RESUMEN
Molecular diagnosis for Duchenne and Becker muscular dystrophies (DMD/BMD) involves a two-tiered approach for detection of deletions/duplications using MLPA or array CGH, followed by sequencing of coding and flanking intronic regions to detect sequence variants, which is time-consuming and expensive. We have developed a comprehensive next-generation sequencing (NGS)-based single-step assay to sequence the entire 2.2 Mb of the DMD gene to detect all copy number and sequence variants in both index males and carrier females. Assay validation was 100% concordant with other methodologies. A total of 772 samples have been tested, of which 62% (N = 480) were index cases with a clinical suspicion of DMD. Carrier testing females account for 38% (N = 292). Molecular diagnosis was confirmed in 86% (N = 413) of the index cases. Intragenic deletions and duplications (single-exon or multi-exon) were detected in 60% (N = 247) and 14% (N = 58) of the index cases, respectively. Full-sequence analysis of the entire gene allows for detection of deep intronic pathogenic variants and accurate breakpoint detection of CNVs involving similar exons, which could have an impact on the outcome of clinical trials. This comprehensive assay is highly sensitive for diagnostic testing for DMD and is also suitable for confirmatory testing for newborn screening for DMD.
Asunto(s)
Distrofia Muscular de Duchenne , Tamizaje Neonatal , Distrofina/genética , Exones/genética , Femenino , Eliminación de Gen , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Recién Nacido , Masculino , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genéticaRESUMEN
We report four patients with chronic kidney disease undergoing haemodialysis therapy, which had exhausted conventional venous access (internal jugular, subclavian) and non-conventional access (axillary, innominate) in the upper hemithorax for haemodialysis. This was primarily due to thrombosis of these veins caused by previous catheterisation. These patients did not qualify for peritoneal dialysis. Using the technique recommended by Archundia et al., 4 indwelling catheters were implanted directly in the superior vena cava in each of the patients with subsequent subcutaneous tunneling. The catheters operated correctly and are currently permeable after being used for an average of 19 months.
Asunto(s)
Catéteres de Permanencia , Diálisis Renal , Vena Cava Superior , Cateterismo/métodos , Humanos , Masculino , Persona de Mediana Edad , TóraxRESUMEN
We report three patients with chronic renal failure in hemodialysis therapy, which had exhausted conventional venous access in the upper hemitórax (internal jugular, subclavian, axillary) for hemodialysis, primarily due to thrombosis of these veins by previous catheterization. We chose the technique of Rao et al. and cols for puncture of innominate vein, resulting in the implantation of catheters and their subsequent subcutaneous tunneling. Permanent catheters3 work properly and are permeable to the date after a period averaging 8 months.
Asunto(s)
Venas Braquiocefálicas , Catéteres de Permanencia , Diálisis Renal/métodos , Anciano , Cateterismo/métodos , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To establish if the implantation of catheters for hemodialysis in axillary veins is an acceptable alternative in patients with Acute or Chronic Renal Failure (ARF o CRF) with limitations for other type of central catheter. PLACE: Manizales City Hospital's Intensive Care Units and ambulatory procedure rooms of the Renal Unity RTS Ltda Caldas Subsidiary, Santa Sofia Hospital and Infantile Hospital. PATIENTS: All the patients with ARF or CRF, who required hemodialysis therapy, but that their pathology of base or the depletion of their classical access routes, required the implantation of catheters bilumenes by non conventional routes, during a period of 10 years that was extended from may 1997 to may 2007. METHODS: Those patients with ARF or CRF that required tracheostomy as support for ventilation due to their base illness; and those with ARF or CRF in whom the ambulatory or intra-hospital implantation of a central catheter for hemodialysis was not possible were carefully identified. The implantation of a double lumen central catheter for hemodialysis in axillary vein by palpation or anatomical guide was offered as an alternative to both the patients and their families. The procedure was practiced to those that accepted and gave their written consent; radiologically confirming its location; establishing their functionability at the time, as well as the complications associated to the procedure and it permanency. RESULTS: 27 procedures were practiced in 26 patients. Average age: 54.6 years; 9 women and 17 men. 7 of them had ARF and 19 CRF. In two patients the axillary vein puncture was not possible. Of the 25 axillary catheters that were implanted, 1 was permanent and 24 transitory. The technique was used by anatomical references in 16 patients and by palpation in 8. In the patients 15 left axillary veins were canalized unlike the remaining 10 that were right axillary veins. 18 patients presented impossibility of obtaining an alternative central venous access (different to femoral) and 7 patients required tracheostomy. The radiological location was satisfactorily confirmed in 24 procedures (96%). The amount of time the catheters were used was an average of 68.6 days; 6 patients died with the catheter in use. The main cause for the catheter's removal was the transference to peritoneal dialysis. The axillary artery was accidentally punctured in 3 patients, one of whom presented a soft tissue hematoma without a major hemodynamics repercussion; this had a spontaneous resolution in a few weeks. The venous canalization was not possible in 3 patients. CONCLUSIONS: The implantation of bilumenes catheters for hemodialysis in patients with ARF or CRF is a relatively safe alternative to consider when other classical routes have totally spent or the patients present tracheostomy.
Asunto(s)
Catéteres de Permanencia , Diálisis Renal/instrumentación , Axila , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To establish if the nicotinic acid in patients with chronic renal disease reduce significantly and with security the levels of lipids and serum phosphate in refractory patients to the classical management. DESIGN: Observational study Place: Renal Unity RTS Ltda Caldas Santa Sofìa Hospital. PATIENTS: All the patients with chronic renal disease in dialysis therapy to whom the classical treatment for their hyperlipidaemia and hyperphosphatemia didn't manage a satisfactory reduce of their serum levels. METHODS: It was identified that those patients who in the 3 previous months to the intervention hadn't presented changes in the lipids profile even though they received low fats diet and a lipid lowering therapies (statin o fibric acid derivates). It was determined in them whether they presented levels of serum phosphorus greater than 5.5 mg/dl even though having received nutritional recommendations and treatment with oral phosphate binding agents (Aluminum hydroxide, Calcium salts or Sevelamer). In them it was proceeded to administrate nicotinic acid via oral at night until a doses of 1,000 milligrams was reached (preceded of 100 mgs of acetylsalicylic acid 1 hour before) during a period of 8 months, observing its therapeutical effectivity and security profile to improve the lipids profile and reduce the serum phosphorus. RESULTS: 9 patients complied with the requirements, average time in dialysis 34 months, 3 in hemodialysis and 6 in peritoneal dialysis. All patients started with 500 mgs and 3 months later correctly tolerated the dose of 1,000 mgs. Between the evaluated variables, the most important changes were: the phosphorus reduced reaching a significant value at eight months: initial 6.46+/-0.53, four months 4.37+/-0.63 (p>0.05) and eight months 3.94+/-0.76 (p<0.01); the product Ca x P obtained important reductions at four and eight months; the total Cholesterol and Triglyceride was significant reduced at all periods, not being so for the LDL, although the HDL elevated to significant values at eight months. There were no significant modifications in the LDL cholesterol, intact PTH, hemoglobin, platelet count, hepatic function tests (AST, ALT and Bilirubin), coagulation tests (TTP and TP), uric acid, glycemic control, albumin, creatinine, BUN, % transferring saturation, ferritin, folic acid and Vitamin B12. No patient presented collateral or clinical effects of importance, being the adherence to the medicament 100%. CONCLUSIONS: The nicotinic acid is efficient, very well tolerated and economical in comparison with others drugs, which makes it ideal for the treatment of patients with hyperlipidaemia and refractory hyperphosphatemia to the classical treatments.
Asunto(s)
Hiperlipidemias/complicaciones , Hiperlipidemias/tratamiento farmacológico , Hiperfosfatemia/complicaciones , Hiperfosfatemia/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Enfermedades Renales/complicaciones , Niacina/uso terapéutico , Enfermedad Crónica , Femenino , Humanos , Enfermedades Renales/terapia , Masculino , Persona de Mediana Edad , Diálisis RenalRESUMEN
p21-activated kinases (Paks) play an important role in oncogenic signaling pathways and have been considered as potential therapeutic targets in various cancers. Most studies of Pak function employ gene knock-out or knock-down methods, but these approaches result in loss of both enzymatic and scaffolding properties of these proteins, and thus may not reflect the effects of small molecule inhibitors. Here we use a transgenic mouse model in which a specific peptide inhibitor of Group I Paks is conditionally expressed in response to Cre recombinase. Using this model, we show that inhibition of endogenous Paks impedes the transition of adenoma to carcinoma in an Apc-driven mouse model of colorectal cancer. These effects are mediated by inhibition of Wnt signaling through reduced ß-catenin activity as well as suppression of an epithelial-mesenchymal transition program mediated by miR-200 and Snai1. These results highlight the potential therapeutic role of Pak1 inhibitors in colorectal cancer.
Asunto(s)
Poliposis Adenomatosa del Colon/metabolismo , Neoplasias Colorrectales/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Poliposis Adenomatosa del Colon/genética , Animales , Apoptosis/genética , Apoptosis/fisiología , Proliferación Celular/genética , Proliferación Celular/fisiología , Neoplasias Colorrectales/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Células Tumorales Cultivadas , Vía de Señalización Wnt/genética , Vía de Señalización Wnt/fisiología , Quinasas p21 Activadas/genética , Quinasas p21 Activadas/metabolismoRESUMEN
Se presentan 4 pacientes con enfermedad renal crónica en terapia hemodialítica en quienes se habían agotado los accesos venosos clásicos (yugular interno, subclavio)y no clásicos (axilar e innominado) en el hemitórax superior para hemodiálisis, debido principalmente a trombosis de los mismos por cateterismos anteriores, y que no eran candidatos a diálisis peritoneal. En ellos, con la técnica recomendada por Archundia et al., se implantaron4 catéteres permanentes directamente en la vena cava superior, con posterior tunelización subcutánea. Los catéteres funcionaron adecuadamente y están permeables actualmente después de un período de utilización promedio de 19 meses (AU)
We report four patients with chronic kidney disease undergoing haemodialysis therapy, which had exhausted conventional venous access (internal jugular, subclavian) and non-conventional access (axillary, innominate) in the upper hemithorax for haemodialysis. This was primarily due tothrombosis of these veins caused by previous catheterisation. These patients did not qualify for peritoneal dialysis. Using the technique recommended by Archundia et al., 4 indwelling catheters were implanted directly in the superior vena cava in each of the patients with subsequent subcutaneous tunneling. The catheters operated correctly and are currently permeable after being used for an average of 19 months (AU)
Asunto(s)
Humanos , Vena Cava Superior/cirugía , Diálisis Renal/métodos , Insuficiencia Renal Crónica/terapia , Derivación Arteriovenosa Quirúrgica/métodos , Radiografía TorácicaRESUMEN
We report three patients with chronic renal failure in hemodialysis therapy, which had exhausted conventional venous access in the upper hemitórax(internal jugular, subclavian, axillary) for hemodialysis, primarily due to thrombosis of these veins by previous catheterization. We chose the technique of Raoandcols for puncture of in nominate vein, resulting in the implantation of catheter s and their subsequent subcutaneous tunneling. Permanent catheters3 work properly and are permeable to the date after a period averaging 8 months (AU)
Se estudian tres pacientes con enfermedad renal crónica en terapia hemodialítica, en los cuales se habían agotado los accesos venosos clásicos en el hemitórax superior (yugular interno, subclavio, axilar) para hemodiálisis, debido principalmente a trombosis de los mismos por cateterismos anteriores. En ellos se optó, mediante la técnica de Raoetal., por puncionar la vena innominada, lográndose la implantación posterior de catéteres y su tunelización subcutánea. Los catéteres permanentes3funcionaron adecuadamente y están permeables a la fecha después de un periodo promedio de ocho meses (AU)