Time filter

Source Type

Baltimore Highlands, MD, United States

Zhang X.M.,Biomedical Valley Discoveries Inc. | Zhang H.H.,Biomedical Valley Discoveries Inc. | McLeroth P.,Covance | Berkowitz R.D.,Phoenix Clinical Research | And 13 more authors.
Nuclear Medicine and Biology | Year: 2016

Introduction: Fialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [124I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [124I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections. Accurate diagnosis of prosthetic joint infections (PJIs) has proven challenging because of the lack of a well-validated reference. In the current study, we assessed biodistribution and dosimetry of [124I]FIAU, and investigated whether [124I]FIAU PET/CT can diagnose PJIs with acceptable accuracy. Methods: To assess biodistribution and dosimetry, six subjects with suspected hip or knee PJI and six healthy subjects underwent serial PET/CT after being dosed with 74 MBq (2 mCi) [124I]FIAU intravenously (IV). Estimated radiation doses were calculated with the OLINDA/EXM software. To determine accuracy of [124I]FIAU, 22 subjects with suspected hip or knee PJI were scanned at 2-6 and 24-30 h post IV injection of 185 MBq (5 mCi) [124I]FIAU. Images were interpreted by a single reader blinded to clinical information. Representative cases were reviewed by 3 additional readers. The utility of [124I]FIAU to detect PJIs was assessed based on the correlation of the patient's infection status with imaging results as determined by an independent adjudication board (IAB). Results: The kidney, liver, spleen, and urinary bladder received the highest radiation doses of [124I]FIAU. The effective dose was 0.16 to 0.20 mSv/MBq and doses to most organs ranged from 0.11 to 0.76 mGy/MBq. PET image quality obtained from PJI patients was confounded by metal artifacts from the prostheses and pronounced FIAU uptake in muscle. Consequently, a correlation with infection status and imaging results could not be established. Conclusions: [124I]FIAU was well-tolerated in healthy volunteers and subjects with suspected PJI, and had acceptable dosimetry. However, the utility of [124I]FIAU for the clinical detection of PJIs is limited by poor image quality and low specificity. © 2016 The Authors. Source

Ryoo S.,Kangwon National University | Berkowitz D.E.,The Johns Hopkins Medical Institutes | Lim H.K.,Yonsei University
Korean Journal of Anesthesiology | Year: 2011

Atherosclerotic vascular disease is the leading cause of morbidity and mortality in developed countries. While it is a complex condition resulting from numerous genetic and environmental factors, it is well recognized that oxidized low-density lipoprotein produces pro-atherogenic effects in endothelial cells (ECs) by inducing the expression of adhesion molecules, stimulating EC apoptosis, inducing superoxide anion formation and impairing protective endothelial nitric oxide (NO) formation. Emerging evidence suggests that the enzyme arginase reciprocally regulates NO synthase and NO production by competing for the common substrate L-arginine. As oxidized LDL (OxLDL) results in arginase activation/upregulation, it appears to be an important contributor to endothelial dysfunction by a mechanism that involves substrate limitation for endothelial NO synthase (eNOS) and NO synthesis. Additionally, arginase enhances production of reactive oxygen species by eNOS. Arginase inhibition in hypercholesterolemic (ApoE-/-) mice or arginase II deletion (ArgII-/-) mice restores endothelial vasorelaxant function, reduces vascular stiffness and markedly reduces atherosclerotic plaque burden. Furthermore, arginase activation contributes to vascular changes including polyamine-dependent vascular smooth muscle cell proliferation and collagen synthesis. Collectively, arginase may play a key role in the prevention and treatment of atherosclerotic vascular disease. © the Korean Society of Anesthesiologists, 2011. Source

Cicchiello L.A.,Yale University | Hamper U.M.,The Johns Hopkins Medical Institutes | Scoutt L.M.,Yale University
Obstetrics and Gynecology Clinics of North America | Year: 2011

Ultrasound should be considered the first-line imaging modality of choice in women presenting with acute or chronic pelvic pain of suspected gynecologic or obstetric origin because many, if not most, gynecologic/obstetric causes of pelvic pain are easily diagnosed on ultrasound examination. Since the clinical presentation of gynecologic causes of pelvic pain overlaps with gastrointestinal and genitourinary pathology, referral to CT or MRI, especially in pregnant patients, should be considered if the US examination is nondiagnostic. © 2011 Elsevier Inc. Source

Staedtke V.,Ludwig Center for Cancer Genetics and Therapeutics | Staedtke V.,The Johns Hopkins Medical Institutes | Roberts N.J.,Ludwig Center for Cancer Genetics and Therapeutics | Roberts N.J.,Johns Hopkins Medical Institutions | And 2 more authors.
Genes and Diseases | Year: 2016

The attenuated anaerobic bacterium Clostridium novyi-NT (C. novyi-NT) is known for its ability to precisely germinate in and eradicate treatment-resistant hypoxic tumors in various experimental animal models and spontaneously occurring canine sarcomas. In this article, we review the therapeutic and toxicologic aspects of C. novyi-NT therapy, key challenges and limitations, and promising strategies to optimize its performance via recombinant DNA technology and immunotherapeutic approaches, to establish C. novyi-NT as an essential tool in cancer therapy. © 2016 Chongqing Medical University. Source

Pendleton C.,The Johns Hopkins Medical Institutes | Li Q.,The Johns Hopkins Medical Institutes | Chesler D.A.,The Johns Hopkins Medical Institutes | Yuan K.,The Johns Hopkins Medical Institutes | And 2 more authors.
PLoS ONE | Year: 2013

Introduction: Glioblastoma is the most common primary malignant brain tumor, and is refractory to surgical resection, radiation, and chemotherapy. Human mesenchymal stem cells (hMSC) may be harvested from bone marrow (BMSC) and adipose (AMSC) tissue. These cells are a promising avenue of investigation for the delivery of adjuvant therapies. Despite extensive research into putative mechanisms for the tumor tropism of MSCs, there remains no direct comparison of the efficacy and specificity of AMSC and BMSC tropism towards glioma. Methods: Under an IRB-approved protocol, intraoperative human Adipose MSCs (hAMSCs) were established and characterized for cell surface markers of mesenchymal stem cell origin in conjunction with the potential for tri-lineage differentiation (adipogenic, chondrogenic, and osteogenic). Validated experimental hAMSCs were compared to commercially derived hBMSCs (Lonza) and hAMSCs (Invitrogen) for growth responsiveness and glioma tropism in response to glioma conditioned media obtained from primary glioma neurosphere cultures. Results: Commercial and primary culture AMSCs and commercial BMSCs demonstrated no statistically significant difference in their migration towards glioma conditioned media in vitro. There was statistically significant difference in the proliferation rate of both commercial AMSCs and BMSCs as compared to primary culture AMSCs, suggesting primary cultures have a slower growth rate than commercially available cell lines. Conclusions: Adipose- and bone marrow-derived mesenchymal stem cells have similar in vitro glioma tropism. Given the well-documented ability to harvest larger numbers of AMSCs under local anesthesia, adipose tissue may provide a more efficient source of MSCs for research and clinical applications, while minimizing patient morbidity during cell harvesting. © 2013 Pendleton et al. Source

Discover hidden collaborations