Numerical simulations of phase contrast velocity mapping of complex flows in an anatomically realistic bypass graft geometry

Combined in vitro experiments and numerical simulations were performed to study flow artifacts in phase contrast (PC) velocity mapping of steady flow through an anatomically realistic aortocoronary bypass graft model. The geometry was obtained through imaging and computational reconstruction of a left anterior descending (LAD) coronary artery of a porcine heart. Simulated images of through-plane velocity were obtained at selected slices of the geometry. These were then compared and contrasted with velocity images of corresponding sites that were obtained from in vitro experiments. The shift and distortion of the measured velocity profile was well predicted by the simulation, while trajectories obtained from particle tracking were shown to be useful in understanding the origins of the flow artifacts that were observed.     

Recurrent nasopharyngeal carcinoma masquerading as acoustic neuroma

This is the first report of recurrent nasopharyngeal carcinoma (NPC) presenting as a cerebellopontine angle mass. The clinical presentation, investigation and management of this case, as well as the confusion and dilemma caused, are discussed. We hope to increase awareness on the multifaceted ways in which recurrent NPC could present and to share the lessons learnt from our management of this unusual and unfortunate case.     

Triplanar control dynamic response orthoses based on new concepts in lower limb orthotics

With new insight and solution development backed with evidence, new medical tools for individuals in need of orthotic treatment are available. More research is needed to validate further and improve techniques and outcomes. More clinicians need to be trained and develop the skills to master the techniques. Outcome-driven results will keep raising the bar of quality and proficiency to enhance the lives of individuals who depend on orthotists.     

An atypical kindred with X-linked adrenal hypoplasia congenita, normal puberty, and normal Dax-1 promoter and coding sequence

We report a Chinese kindred with an atypical sex-linked form of isolated adrenal hypoplasia without hypogonadotropic hypogonadism. Evidence of sex linkage was supported by DNA analysis using three polymorphic markers from the X-chromosome: a restriction fragment length polymorphism 200 kb centromeric of the DAX-1 gene, a tetranucleotide repeat marker in the DAX-1 promoter (DAX-P), and a microsatellite in the Duchenne muscular dystrophy locus (3'-19). This pedigree therefore presents the novel phenotype of sex-linked hypoadrenalism without hypogonadotropic hypogonadism, with evidence of possible linkage to the DAX-1 gene. However, all three affected individuals were examined for mutations in the DAX-1 gene, and found to have no sequence anomalies in the coding region, splice sites or 5' non-coding region. This presentation may be due to a defect in the DAX-1 gene outside its known coding region, possibly modulated by functional polymorphisms at other loci, and/or environmental effects, or to a defect in a novel gene on the X chromosome which selectively influences adrenal development.     

Chitinase and Fizz family members are a generalized feature of nematode infection with selective upregulation of Ym1 and Fizz1 by antigen-presenting cells

Ym1 and Fizz1 are secreted proteins that have been identified in a variety of Th2-mediated inflammatory settings. We originally found Ym1 and Fizz1 as highly expressed macrophage genes in a Brugia malayi infection model. Here, we show that their expression is a generalized feature of nematode infection and that they are induced at the site of infection with both the tissue nematode Litomosoides sigmodontis and the gastrointestinal nematode Nippostrongylus brasiliensis. At the sites of infection with N. brasiliensis, we also observed induction of other chitinase and Fizz family members (ChaFFs): acidic mammalian chitinase (AMCase) and Fizz2. The high expression of both Ym1 and AMCase in the lungs of infected mice suggests that abundant chitinase production is an important feature of Th2 immune responses in the lung. In addition to expression of ChaFFs in the tissues, Ym1 and Fizz1 expression was observed in the lymph nodes. Expression both in vitro and in vivo was restricted to antigen-presenting cells, with the highest expression in B cells and macrophages. ChaFFs may therefore be important effector or wound-repair molecules at the site of nematode infection, with potential regulatory roles for Ym1 and Fizz1 in the draining lymph nodes.     

Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility

Malignant hyperthermia susceptibility (MHS) is a subclinical pharmacogenetic disorder caused by an impairment of skeletal muscle calcium homeostasis in response to triggering agents. While in vitro contracture testing (IVCT) is the gold standard for defining MHS, molecular analysis is increasingly used to diagnosis MHS. Mutations associated with MHS have been reported in two genes: RYR1 and CACNA1S. Mutations in RYR1 are also responsible for central core disease (CCD), a myopathy that can be associated with a positive IVCT response. We report here the results of correlation studies performed with molecular, pharmacological, histological, and functional data obtained in 175 families (referred to as confirmed (129) or potential (46) MHS families). Extensive molecular analysis allowed us to identify a variant in 60% of the confirmed MHS families, and resulted in the characterization of 11 new variants in the RYR1 gene. Most mutations clustered to MH1 and MH2 domains of RYR1. Functional analysis allowed us to assign a causative role for seven MHS mutations that we propose to add to the panel of MHS mutations used for genetic testing. The use of genetic data to determine MHS status led to a 99.5% sensitivity for IVCT. IVCT-positive/mutation-negative diagnoses were analyzed not only in terms of specificity for IVCT, but also to assess the presence of a second MHS trait in families, and the genetic heterogeneity of the disease. Histological analyses revealed the presence of cores in more than 20% of muscle biopsies originating from 242 genotyped and tested MHS patients who did not present with clinical symptoms. This indicates that these patients must be considered as MHS patients with cores, and are clearly differentiated from CCD patients who have been tested positive for MHS.