Monitoring the protective effects of minocycline treatment with radiolabeled annexin V in an experimental model of focal cerebral ischemia.

Minocycline is an antibiotic now recognized to have antiapoptotic and antiinflammatory properties. Because of these properties, minocycline may be of benefit in reducing neuronal apoptosis from ischemia and subsequent postischemic inflammation if administered soon after a stroke. We now explore the feasibility of using (99m)Tc-annexin V, an in vivo marker of apoptosis, with SPECT to monitor the antiapoptotic effects of minocycline therapy. METHODS: CB6/F1 adult male mice underwent unilateral distal middle cerebral artery occlusion (dMCA) occlusion and were imaged and sacrificed at 1, 3, 7, or 30 d after injury. Animals were given minocycline (or vehicle) 30 min and 12 h after dMCA occlusion and then given 22.5 mg/kg twice daily for up to 7 d. Before imaging, behavioral tests were performed to evaluate the neurologic function. After imaging, brains were collected for histology and assessed for the degree of apoptosis and microglial activation. RESULTS: (99m)Tc-Annexin V uptake in injured hemispheres was significantly decreased 2- to 3-fold by minocycline at all time points. Minocyline reduced infarct size as seen histologically and improved behavioral indices as late as 30 d. Infarct volume as seen histologically correlated with radiolabeled annexin V uptake seen by SPECT. In situ fluorescent microscopy demonstrated that annexin V bound primarily to neurons at 1 and 3 d, with a shift toward microglia by 7 and 30 d. CONCLUSION: We found that minocycline significantly reduces neuronal apoptosis and infarct size and improves neurologic outcome in mice after acute focal cortical ischemia.     

Galaxy: a platform for interactive large-scale genome analysis

Accessing and analyzing the exponentially expanding genomic sequence and functional data pose a challenge for biomedical researchers. Here we describe an interactive system, Galaxy, that combines the power of existing genome annotation databases with a simple Web portal to enable users to search remote resources, combine data from independent queries, and visualize the results. The heart of Galaxy is a flexible history system that stores the queries from each user; performs operations such as intersections, unions, and subtractions; and links to other computational tools. Galaxy can be accessed at http://g2.bx.psu.edu.     

Computed tomography as an adjunct to ultrasound in the diagnosis of acute acalculous cholecystitis

The sonographic and computed tomographic (CT) findings were reviewed in 17 patients with acute acalculous cholecystitis (AAC) over a 6-year period from 1984 to 1989. Of the six patients in whom both ultrasound and CT were performed, CT revealed marked gallbladder (GB) wall abnormalities, including perforation, and pericholecystic fluid collections in five patients not demonstrated by sonography. Of the total group, five patients had GB wall thicknesses of 3 mm (normal) at pathologic examination, which demonstrated a spectrum of disease ranging from acute hemorrhagic/necrotizing, to gangrenous acalculous cholecystitis with perforation. Sonography was falsely negative or significantly underestimated the severity of AAC in seven of the 13 patients examined by sonography. CT because of its superior ability to assess pericholecystic inflammation may provide additional diagnostic information even after a thorough sonographic study in cases of AAC.     

Biomarkers for heart failure: small molecules with high clinical relevance

Heart failure (HF) is a rising epidemic due to the ageing population and progress in all areas of medicine. Thus, research efforts are made to ensure a timely diagnosis, to improve prognosis and treatment of the disease and to facilitate risk prediction at the population level. Because of their noninvasive determination with mostly high sensitivity and accuracy, circulating blood biomarkers are becoming increasingly important for daily clinical practice. Natriuretic peptides, especially B‐type natriuretic peptide (BNP), N‐terminal pro‐B‐type natriuretic peptide (Nt‐proBNP) and midregional pro‐atrial natriuretic peptide (MR‐proANP) and cardiac troponins are established blood biomarkers in HF diagnosis and prognosis of HF‐related outcomes. Inflammatory molecules as C‐reactive protein (CRP) may have added value in anti‐inflammatory therapy guidance. Next‐generation biomarkers including soluble source of tumorigenicity 2 (sST2), growth differentiation factor‐15 (GDF‐15), galectin‐3 (Gal‐3) and diverse microribonucleic acids (miRNAs) may have additional benefit in assessment of cardiac remodeling or differentiation of HF subtypes. Multimarker approaches containing different combinations of established and novel biomarkers might improve HF risk prediction at the population level once they are used on top of clinical variables.     

Aortic root dimensions as a correlate for aortic regurgitation’s severity

The International Journal of Cardiovascular Imaging - To evaluate the prevalence of aortic regurgitation (AR) and associations between the individual aortic root components and AR severity in the...     

Influence of impaired fasting glucose on the incidence and prognosis of atherosclerosis in various vascular regions

Patients with cardiovascular disease have a poorer diagnosis if they are diabetic. The risk for cardiovascular events is already increased in individuals with impaired fasting glucose (IFG). The aim of this study was to evaluate the impact of diabetes mellitus (DM) and IFG on the incidence of atherosclerotic manifestations and on the long-term prognosis of patients with atherosclerosis in various vascular regions. METHODS: In a prospective study we included 906 patients (72.5% men, mean age 62 +/- 9 years) preceding heart catheterization. All patients were evaluated for the presence of peripheral stenosis by carotid duplex sonography (pathologic: stenosis >50%) and evaluation of the ankle-brachial index (pathologic <0.9). Blood samples were drawn from each subject after an overnight fasting period and serum glucose was evaluated. RESULTS: Patients were compared with regard to the presence of DM (known DMor fasting glucose > or =126 mg/dL, N = 283, 31.2%) or IFG (fasting glucose >110 and <126 mg/dL, N = 89, 9.8%). Patients with IFG and DM had a higher prevalence of atherosclerotic manifestations in the coronary, carotid and peripheral vessels. Diabetics had the highest prevalence of atherosclerotic manifestations in multiple vascular regions (=advanced atherosclerosis). Cardiovascular events (death, myocardial infarction and stroke) after a median follow-up of 4.1 years were evaluated in 901 patients (99.4%). Presence of IFG and DM significantly increased the incidence of cardiovascular events (event rate: no DM 10.9%, IFG 13.6%, DM 23.4%, P < 0.0001). Moreover, patients with advanced atherosclerosis suffered significantly more often from cardiovascular events (event rate: no stenosis 4.1%, coronary artery disease without peripheral stenosis 9.7%, advanced atherosclerosis 23.9%). Prognosis was worst in patients with DM and advanced atherosclerosis with an event rate of 35%.Patients with cardiovascular disease have a poorer prognosis if they are diabetic. The risk for cardiovascular events is already increased in individuals with impaired fasting glucose (IFG). The aim of this study was to evaluate the impact of diabetes mellitus (DM) and IFG on the incidence of atherosclerotic manifestations and on the long-term prognosis of patients with atherosclerosis in various vascular regions.     

Comprehensive analysis of dural ectasia in 150 patients with a causative FBN1 mutation

The purpose of this study was to perform a comprehensive study of dural ectasia (DE) related to FBN1 mutations. We performed a database analysis of two German metropolitan regions of 150 patients (68 men, 82 women; mean age 35 ± 16 years). All patients had a FBN1 mutation and underwent dural magnetic resonance imaging. Age was <16 years in 20, 16–25 in 27, 26–35 in 67, and >35 in 36 patients. Prevalence of dural ectasia was 89% with criteria of Oosterhof and Habermann, 83% with Fattori, 78% with Lundby, and 59% with Ahn. DE was less frequent in patients <16 years with Ahn and Fattori. DE related to skeletal manifestations with all criteria, to aortic Z‐scores and mitral valve prolapse with criteria of Habermann and Lundby, and to age with criteria of Fattori. The Fattori‐grade of DE increased with age, aortic Z‐scores, and skeletal score points. There was no consistent relationship of DE with any type of FBN1 mutation. DE is frequent in patients with FBN1 mutations irrespective of age and its severity increases during life. Criteria of Oosterhof and Habermann yielded most consistent diagnostic results. DE relates to skeletal involvement, aortic Z‐scores, and mitral valve prolapse.