Reliability of Classifying Multiple Sclerosis Disease Activity Using Magnetic Resonance Imaging in a Multiple Sclerosis Clinic.

Reliability of classifying multiple sclerosis disease activity using magnetic resonance imaging in a multiple sclerosis clinic.

JAMA Neurol. 2013 Mar 1; 70(3): 338-44
Erbayat Altay E, Fisher E, Jones SE, Hara-Cleaver C, Lee JC, Rudick RA

To assess the reliability of new magnetic resonance imaging (MRI) lesion counts by clinicians in a multiple sclerosis specialty clinic.An observational study.A multiple sclerosis specialty clinic.Eighty-five patients with multiple sclerosis participating in a National Institutes of Health–supported longitudinal study were included.Each patient had a brain MRI scan at entry and 6 months later using a standardized protocol.The number of new T2 lesions, newly enlarging T2 lesions, and gadolinium-enhancing lesions were measured on the 6-month MRI using a computer-based image analysis program for the original study. For this study, images were reanalyzed by an expert neuroradiologist and 3 clinician raters. The neuroradiologist evaluated the original image pairs; the clinicians evaluated image pairs that were modified to simulate clinical practice. New lesion counts were compared across raters, as was classification of patients as MRI active or inactive.Agreement on lesion counts was highest for gadolinium-enhancing lesions, intermediate for new T2 lesions, and poor for enlarging T2 lesions. In 18% to 25% of the cases, MRI activity was classified differently by the clinician raters compared with the neuroradiologist or computer program. Variability among the clinical raters for estimates of new T2 lesions was affected most strongly by the image modifications that simulated low image quality and different head position.Between-rater variability in new T2 lesion counts may be reduced by improved standardization of image acquisitions, but this approach may not be practical in most clinical environments. Ultimately, more reliable, robust, and accessible image analysis methods are needed for accurate multiple sclerosis disease-modifying drug monitoring and decision making in the routine clinic setting. HubMed – drug

Novel foam drug carrier is developed to treat urinary diseases.

Nanomedicine (Lond). 2013 Mar; 8(3): 327
Coaker H

HubMed – drug

New nanoscale engineering may allow improved drug delivery techniques.

Nanomedicine (Lond). 2013 Mar; 8(3): 326
Fitzpatrick S

HubMed – drug

Inhibitors of HIV-1 Reverse Transcriptase-Associated Ribonuclease H Activity.

Biology (Basel). 2012 Oct 19; 1(3): 521-541
Ilina T, Labarge K, Sarafianos SG, Ishima R, Parniak MA

HIV-1 enzyme reverse transcriptase (RT) is a major target for antiviral drug development, with over half of current FDA-approved therapeutics against HIV infection targeting the DNA polymerase activity of this enzyme. HIV-1 RT is a multifunctional enzyme that has RNA and DNA dependent polymerase activity, along with ribonuclease H (RNase H) activity. The latter is responsible for degradation of the viral genomic RNA template during first strand DNA synthesis to allow completion of reverse transcription and the viral dsDNA. While the RNase H activity of RT has been shown to be essential for virus infectivity, all currently used drugs directed at RT inhibit the polymerase activity of the enzyme; none target RNase H. In the last decade, the increasing prevalence of HIV variants resistant to clinically used antiretrovirals has stimulated the search for inhibitors directed at stages of HIV replication different than those targeted by current drugs. HIV RNase H is one such novel target and, over the past few years, significant progress has been made in identifying and characterizing new RNase H inhibitor pharmacophores. In this review we focus mainly on the most potent low micromolar potency compounds, as these provide logical bases for further development. We also discuss why HIV RNase H has been a difficult target for antiretroviral drug development. HubMed – drug