Nelarabine (ara-G; Arranon; compound 506U78) is an antineoplastic purine analog used for the treatment of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). The drug was granted accelerated approval in October 2005 by the US Food and Drug Administration (FDA) given the efficacy (induction of complete responses) noted in 2 single-arm trials (one in pediatric setting and one in adult patient population). The main spectra of toxicities that have been reported in these clinical trials and subsequent studies are hematological and neurological. Nelarabine induced rhabdomyolysis and increased creatinine phosphokinase (CK; CPK) levels apparently have been reported and this side effect has been added as an adverse reaction in the product monograph from the drug company during postmarketing surveillance. However, the true extent and incidence of the myotoxicity from the drug are unclear. In this paper we report a grade IV CK elevation and rhabdomyolysis in a patient with T-ALL treated with nelarabine. Given the reported finding, we examined the literature further for myotoxicity, increased CK, and/or rhabdomyolysis associated with the use of the nelarabine and report our findings.
Unconscious Race and Social Class Bias Among Acute Care Surgical Clinicians and Clinical Treatment Decisions
Compressive sensing (CS) describes how sparse signals can be accurately reconstructed from many fewer samples than required by the Nyquist criterion. Since MRI scan duration is proportional to the number of acquired samples, CS has been gaining significant attention in MRI. However, the computationally intensive nature of CS reconstructions has precluded their use in routine clinical practice. In this work, we investigate how different throughput-oriented architectures can benefit one CS algorithm and what levels of acceleration are feasible on different modern platforms. We demonstrate that a CUDA-based code running on an NVIDIA Tesla C2050 GPU can reconstruct a 256 × 160 × 80 volume from an 8-channel acquisition in 19 seconds, which is in itself a significant improvement over the state of the art. We then show that Intel's Knights Ferry can perform the same 3D MRI reconstruction in only 12 seconds, bringing CS methods even closer to clinical viability.
Mutation in Glycerol-3-Phosphate Dehydrogenase 1–Like Gene (
GPD1-L
) Decreases Cardiac Na
+
Current and Causes Inherited Arrhythmias
Background— Brugada syndrome is a rare, autosomal-dominant, male-predominant form of idiopathic ventricular fibrillation characterized by a right bundle-branch block and ST elevation in the right precordial leads of the surface ECG. Mutations in the cardiac Na + channel SCN5A on chromosome 3p21 cause ≈20% of the cases of Brugada syndrome; most mutations decrease inward Na + current, some by preventing trafficking of the channels to the surface membrane. We previously used positional cloning to identify a new locus on chromosome 3p24 in a large family with Brugada syndrome and excluded SCN5A as a candidate gene. Methods and Results— We used direct sequencing to identify a mutation (A280V) in a conserved amino acid of the glycerol-3-phosphate dehydrogenase 1–like ( GPD1-L ) gene. The mutation was present in all affected individuals and absent in >500 control subjects. GPD1-L RNA and protein are abundant in the heart. Compared with wild-type GPD1-L, coexpression of A280V GPD1-L with SCN5A in HEK cells reduced inward Na + currents by ≈50% ( P <0.005). Wild-type GPD1-L localized near the cell surface to a greater extent than A280V GPD1-L. Coexpression of A280V GPD1-L with SCN5A reduced SCN5A cell surface expression by 31±5% ( P =0.01). Conclusions— GPD1-L is a novel gene that may affect trafficking of the cardiac Na + channel to the cell surface. A GPD1-L mutation decreases SCN5A surface membrane expression, reduces inward Na + current, and causes Brugada syndrome.