Glomerular sieving of anionic and neutral bovine albumins in proteinuric rats

Glomerular sieving of anionic and neutral bovine albumins in proteinuric rats. To characterize the defect in glomerular permeability leading to albuminuria in rats made nephrotic acutely by infusion of hexadimethrine (HDM) or chronically by administration of Adriamycin® (doxorubicin) (Adria), we developed and validated a tissue accumulation method for simultaneous determination of the glomerular sieving coefficients (GSC) of anionic 131I-labeled bovine albumin (BSA-pI 4.9) and 125I-labeled charge-modified neutral BSA (nBSA-pI 7.5 to 8.0). Total filtered marker was calculated by adding marker excreted in the urine to that filtered but reabsorbed by the tubules. The latter was determined by subtracting interstitial marker present in the left kidney, rendered non-filtering by ureteral ligation during mannitol diuresis, from the total marker accumulating within the right, filtering kidney. Experiments showed that markers circulated and were excreted intact and were neither degraded nor deiodinated during the period of the clearance studies.In control animals the GSC of nBSA (0.026 ± 0.004) greatly exceeded that of BSA (0.0006 ± 0.0002), demonstrating the normal charge dependence of permeability. Both proteinuric groups had marked increases in the GSC of BSA (HDM: 0.021 ± 0.005; Adria: 0.025 ± 0.004), which correlated with appearance of rat albumin in their urine. HDM rats also had a twofold increase in the GSC of nBSA (0.049 ± 0.005), indicating alteration of the size dependence of permeability. The absolute increase of GSC of BSA and nBSA was similar, suggesting that albuminuria resulted from appearance of new “pores” in the glomerular filter that were not charge selective for proteins of the size of albumin. Thus, infusion of HDM, which binds to and neutralizes GBM anions, appears to produce albuminuria by inducing a structural change in the glomerular filter. Conversely, Adria rats had no significant increase in the GSC of nBSA (0.031 ± 0.005), indicating no significant change in the size dependence of permeability for proteins of the size of albumin. In these animals, the GSC of the anionic BSA approached that of the neutral nBSA, indicating that Adriamycin induces albuminuria by markedly reducing the normal charge dependence of permeability

The Multiple Sclerosis Inventory of Cognition for Adolescents (MUSICADO): A brief screening instrument to assess cognitive dysfunction, fatigue and loss of health-related quality of life in pediatric-onset multiple sclerosis

Objective: Screening for cognitive impairment (CI), fatigue and also Health-related quality of life (HRQoL) in patients with pediatric-onset multiple sclerosis (POMS) is of utmost importance in clinical practice. The aim of this study was to establish a new and validated pediatric screening tool MUSICADO that is easy to use and time economical. Methods: 106 patients with POMS aged 12-18 years and 210 healthy controls (HCs) stratified for age and education underwent neuropsychological testing including a screening test Multiple Sclerosis Inventory of Cognition for adults and 8 standardized cognitive tests and established scales to assess fatigue and HRQoL. Results: The phonemic verbal fluency task (RWT s-words), the Trail Making Test A (TMTA), and the Digit Span Forward discriminated significantly between patients and HCs (p = 0.000, respectively) and showed the highest proportion of test failure in patients 24.5%, 17.9%; 15.1%, respectively). Therefore, they were put together to form the cognitive part of the MUSICADO. After applying a scoring algorithm with balanced weighting of the subtests and age and education correction and a cut-off score for impairment, 35.8% of patients were categorized to be cognitively impaired (specificity: 88.6%). Fatigue was detected in 37.1% of the patients (specificity: 94.0%) and loss of HRQoL in 41.8% (specificity 95.7%) with the screening version, respectively. Conclusion: The MUSICADO is a newly designed brief and easy to use screening test to help to early identify CI, fatigue, and loss of HRQoL in patients with POMS as cut scores are provided for all three items. Further studies will have to show its usability in independent samples of patients with POMS. (C) 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved

Fatigue and depression predict health-related quality of life in patients with pediatric-onset multiple sclerosis

Background: Fatigue, depression and loss in health-related quality of life (HRQoL) have been reported to occur in a substantial amount of patients with pediatric-onset MS (POMS). This study aims to evaluate depression, fatigue and HRQoL and its relationship in a cohort of patients with POMS and matched healthy controls (HCs). Methods: In a multicenter cross-sectional study, Beck Depression Inventory II, Depressionstest fur Kinder, the Pediatric Quality of Life Inventory (PedsQL (TM)) 4.0 Generic Core Scale and the PedsQL (TM) Multidimensional Fatigue Scale were performed. Results: In a cohort of 106 patients with POMS and 210 matched HCs, patients were significantly more often depressed (21.7% vs. 11.4%, p = 0.014) experienced greater fatigue (40.6% vs. 17.3%, p < 0.001) and a greater loss of HRQoL (43.4% vs. 15%, p < 0.001) than controls. Depression predicted 51.8% of variance of fatigue. Fatigue was also predicted by female gender. Loss of HRQoL was predicted by EDSS, depression and fatigue. Depression and fatigue together explained 67.7% of variance of HRQoL. Conclusion: Patients with POMS are at a significant increased risk for depression, fatigue and loss of HRQoL. Furthermore, fatigue and depression significantly predict reduced HRQoL in POMS, suggesting that testing for these symptoms and early therapy is of utmost importance in all patients with POMS