The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by mutation of the telomeric survival motor neuron 1 (SMN1) gene with retention of the centromeric SMN2 gene. We sought to establish whether the potent and specific hydroxamic acid class of histone deacetylase (HDAC) inhibitors activates SMN2 gene expression in vivo and modulates the SMA disease phenotype when delivered after disease onset. Single intraperitoneal doses of 10 mg/kg trichostatin A (TSA) in nontransgenic and SMA model mice resulted in increased levels of acetylated H3 and H4 histones and modest increases in SMN gene expression. Repeated daily doses of TSA caused increases in both SMN2-derived transcript and SMN protein levels in neural tissues and muscle, which were associated with an improvement in small nuclear ribonucleoprotein (snRNP) assembly. When TSA was delivered daily beginning on P5, after the onset of weight loss and motor deficit, there was improved survival, attenuated weight loss, and enhanced motor behavior. Pathological analysis showed increased myofiber size and number and increased anterior horn cell size. These results indicate that the hydroxamic acid class of HDAC inhibitors activates SMN2 gene expression in vivo and has an ameliorating effect on the SMA disease phenotype when administered after disease onset.

Of all procedures in interventional radiology, percutaneous transhepatic biliary drainage (PTBD) is amongst the most technically challenging. Successful placement requires a high level of assorted skills. While this procedure can be life-saving, it can also lead to significant iatrogenic harm, often manifesting as bleeding. Readers of this article will come to understand the pathophysiology and anatomy underlying post-PTBD bleeding, its incidence, its varied clinical manifestations and its initial management. Additionally, a structured approach to its treatment emphasizing endovascular and percutaneous methods is given.

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CT-guided, percutaneous cryoablation has an excellent safety and efficacy profile for stage T1A and T1B RCC; however, longer follow-up is needed to compare it with other nephron-sparing surgical treatments. It is a great option for nonsurgical patients, those in whom renal function cannot be further sacrificed, and those at risk for metachronous lesions.

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