3.0-T MR Imaging of Intracoronary Local Delivery of Motexafin Gadolinium Into Coronary Artery Walls.

3.0-T MR Imaging of Intracoronary Local Delivery of Motexafin Gadolinium into Coronary Artery Walls.

Radiology. 2013 Mar 19;
Meng Y, Wang J, Sun J, Zhang F, Willis P, Li J, Wang H, Zhang T, Soriano S, Qiu B, Yang X

Purpose:To develop a technique with clinical 3.0-T magnetic resonance (MR) imaging to delineate local contrast agent distribution in coronary artery walls for potential molecular MR imaging-guided local gene or drug therapy of atherosclerotic coronary artery disease.Materials and methods:This animal protocol was approved by the institutional animal care and use committee and was in compliance with the Guide for the Care and Use of Laboratory Animals. For in vitro confirmation, human arterial smooth muscle cells (SMCs) were used to determine capability of SMCs in uptake of motexafin gadolinium (MGd) and its optimal dose. For ex vivo evaluation, a 2-mL mixture of MGd and trypan blue was locally infused into coronary artery walls of six cadaveric pig hearts with MR monitoring and an MR imaging guidewire, surface coils, or both. For in vivo validation, the balloon catheter was placed into coronary arteries of seven living pigs, and the MGd and trypan blue mixture was infused into arterial walls with MR guidance. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of coronary artery walls were recorded by using different coils between pre- and postcontrast infusion, with subsequent histologic confirmation. Paired Student t tests were used to compare average SNRs and CNRs of arterial walls before and after contrast agent infusion with different coils.Results:SMCs could take up MGd with the optimal concentration at 150 µmol/L. Average SNR with the MR imaging guidewire and surface coil combination was significantly higher than that with the MR imaging guidewire only or with surface coils only (P < .05), and average SNR and CNR of postinfusion MR imaging was significantly higher than that of preinfusion MR imaging (P < .05). Histologic analysis was used to confirm successful intracoronary infiltration of MGd and trypan blue within coronary artery walls.Conclusion:MR imaging can be used to delineate locally infused contrast agent distribution in coronary artery walls. This establishes groundwork for development of molecular MR imaging-guided intracoronary therapy.© RSNA, 2013Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13121451/-/DC1. HubMed – drug


Analysis of Over 10,000 Cases Finds No Association between Previously-Reported Candidate Polymorphisms and Ovarian Cancer Outcome.

Cancer Epidemiol Biomarkers Prev. 2013 Mar 19;
White KL, Vierkant RA, Fogarty Z, Charbonneau B, Block MS, Pharoah PD, Chenevix-Trench G, Rossing MA, Cramer DW, Pearce L, Schildkraut JM, Menon U, Kruger Kjær S, Levine DA, Gronwald J, Anton-Culver H, Whittemore AS, Karlan BY, Lambrechts D, Wentzensen N, Kupryjanczyk J, Chang-Claude J, Bandera EV, Hogdall EV, Heitz F, Kaye S, Fasching PA, Campbell IG, Goodman MT, Pejovic T, Bean YT, Lurie G, Eccles D, Hein A, Beckmann MW, Ekici AB, Paul J, Brown R, Flanagan JM, Harter P, du Bois A, Schwaab I, Hogdall CK, Lundvall L, Olson SH, Orlow I, Paddock LE, Rudolph A, Eilber U, Dansonka-Mieszkowska A, Rzepecka IK, Ziolkowska-Seta I, Brinton LA, Yang HP, Garcia-Closas M, Despierre E, Lambrechts S, Vergote I, Walsh C, Lester J, Sieh W, McGuire V, Rothstein JH, Ziogas A, Lubinski J, Cybulski C, Menkiszak J, Jensen A, Gayther SA, Ramus SJ, Gentry-Maharaj A, Berchuck A, Wu AH, Pike MC, Van Den Berg D, Terry KL, Vitonis AF, Doherty JA, Johnatty SE, Defazio A, Song H, Tyrer J, Sellers TA, Phelan CM, Kalli KR, Cunningham JM, Fridley BL, Goode EL

BACKGROUND: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNPs) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. METHODS: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000 observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. RESULTS: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. CONCLUSIONS: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. HubMed – drug


Azathioprine hypersensitivity presenting as septic shock with encephalopathy.

BMJ Case Rep. 2013; 2013:
James A, Blagojevic J, Benham SW, Cornall R, Frater J

We present a case of azathioprine hypersensitivity presenting as septic shock with associated encephalopathy. The patient was presented with rapid onset of fever, hypotension, confusion and a rapidly declining conscious level. He was admitted to the intensive care unit where he received numerous invasive investigations and treatments with broad-spectrum antibiotics, antivirals and antifungals. All microbial cultures were negative. The patient-consistent with azathioprine hypersensitivity-made a spontaneous recovery after 7 days. The case shows that a time line of drug initiation is a key part of the medical history and consideration of azathioprine hypersensitivity could avoid unnecessary interventions and excessive antimicrobial use. HubMed – drug


Linezolid-induced serotonin syndrome.

BMJ Case Rep. 2013; 2013:
Gupta V, Karnik ND, Deshpande R, Patil MA

A young drug abuser was admitted to our intensive care unit for organophosphorus poisoning. He required mechanical ventilation and was started empirically on linezolid for suspected nosocomial infection. The patient developed high-grade fever with altered sensorium and clonus. Serotonin syndrome was suspected and the patient was started on cyproheptadine. He recovered within 3 days of withdrawing linezolide and administering cyproheptadine. HubMed – drug



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