A Case of Dilated Cardiomyopathy Associated with 3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG CoA) Lyase Deficiency

3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) lyase deficiency is an inborn error of metabolism characterized by impairment of ketogenesis and leucine catabolism resulting in an organic acidopathy. In 1994, a case of dilated cardiomyopathy and fatal arrhythmia was reported in a 7-month-old infant. We report a case of dilated cardiomyopathy in association with HMG CoA lyase deficiency in a 23-year-old man with the acute presentation of heart failure. To our knowledge, this is the first case reported in an adult

Coarsening Dynamics of a One-Dimensional Driven Cahn-Hilliard System

We study the one-dimensional Cahn-Hilliard equation with an additional driving term representing, say, the effect of gravity. We find that the driving field $E$ has an asymmetric effect on the solution for a single stationary domain wall (or `kink'), the direction of the field determining whether the analytic solutions found by Leung [J.Stat.Phys.{\bf 61}, 345 (1990)] are unique. The dynamics of a kink-antikink pair (`bubble') is then studied. The behaviour of a bubble is dependent on the relative sizes of a characteristic length scale $E^{-1}$, where $E$ is the driving field, and the separation, $L$, of the interfaces. For $EL \gg 1$ the velocities of the interfaces are negligible, while in the opposite limit a travelling-wave solution is found with a velocity $v \propto E/L$. For this latter case ($EL \ll 1$) a set of reduced equations, describing the evolution of the domain lengths, is obtained for a system with a large number of interfaces, and implies a characteristic length scale growing as $(Et)^{1/2}$. Numerical results for the domain-size distribution and structure factor confirm this behavior, and show that the system exhibits dynamical scaling from very early times.Comment: 20 pages, revtex, 10 figures, submitted to Phys. Rev.

Overcoming myelosuppression due to synthetic lethal toxicity for FLT3-targeted acute myeloid leukemia therapy.

Activating mutations in FLT3 confer poor prognosis for individuals with acute myeloid leukemia (AML). Clinically active investigational FLT3 inhibitors can achieve complete remissions but their utility has been hampered by acquired resistance and myelosuppression attributed to a 'synthetic lethal toxicity' arising from simultaneous inhibition of FLT3 and KIT. We report a novel chemical strategy for selective FLT3 inhibition while avoiding KIT inhibition with the staurosporine analog, Star 27. Star 27 maintains potency against FLT3 in proliferation assays of FLT3-transformed cells compared with KIT-transformed cells, shows no toxicity towards normal human hematopoiesis at concentrations that inhibit primary FLT3-mutant AML blast growth, and is active against mutations that confer resistance to clinical inhibitors. As a more complete understanding of kinase networks emerges, it may be possible to define anti-targets such as KIT in the case of AML to allow improved kinase inhibitor design of clinical agents with enhanced efficacy and reduced toxicity

Hiccups as a Presenting Symptom of Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic esophageal disease increasingly recognized in adults for its gastrointestinal manifestations. This paper discusses a young woman with EoE who presented with persistent hiccups and intermittent dyspepsia. The patient was initially treated with trials of both H2 blocker and proton pump inhibitor. However, her hiccups resolved only after treatment with topical fluticasone. A repeat upper endoscopy while on steroid treatment demonstrated both histologic remission of EoE and resolution of esophageal trachealization. Our patient's clinical course supports an association between hiccups and EoE, suggesting that EoE be considered in the differential diagnosis of patients with refractory hiccups

Tri-critical behavior in rupture induced by disorder

We discover a qualitatively new behavior for systems where the load transfer has limiting stress amplification as in real fiber composites. We find that the disorder is a relevant field leading to tri--criticality, separating a first-order regime where rupture occurs without significant precursors from a second-order regime where the macroscopic elastic coefficient exhibit power law behavior. Our results are based on analytical analysis of fiber bundle models and numerical simulations of a two-dimensional tensorial spring-block system in which stick-slip motion and fracture compete.Comment: Revtex, 10 pages, 4 figures available upon reques