Effect of interleukin-1 antagonists on the quality of life in familial Mediterranean fever patients

Clinical Rheumatology - Familial Mediterranean fever (FMF) patients suffer from chronic complications of disease such as AA amyloidosis, chronic arthritis, and spondylitis. Reduced quality of life...     

Magnetic resonance imaging evaluation of renal structure and function related to disease: technical review of image acquisition, postprocessing, and mathematical modeling steps

Kidney disease represents a leading cause of morbidity, with high healthcare costs. The existing methods used to evaluate renal function include measures of glomerular filtration rate (GFR), yet the clinical methods are generally inaccurate and poorly reproducible. A method that improves measures of renal function as part of a comprehensive examination that also evaluates renal structure represents an important unmet clinical need. Use of dynamic contrast-enhanced magnetic resonance imaging (MRI) for the evaluation of renal function has been undergoing development by several groups. The methodology has been referred to as MR Urography (MRU) or MR Nephro-urography (MRNU). MRU/MRNU shows promise for providing new insights into the evaluation of renal structure and function in relation to important disease processes, including urinary obstruction and in relation to renal transplantation. MRU/MRNU generally requires consideration of imaging acquisition technique, image postprocessing strategies, and subsequent kinetic mathematical modeling of the data in reference to specific physiological renal processes, such as renal blood flow and GFR. Here we review the specifics of proposed methods in light of the overall strengths and limitations of each of these strategies. The overall objective is to provide a roadmap for future developments in this evolving field of novel MRI applications.     

Co-morbidity of Sanfilippo Syndrome type C and d-2-hydroxyglutaric aciduria

Journal of Neurology -     

Multicenter Evaluation of Bactec MGIT 960 System for Second-Line Drug Susceptibility Testing of Mycobacterium tuberculosis Complex

The Bactec MGIT 960 system for testing susceptibility to second-line drugs was evaluated with 117 clinical strains in a multicenter study. The four drugs studied were levofloxacin, amikacin, capreomycin, and ethionamide. The critical concentration established for levofloxacin and amikacin was 1.5 μg/ml, that established for capreomycin was 3.0 μg/ml, and that established for ethionamide was 5.0 μg/ml. The overall level of agreement between the agar proportion method and the MGIT 960 system was 96.4%, and the levels of agreement for the individuals drugs were 99.1% for levofloxacin, 100% for amikacin, 97.4% for capreomycin, and 88.9% for ethionamide. The rate of reproducibility of the drug susceptibility testing results between the participating laboratories was 99.5%.The increase in the incidence of multidrug-resistant tuberculosis (MDR TB) and the emergence of extensively drug-resistant tuberculosis present tremendous challenges to the global efforts to combat tuberculosis (1, 5, 16, 21). Rapid methods enabling accurate susceptibility testing of first-line and second-line drugs are critical for the early diagnosis of MDR TB and extensively drug-resistant tuberculosis and the initiation of effective regimens. Various drug susceptibility testing (DST) methods that use solid media, including the agar proportion method (AP) and other methods, have the drawback of prolonged turnaround times (TATs). The World Health Organization and the U.S. Centers for Disease Control and Prevention have recommended the use of liquid culture systems for the diagnosis of tuberculosis and DST to improve TATs (22, 25). The Bactec 460 (Becton Dickinson Diagnostic Systems, Sparks, MD), a radiometric liquid system, provided an excellent alternative for testing of the susceptibilities of Mycobacterium tuberculosis complex (MTBC) isolates to streptomycin, isoniazid, rifampin (rifampicin), and ethambutol (SIRE) and to pyrazinamide (PZA) with improved TATs. The MGIT 960 liquid, nonradiometric SIRE DST (Becton Dickinson Diagnostic Systems), whose performance is comparable to that of the Bactec 460 system, has been commercially available since April 2002 (4, 20, 23). The Microbial Diseases Laboratory (MDL) of the California Department of Public Health implemented SIRE DST with the MGIT 960 system in 2004. With confidence in the SIRE DST with the MGIT 960 system, a study that used the same platform to test the susceptibilities of MTBC isolates to four classes of second-line drugs, levofloxacin (LVX), amikacin (AMK), capreomycin (CAP), and ethionamide (ETH), was initiated in November 2004. The study was conducted at two laboratories: MDL and the TB Reference Laboratory of the Veteran Affairs Medical Center (VA) in West Haven, CT. Here we report the results of the multicenter study, in which the critical concentrations of the test drugs were established, the performance of the MGIT 960 system was compared to that of AP, and the interlaboratory reproducibility of the method was evaluated.(Part of this work was presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, 2006, San Francisco, CA.)     

Sound conditioning protects hearing by activating the hypothalamic-pituitary-adrenal axis

Sound conditioning primes the auditory system to low levels of acoustic stimuli and reduces damage caused by a subsequent acoustic trauma. This priming activates the HPA axis resulting in the elevation of plasma corticosterone with a consequent upregulation of glucocorticoid receptors (GR) in the cochlea and the paraventricular nucleus (PVN) of the hypothalamus in the mouse. This protective effect is blocked by adrenalectomy or pharmacological treatment with RU486 + metyrapone. Sound conditioning prevents GR down-regulation induced by acoustic trauma and subsequently enhances GR activity in spiral ganglion neurons. Increased SRC-1 expression, triggered by sound conditioning, positively correlates with the upregulation of GR in the cochlea. These findings will help to define the cellular mechanisms responsible for protecting the auditory system from hearing loss by sound conditioning.