Injury among 1107 Canadian students with self-identified disabilities

PURPOSE: Students with disabilities are at risk for poor health outcomes; however, the causes and consequences of injury in this group are not well understood. The epidemiologies of injuries among students with and without disabilities were profiled and compared. METHODS: The cross-sectional, 2002 Health Behaviour in School-aged Children Survey, was administered to a representative sample of 7235 students (grades 6-10) from Canada. Students who reported at least one functional difficulty due to a health condition were classified as having a disability. Primary outcomes were: (i) Medically attended injury; (ii) multiple injuries, and (iii) serious injury experiences during a 12-month period. RESULTS: Some 16.3% of students reported a disability. Injuries were more common in students with disabilities compared to those without disabilities (67% vs. 51% annually, p < 0.01). Students with disabilities experienced 30% increases in the risk for medically attended injury, multiple injury, and serious injury as compared to their peers. Consistent and statistically significant associations (p < 0.05) were identified between different types of disability and all injury outcomes. CONCLUSIONS: Canadian students who report disabilities experience higher risks for injury than their peers, perhaps due to an inability to perceive and avoid environmental hazards. Injury prevention programmes are needed to address these unique risk profiles in order to prevent additional disability or secondary conditions.     

Role of Power Doppler sonography in evaluation of therapeutic response of the knee in juvenile rheumatoid arthritis

The objective is to study the role of power Doppler sonography (PDS) in assessment of therapeutic response in juvenile rheumatoid arthritis (JRA) of knee joint. Thirty patients (age range 3–11 years) of JRA with knee joint involvement were selected for this study. Clinical assessment and ultrasound was done on the same day and repeated at the end of second and sixth month of therapy. All patients received naproxen (15–20 mg/kg/day) for a period of 6 months. Total clinical score (TCS) was calculated as sum of scores of pain, articular swelling and functional impairment. PDS was performed and degree of vascularity was assessed and graded. Total USG score was obtained by adding sum of scores of synovial effusion, synovial thickening and PDS. Results were compared between the total clinical score and the total ultrasound score and between clinical groups at baseline, end of second month and end of sixth month. There were statistically significant differences between clinical and ultrasound indices and confirmed that PDS is more sensitive in detection and follow-up of clinically silent cases of JRA. PDS holds great promise for detection of active synovial inflammatory disease in sub-clinical cases of JRA and is useful in objective assessment of therapeutic response.     

Urine NGAL Predicts Severity of Acute Kidney Injury After Cardiac Surgery: A Prospective Study

Background and objectives: The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT analyzer®, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after CPB was tested.Design, setting, participants, & measurements: In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT® assay were highly correlated (r = 0.99). In a subsequent study, 196 children undergoing CPB were prospectively enrolled and serial urine NGAL measurements obtained by ARCHITECT® assay. The primary outcome was AKI, defined as a ≥50% increase in serum creatinine.Results: AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death.Conclusions: Accurate measurements of urine NGAL are obtained using the ARCHITECT® platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.Cardiopulmonary bypass (CPB) surgery is the most frequent major surgical procedure performed in hospitals worldwide, with well over a million operations undertaken each year in adults alone (1). Acute kidney injury (AKI), previously referred to as acute renal failure, is a frequent and serious complication encountered in 30% to 50% of subjects after CPB (2,3). AKI requiring dialysis occurs in up to 5% of these cases, in whom the mortality rate approaches 80%, and is the strongest independent risk factor for death after CPB, with an odds ratio of 7.9 (4). Even minor degrees of postoperative AKI, as manifest by only a 0.2 to 0.3 mg/dl rise in serum creatinine from baseline, predict a significant increase in short-term mortality (5,6). AKI after cardiac surgery is also associated with a number of adverse outcomes, including prolonged intensive care and hospital stay, dialysis dependency, diminished quality of life, and increased long-term mortality (7–9).Clinical investigations have identified several risk factors associated with the development of AKI after CPB, the majority related to either impaired renal perfusion or decreased renal reserve, and have resulted in the development of clinical scoring systems for the prediction of AKI (10–13). However, these tools have not been validated across medical centers, and have focused primarily on identifying the small number of high-risk, dialysis-requiring subjects. Concomitant advances in the basic sciences have illuminated the pathogenesis of AKI and have paved the way for successful therapeutic approaches in animal models (14). However, translational research efforts for the identification of effective therapeutic strategies in humans with AKI have yielded disappointing results (2,15). A major reason for the failure to find an effective treatment in patients is the paucity of early biomarkers for AKI, akin to troponins in acute myocardial disease (16). The availability of effective biomarkers may lead to improved efforts at ameliorating the course of AKI or preventing further renal injury. However, in current clinical practice, the gold standard for identification and classification of AKI is dependent on serial serum creatinine measurements (17), which are especially unreliable during acute changes in kidney function (15,16).We used a genome-wide interrogation strategy to identify kidney genes that are induced very early after AKI in animal models, whose protein products might serve as novel early biomarkers. We identified neutrophil gelatinase-associated lipocalin (NGAL) as one of the most upregulated genes in the kidney soon after ischemic injury (18–20). NGAL protein was also markedly induced in kidney tubule cells and easily detected in the plasma and urine in animal models of ischemic and nephrotoxic AKI (18–22). The expression of NGAL protein was also dramatically increased in kidney tubules of humans with ischemic, septic, and post-transplant AKI (23,24). Importantly, NGAL in the urine was found to be an early predictive biomarker of AKI in a variety of acute clinical settings (25). In a cohort of 20 subjects who developed AKI 2 to 3 d after cardiac surgery, urine NGAL measured by a research enzyme-linked immunosorbent assay (ELISA) was elevated within 2 to 6 h after CPB (16,26). Preliminary results using the research-based assay also suggest that urine NGAL measurements can predict AKI following contrast administration (27), kidney transplantation (28), hemolytic-uremic syndrome (29), lupus nephritis (30), and in critically ill subjects (31). The availability of a standardized clinical platform for NGAL measurements could revolutionize renal diagnostics, especially in intensive care situations (32). Therefore, the first objective of the present study was to determine whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT® analyzer, Abbott Diagnostics) correlates with the research-based assay. The second objective was to determine the utility of the standardized NGAL immunoassay as a predictive biomarker of AKI after CPB in a large prospective cohort.     

Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the Beaver Dam Eye Study

Age-related cataracts are one of the leading causes of visual impairment and blindness among the elderly worldwide. Among age-related cataracts, cortical opacities rank as the second most common type; however, little is known about their molecular pathogenesis or genetics. To identify susceptibility loci for cortical cataracts, we genotyped a subset of families (102 families; n = 224 sib pairs) from the Beaver Dam Eye Study and performed a model-free genome-wide linkage analysis for markers linked to a quantitative measure of cortical opacity. We obtained evidence for linkage at marker D1S1622 on chromosome 1p35 (P < 0.0002) and at marker D6S1053 on 6q12 (P < 0.00008) in the initial scan. Five additional regions on 1q31, 2p24, 2q11, 4q28, and 15q13 that are suggestive of linkage (P < or = 0.01 or logarithm of the likelihood ratio > or = 1.18) were observed. The region on chromosomes 6p12-q12 was selected for fine mapping, and the intermarker distance was reduced to 3 cM by adding 11 markers in the interval between D6S1017 and D6S1021. After fine mapping, significant evidence of linkage remained on chromosome 6p12-q12 at D6S1053 (P < 0.00005). The current genome scan for age-related cortical cataracts may lead to identification of novel genes, because few regions identified in the current scan have previously been implicated in congenital or age-related cataracts.     

Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2

Stimulation of a mutant angiotensin type 1A receptor (DRY/AAY) with angiotensin II (Ang II) or of a wild-type receptor with an Ang II analog ([sarcosine1,Ile4,Ile8]Ang II) fails to activate classical heterotrimeric G protein signaling but does lead to recruitment of beta-arrestin 2-GFP and activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) (maximum stimulation approximately 50% of wild type). This G protein-independent activation of mitogen-activated protein kinase is abolished by depletion of cellular beta-arrestin 2 but is unaffected by the PKC inhibitor Ro-31-8425. In parallel, stimulation of the wild-type angiotensin type 1A receptor with Ang II robustly stimulates ERK1/2 activation with approximately 60% of the response blocked by the PKC inhibitor (G protein dependent) and the rest of the response blocked by depletion of cellular beta-arrestin 2 by small interfering RNA (beta-arrestin dependent). These findings imply the existence of independent G protein- and beta-arrestin 2-mediated pathways leading to ERK1/2 activation and the existence of distinct "active" conformations of a seven-membrane-spanning receptor coupled to each.