• Aortic Calcification and Femoral Bone Density Are Independently Associated with Left Ventricular Mass in Patients with Chronic Kidney Disease

      Chue, Colin D.; Wall, Nadezhda A.; Crabtree, Nicola J.; Zehnder, Daniel; Moody, William E.; Edwards, Nicola C.; Steeds, Richard P.; Townend, Jonathan N.; Ferro, Charles J.; Shi, Xing-Ming; et al. (2012-06-18)
      Background: Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a cross-sectional observational study.
    • Diagnosis and management of Crohn's disease.

      Wilkins, Thad; Jarvis, Kathryn; Patel, Jigneshkumar; Department of Family Medicine (2011-12-15)
      Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract at any point from the mouth to the rectum. Patients may experience diarrhea, abdominal pain, fever, weight loss, abdominal masses, and anemia. Extraintestinal manifestations of Crohn's disease include osteoporosis, inflammatory arthropathies, scleritis, nephrolithiasis, cholelithiasis, and erythema nodosum. Acute phase reactants, such as C-reactive protein level and erythrocyte sedimentation rate, are often increased with inflammation and may correlate with disease activity. Levels of vitamin B12, folate, albumin, prealbumin, and vitamin D can help assess nutritional status. Colonoscopy with ileoscopy, capsule endoscopy, computed tomography enterography, and small bowel follow-through are often used to diagnose Crohn's disease. Ultrasonography, computed axial tomography, scintigraphy, and magnetic resonance imaging can assess for extraintestinal manifestations or complications (e.g., abscess, perforation). Mesalamine products are often used for the medical management of mild to moderate colonic Crohn's disease. Antibiotics (e.g., metronidazole, fluoroquinolones) are often used for treatment. Patients with moderate to severe Crohn's disease are treated with corticosteroids, azathioprine, 6-mercaptopurine, or anti-tumor necrosis factor agents (e.g., infliximab, adalimumab). Severe disease may require emergent hospitalization and a multidisciplinary approach with a family physician, gastroenterologist, and surgeon.
    • Diagnostic criteria and severity assessment of acute cholecystitis: Tokyo Guidelines.

      Hirota, Masahiko; Takada, Tadahiro; Kawarada, Yoshifumi; Nimura, Yuji; Miura, Fumihiko; Hirata, Koichi; Mayumi, Toshihiko; Yoshida, Masahiro; Strasberg, Steven M; Pitt, Henry A; et al. (2007-01-25)
      The aim of this article is to propose new criteria for the diagnosis and severity assessment of acute cholecystitis, based on a systematic review of the literature and a consensus of experts. A working group reviewed articles with regard to the diagnosis and treatment of acute cholecystitis and extracted the best current available evidence. In addition to the evidence and face-to-face discussions, domestic consensus meetings were held by the experts in order to assess the results. A provisional outcome statement regarding the diagnostic criteria and criteria for severity assessment was discussed and finalized during an International Consensus Meeting held in Tokyo 2006. Patients exhibiting one of the local signs of inflammation, such as Murphy's sign, or a mass, pain or tenderness in the right upper quadrant, as well as one of the systemic signs of inflammation, such as fever, elevated white blood cell count, and elevated C-reactive protein level, are diagnosed as having acute cholecystitis. Patients in whom suspected clinical findings are confirmed by diagnostic imaging are also diagnosed with acute cholecystitis. The severity of acute cholecystitis is classified into three grades, mild (grade I), moderate (grade II), and severe (grade III). Grade I (mild acute cholecystitis) is defined as acute cholecystitis in a patient with no organ dysfunction and limited disease in the gallbladder, making cholecystectomy a low-risk procedure. Grade II (moderate acute cholecystitis) is associated with no organ dysfunction but there is extensive disease in the gallbladder, resulting in difficulty in safely performing a cholecystectomy. Grade II disease is usually characterized by an elevated white blood cell count; a palpable, tender mass in the right upper abdominal quadrant; disease duration of more than 72 h; and imaging studies indicating significant inflammatory changes in the gallbladder. Grade III (severe acute cholecystitis) is defined as acute cholecystitis with organ dysfunction.
    • HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent

      Qiao, Jingjuan; Li, Shunyi; Wei, Lixia; Jiang, Jie; Long, Robert; Mao, Hui; Wei, Ling; Wang, Liya; Yang, Hua; Grossniklaus, Hans E.; et al. (2011-03-24)
      The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomarker for various cancer types and a drug target for anti-cancer therapies. This multimodal HER20targeted MR imaging probe integrates a de novo designed protein contrast agent with a high affinity HER2 affibody and a near IR fluorescent dye. Our probe can differentially monitor tumors with different expression levels of HER2 in both human cell lines and xenograft mice models. In addition to its 100-fold higher dose efficiency compared to clinically approved non-targeting contrast agent DTPA, our developed agent also exhibits advantages in crossing the endothelial boundary, tissue distribution, and tumor tissue retention over reported contrast agents as demonstrated by even distribution of the imaging probe across the entire tumor mass. This contrast agent will provide a powerful tool for quantitative assessment of molecular markers, and improved resolution for diagnosis, prognosis and drug discovery.
    • Impact of Myeloid Cell NF-κB Signaling on Glioblastoma Growth

      Venugopal, Natasha; Howard, Shelby; Achyut, Bhagelu; Jain, Meenu; Arbab, Ali; Bradford, Jennifer W.; Department of Biological Sciences (2017-03)
      Cancer consists of malignant tumor cells as well as supporting, non-cancerous cells that make up the tumor stroma. Tumor-associated macrophages (TAMs), a critical component of the stroma, can be present in very large numbers in a variety of cancers, and can lead to tumor progression through promotion of tumor inflammation, angiogenesis, invasion, and metastasis. Canonical nuclear factor-kappaB (NF-κB) pathway activity is very important in normal immune function, synaptic plasticity, and memory, and aberrant NF-κB activity is associated with autoimmune disease, and importantly, cancer. Previous studies have been reported about the importance of tumor cell associated NF-κB signaling in cancers. As myeloid cell NF-κB signaling may also be important in promoting cancers, we have been utilizing the p65fl/fl/LysMCre transgenic animal model, which lacks p65 protein in cells of the myeloid lineage, to study the impact of myeloid cell derived NF-κB signaling in glioblastoma (GBM), an extremely aggressive brain cancer. This transgenic model has a very efficient deletion of p65 protein and drastically reduced NF-κB signaling in bone marrow derived macrophages (BMDMs), but brain residing microglia do not have significantly lower p65 levels as compared to control microglia. Even with this finding, p65fl/fl/LysMCre mice implanted with syngeneic GBM cells have significantly reduced GBM tumor burden than LysMCre control mice, as measured by magnetic resonance imaging. This result underscores the potential importance of bone marrow cells that migrate to the tumor site and significantly contribute to GBM growth. This work also indicates the potential benefits of targeting myeloid specific NF-κB signaling in GBM patients.
    • In vivo MRI Characterization of Progressive Cardiac Dysfunction in the mdx Mouse Model of Muscular Dystrophy

      Stuckey, Daniel J.; Carr, Carolyn A.; Camelliti, Patrizia; Tyler, Damian J.; Davies, Kay E.; Clarke, Kieran; McNeil, Paul L.; Department of Cellular Biology and Anatomy; College of Graduate Studies (2012-01-3)
      Aims: The mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs in muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant in vivo MRI techniques to identify early markers of cardiac dysfunction and follow disease progression in the hearts of mdx mice.
    • Open-magnet MR defaecography compared with evacuation proctography in the diagnosis and management of patients with rectal intussusception

      Ahn, Elizabeth; Davila, Alec; Heneidi, Saleh; Mohamed, Mohamed; Rahim, Tayeb; Thakkar, Nancy (2015-03-09)
      For patients with rectal intussusception, will the use of open-magnet magnetic resonance (MR) defaecography in addition to evacuation proctography (EP) result in better diagnosis and management?