Nitrotyrosination of Triosephosphate Isomerase Triggers Neuronal Death in Alzheimer’s Disease

Amyloid-β peptide (Aβ) aggregates induce nitro-oxidative stress, contributing to the characteristic neurodegeneration found in Alzheimer's disease (AD). One of the most strongly nitrotyrosinated proteins in AD is the triosephosphate isomerase (TPI) enzyme which regulates glycolytic flow, and its efficiency decreased when it is nitrotyrosinated. The main aims of this study were to analyze the impact of TPI nitrotyrosination on cell viability and to identify the mechanism behind this effect. In human neuroblastoma cells (SH-SY5Y), we evaluated the effects of Aβ42 oligomers on TPI nitrotyrosination. We found an increased production of methylglyoxal (MG), a toxic byproduct of the inefficient nitro-TPI function. The proapoptotic effects of Aβ42 oligomers, such as decreasing the protective Bcl2 and increasing the proapoptotic caspase-3 and Bax, were prevented with a MG chelator. Moreover, we used a double mutant TPI (Y165F and Y209F) to mimic nitrosative modifications due to Aβ action. Neuroblastoma cells transfected with the double mutant TPI consistently triggered MG production and a decrease in cell viability due to apoptotic mechanisms. Our data show for the first time that MG is playing a key role in the neuronal death induced by Aβ oligomers. This occurs because of TPI nitrotyrosination, which affects both tyrosines associated with the catalytic center

HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis

Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14. Of relevance, HIPK2-defective cells do not phosphorylate H2B and do not successfully complete cytokinesis leading to accumulation of binucleated cells, chromosomal instability, and increased tumorigenicity. However, how HIPK2 and H2B are recruited to the midbody during cytokinesis is still unknown. Here, we show that regardless of their direct (H2B) and indirect (HIPK2) binding of chromosomal DNA, both H2B and HIPK2 localize at the midbody independently of nucleic acids. Instead, by using mitotic kinase-specific inhibitors in a spatio-temporal regulated manner, we found that Aurora-B kinase activity is required to recruit both HIPK2 and H2B to the midbody. Molecular characterization showed that Aurora-B directly binds and phosphorylates H2B at Ser32 while indirectly recruits HIPK2 through the central spindle components MgcRacGAP and PRC1. Thus, among different cytokinetic functions, Aurora-B separately recruits HIPK2 and H2B to the midbody and these activities contribute to faithful cytokinesis

Single-level anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cage and allograft bone

BACKGROUND: In an effort to avoid the morbidity associated with autogenous bone graft harvesting, cervical cages in combination with allograft bone are used to achieve fusion. The goal of the current study was to assess the reliability and efficacy of anterior cervical discectomy and interbody fusion (ACDF) using a PEEK anatomical cervical cage in the treatment of patients affected by single-level cervical degenerative disease. METHODS AND MATERIALS: Twenty-five patients affected by single-level cervical degenerative pathology between C4 and C7 were enrolled in this study. The clinical findings were assessed using the Neck Disability Index and the Visual Analog Scale. Surgical outcomes were rated according to Odom's criteria at last follow-up. Fusion was graded as poor, average, good or excellent by assessing the radiographs. Cervical spine alignment was evaluated by sagittal segmental alignment and sagittal alignment of the whole cervical spine preoperatively, 6 months postoperatively and at the last follow-up. RESULTS: Twenty-five patients underwent ACDF using a PEEK anatomical cervical cage. All patients had a minimum 2 years of follow-up. The operative levels were C4-C5 in 5 patients, C5-C6 in 12 patients and C6-C7 in 8 patients. Preoperatively, average NDI was 34, 13 at 6 months, and 10 at latest follow-up. The mean preoperative VAS was 7; the mean postoperative VAS at latest follow-up was 3. Good or excellent fusion was achieved in all patients within 10 months (mean 5 months). Preoperatively, average sagittal segmental alignment (SSA) was 0.2\ub0 and average sagittal alignment of the cervical spine (SACS) 15.8\ub0. Six months after surgery, average SSA was 1.8\ub0 and average SACS 20.9\ub0, and at last follow-up, average SSA was 1.6\ub0 and average SACS 18.5\ub0. CONCLUSION: Anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cages can be considered a safe and effective technique to cure cervical disc herniation with intractable pain or neural deficit in cases where conservative treatment failed

Congenital hip dysplasia treated by total hip arthroplasty using cementless tapered stem in patients younger than 50 years old: results after 12-years follow-up

Background Congenital hip dysplasia may lead to severe acetabular and femoral abnormalities that can make total hip arthroplasty a challenging procedure. We assessed a series of patients affected by developmental hip dysplasia treated with total hip arthroplasty using cementless tapered stem and here we report the outcomes at long-term follow-up. Materials and methods Twenty-eight patients (24 women and 4 men) aged between 44 and 50 years (mean 47 years) were observed. Clinical evaluation was rated with the Harris Hip Score. Radiographic evaluation consisted in standard anteroposterior and axial view radiographs of the hip. According to Crowe’s classification, 16 hips presented dysplasia grade 1, 14 grade 2, and 4 grade 3. All patients were treated with total hip arthroplasty using a cementless tapered stem (Wagner Cone Prosthesis). Six patients were operated bilaterally, with a totally of 34 hips operated. After surgery, the patients were clinically and radiographically checked at 3, 6, and 12 months and yearly thereafter until an average follow-up of 12 years (range 10–14 years). Results Average Harris Hip Score was 56 ± 9 (range 45–69) preoperatively, 90 ± 9 (range 81–100) 12 months after surgery, and 91 ± 8 (range 83–100) at last follow-up. Radiographic evaluation demonstrated excellent osteointegration of the implants. Signs of bone resorption were present in 6 hips, nevertheless no evidence of loosening was observed and none of the implants has been revised. Conclusions Even in dysplasic femur, the tapered stem allowed adequate stability and orientation of the implant. We consider tapered stem a suitable option for total hip arthroplasty in developmental hip dysplasia, also in case of young patients, thanks to the favourable long-term results