EXT2-positive multiple hereditary osteochondromas with some features suggestive of metachondromatosis

Metachondromatosis (MC) and hereditary multiple osteochondromas (HMO) are thought to be distinct disorders, each with characteristic x-ray and clinical features. Radiographic differences are the current mainstay of differential diagnosis. Both disorders are autosomal dominant, but the majority of patients with HMO have mutations in EXT-1 or EXT 2 genes. The genetic defect in MC is unknown, although recent studies indicate a possible identifiable mutation. The cancer risk in HMO is thought to be greater than in MC, although the small number of cases make such conjecture imprecise. The purpose of this report is to review existing literature and examine whether radiographic findings in HMO and MC can be reliable as a stand-alone means of differential diagnosis. Three members of a multi-generational family with an autosomal dominant exostosis syndrome were studied by clinical examination and complete skeletal survey. The roentgenographic characteristics of all osteochondromas were analyzed. The father underwent gene sequencing for EXT-1 and EXT-2, which revealed a novel EXT-2 mutation. Typical radiographic and clinical findings of both HMO and MC were seen throughout the family as well as in individuals. These family study findings contradict many of the long-standing clinical and x-ray diagnostic criteria for differentiating MC from HMO. The phenotypic crossover between the two conditions in this family, and results of genetic analysis, suggest that in the absence of a definitive genetic diagnosis, radiographic and clinical diagnosis of past and future cases HMO and MC may not be as reliable as previously assumed.     

Hyperpolarized 129Xe gas lung MRI–SNR and T2* comparisons at 1.5 T and 3 T

In this study, the signal‐to‐noise ratio of hyperpolarized ¹²⁹Xe human lung magnetic resonance imaging was compared at 1.5 T and 3 T. Experiments were performed at both B₀ fields with quadrature double Helmholtz transmit–receive chest coils of the same geometry with the same subject loads. Differences in sensitivity between the two field strengths were assessed from the signal‐to‐noise ratio of multi‐slice 2D ¹²⁹Xe ventilation lung images obtained at the two field strengths with a spatial resolution of 15 mm × 4 mm × 4 mm. There was a systematically higher signal‐to‐noise ratio observed at 3 T than at 1.5 T by a factor of 1.25. Mean image signal‐to‐noise ratio was in the range 27–44 at 1.5 T and 36–51 at 3 T. T of ¹²⁹Xe gas in the partially inflated lungs was measured to be 25 ms and 18 ms at 1.5 T and 3 T, respectively. T of ¹²⁹Xe gas in fully inflated lungs was measured to be 52 ms and 24 ms at 1.5 T and 3 T, respectively. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Flow cytometric detection of platelet-reactive antibodies and application in platelet crossmatching

Background: Alloimmunization against HLA or platelet antigens can cause refractoriness to platelet transfusions in multiply transfused patients. Crossmatching of platelet concentrates is effective in overcoming this problem. Study Design and Methods: A flow cytometric assay was used for simultaneous detection of lymphocyte-reactive and platelet-reactive antibodies in a single sample using fluorescein isothiocyanate-labeled anti-IgG. This assay was compared with the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay in selected sera containing HLA and platelet antibodies. In a further study, this assay was compared with lymphocytotoxicity test results from thrombocytopenic patients, for whom platelet concentrates were ordered. The results of both assays were then correlated with the 1-hour corrected count increment, with a corrected count increment greater then 7500 considered as an adequate transfusion response. Results: The results of the MAIPA and flow cytometric assay in detecting platelet-reactive antibodies correlated well (p<0.0001, r = 0.84). The sensitivity and specificity of the flow cytometric assay in detecting platelet-reactive antibodies were 94.7 and 96.3 percent, when the MAIPA assay was taken as a reference. In unselected sera from patients, the sensitivity and specificity of the flow cytometric assays were, respectively, 72.7 and 91.7 percent in detecting lymphocyte- reactive antibodies and 70.6 and 77.7 percent in detecting platelet- reactive antibodies, when the lymphocytotoxicity test was used as a reference. With regard to an adequate transfusion response, the sensitivities and efficiencies were 20.0 and 82.1 percent, 33.3 and 84.3 percent, and 70.0 and 88.6 percent for the lymphocytotoxicity test and the lymphocyte-reactive and platelet-reactive flow cytometric assays, respectively. Conclusion: Flow cytometric crossmatching appears to be an effective method of detecting platelet-reactive antibodies that may affect the success of platelet transfusions. This procedure is well-suited for routine conditions and can be performed within 2 hours.     

Evaluation of potential losartan-phenytoin drug interactions in healthy volunteers

BACKGROUND: Phenytoin, a cytochrome P450 (CYP) 2C9 substrate, has a narrow therapeutic index and nonlinear pharmacokinetics. Therefore there is the potential for significant concentration-related adverse effects when phenytoin is coadministered with other CYP2C9 substrates. Losartan, an antihypertensive agent, is also a substrate for CYP2C9. OBJECTIVE: Our objective was to assess the effects of losartan on the pharmacokinetics of phenytoin and the effects of phenytoin on the pharmacokinetics of losartan in a healthy population of volunteers. METHODS: A prospective, randomized, 3-period crossover study was conducted in 16 healthy volunteers with phenytoin alone, phenytoin in combination with losartan, and losartan alone. Each treatment was given for 10 days with a 3-week washout period between treatments. On day 10, plasma concentrations of phenytoin and plasma and urine concentrations of losartan and its active carboxylic-acid metabolite E3174 were measured to determine steady-state pharmacokinetic parameters. RESULTS: Coadministration of losartan had no effect on the pharmacokinetics of phenytoin. Coadministration of phenytoin increased the mean area under the concentration-time curve from time zero to 24 hours [AUC(0-24)] of losartan by 17% (355 +/- 220 ng x h/mL versus 427 +/- 177 ng x h/mL; P =.1), but this difference was not statistically significant. In the 14 CYP2C9*1/*1 subjects, the mean AUC(0-24) of losartan was increased by 29% (284 +/- 84 ng x h/mL versus 402 +/- 128 ng x h/mL; P =.008). Coadministration of phenytoin significantly reduced the AUC(0-24) of E3174 by 63% (1254 +/- 256 ng x h/mL versus 466 +/- 174 ng x h/mL; P =.0001) and the formation clearance of losartan to E3174 (1.91 +/- 0.8 mL/h per kilogram versus 0.62 +/- 0.4 mL/h per kilogram; P =.0001). CONCLUSIONS: Losartan, a CYP2C9 substrate, had no effect on the pharmacokinetics of phenytoin. However, phenytoin inhibited the CYP2C9-mediated conversion of losartan to E3174.     

Pediatric intestinal transplantation: normal radiographic appearance and complications

We present a pictorial essay on pediatric intestinal transplantation that describes the indications for pediatric intestinal transplantation, surgical technique, and the role of imaging in the pre-transplant work-up and detection of post-transplant complications. We illustrate the normal post-transplant imaging appearance and common complications, including rejection, infection, post-transplant lymphoproliferative disease (PTLD), mechanical dysfunction and vascular complications. We conclude with an imaging algorithm for suspected post-transplant complications based on clinical scenarios.     

The antiviral role of zinc and metallothioneins in hepatitis C infection

Metallothioneins (MTs) are small, cysteine‐rich proteins characterized by a high affinity for monovalent and divalent cations, such as copper and zinc. Of the four known MT isoforms, only, members of the MT 1 and 2 subfamilies are widely expressed, acting as metal chaperones whose primary role is to mediate intracellular zinc homoeostasis. Metallothioneins are potently induced by heavy metals and other sources of oxidative stress where they facilitate metal binding and detoxification as well as free radical scavenging. Metallothionein expression is well documented in the context of viral infection; however, it remains uncertain whether MTs possess specific antiviral roles or whether induction is merely a consequence of cellular stress. To better understand the role of MTs following hepatitis C virus (HCV) infection, we examined MT expression and localization in vitro and in vivo and used a siRNA knockdown approach to ascertain their antiviral efficacy. We confirmed HCV‐driven MT induction in vitro and demonstrated MT accumulation in the nucleus of HCV‐infected hepatocytes by immunofluorescence. Using a pan‐MT siRNA to knock down all members of the MT1 and MT2 subfamilies, we demonstrate that they are mildly antiviral against the JFH1 strain of HCV in vitro (~1.4 fold increase in viral RNA, P < .05). Furthermore, the antiviral effect of zinc treatment against HCV in vitro was mediated through MT induction (P < .05). Our data suggest a potential benefit of using zinc as a low‐cost adjunct to current HCV antiviral therapies and suggest that zinc may facilitate the antiviral role of MTs against other viruses.