Citations

Until recently, neuromyelitis optica (NMO) was considered to be a sub-type of multiple sclerosis (MS), which has a strong predilection for Caucasian populations, whereas NMO is more frequent in non-Caucasian individuals. The objective of this study was to compare the HLA-DRB profile in Brazilian Mulatto patients with NMO spectrum disorders (NMOSDs) with that observed for Mulatto MS patients and healthy Mulatto controls. Twenty seven NMOSD patients (20 women), all seropositive for NMO-IgG, 29 MS patients and 28 Mulatto healthy blood donors were evaluated for HLA-DRB allele groups. HLA-DRB1*03 allele group was overrepresented in NMO patients compared with healthy controls (p = 0.0401; OR = 3.23, 95%CI: 1.07—9.82). In contrast, the HLA-DRB1*15 allele group was overrepresented in Brazilian MS patients (OR = 15.89, 95%CI: 3.51—71.85; p < 0.0001). DRB3 was overrepresented in NMO (p = 0.0064), and DRB5 overrepresented in MS patients (p = 0.0001). The low frequency of HLA-DRB1*15 alleles was associated with the presence of long and central cord lesions at magnetic resonance. In addition, DRB1*15 alleles were associated with the fulfillment of the Barkhof criteria. In conclusion, these results indicate that the DRB profile of NMO patients is different from that observed for MS patients, further corroborating the distinction between NMO and MS.

Background Tightness of the posteroinferior capsule is assumed to be the cause of internal rotation loss in baseball pitchers. Although the relationship between posterior capsule and subacromial impingement has been recognized, this relationship during the baseball-pitching motion is unclear. Hypothesis Contact pressure during baseball-pitching motion increases with posterior capsule tightness. Study Design Controlled laboratory study. Methods Eight fresh-frozen shoulders were used. The peak contact pressure and area on the coracoacromial arch were measured on a custom-designed shoulder experimental device capable of 6 degrees of freedom motion. Simultaneously, the sites of peak pressure on the coracoacromial arch and humerus were observed from various angles. The posteroinferior capsule tightness was simulated by plicating the capsule in the region from 6 to 8 o'clock. The static testing positions correlated to the early cocking, late cocking, acceleration, deceleration, and follow-through phases of the pitching motion. Results The peak contact pressure during the follow-through phase (0.63 ± 0.50 MPa) significantly increased with posteroinferior capsule tightness (1.00 ± 0.65 MPa) (P = .014). Additionally, the contact area on the coracoacromial ligament during the follow-through phase (0.98 ± 0.67 cm2) significantly increased with posteroinferior capsule tightness (1.47 ± 0.91 cm 2) (P < .001). The site of the peak contact pressure did not change between the 2 conditions. Conclusion Our findings demonstrate that posteroinferior capsule tightness leads to higher contact pressure under the subacromial arch and increased contact area, particularly on the coracoacromial ligament during the follow-through phase. Clinical Relevance This tightness may affect risk of injury of the rotator cuff and its surrounding tissues by increasing subacromial contact during pitching.

Cutaneous sensory nerve-mediated vasodilation is an important component of normal microvascular responsiveness to thermal and nonthermal stimuli. Since both neural and microvascular function can be impaired in type 2 diabetes mellitus (T2DM), we tested the hypothesis that local sensory nerve-mediated vasodilation during nonpainful local warming of the skin is less in T2DM compared with healthy controls (C) matched for age and body size. The rapid vasodilation during the first ∼5 min of this local warming (“initial peak”) was previously shown to rely primarily on local sensory nerves. We measured skin blood flow in T2DM and C subjects ( n = 7 in each group) at baseline and during 35 min of local warming of the skin to 42°C at two sites on the ventral forearm. One site was pretreated with 4% lidocaine (LIDO) to block local sensory innervation. During local warming, cutaneous vascular conductance (CVC) during the initial peak was not different between groups, either at the untreated site [T2DM 75 ± 2 vs. C 81 ± 6% of maximum CVC (%maxCVC); P > 0.05] or at the LIDO site (T2DM 63 ± 7 vs. C 64 ± 6%maxCVC; P > 0.05). The difference between untreated and LIDO sites (sensory nerve contribution) was also similar between groups (T2DM 13 ± 5 vs. C 18 ± 5%maxCVC; P > 0.05) and was smaller with LIDO than was previously shown with other local anesthetics. Our results suggest that relatively healthy individuals with T2DM do not exhibit impairments in local sensory nerve vasodilation during thermal stimulation compared with controls of similar age and body size.

Abstract Background: We report the development of a novel high-sensitivity cardiac troponin T (hs-cTnT) assay, a modification of the Roche fourth-generation cTnT assay, and validation of the analytical performance of this assay. Methods: Validation included testing of analytical sensitivity, specificity, interferences, and precision. We established the 99th percentile cutoff from healthy reference populations (n = 616). In addition, we studied differences in time to a positive result when using serial measurements of hs-cTnT vs cTnT in patients with a confirmed diagnosis of non-ST elevation myocardial infarction (non-STEMI). Results: The hs-cTnT assay had an analytical range from 3 to 10 000 ng/L. At the 99th percentile value of 13.5 ng/L, the CV was 9% using the Elecsys® 2010 analyzer. The assay was specific for cTnT without interferences from human cTnI or cTnC, skeletal muscle TnT, or hemoglobin concentrations up to 1000 mg/L, above which falsely lower values would be expected. When the assay was evaluated clinically, a hs-cTnT higher than the 99th percentile concentration identified a significantly higher number of patients with non-STEMI on presentation (45 vs 20 patients, P = 0.0004) compared with cTnT, and a final diagnosis of non-STEMI was made in 9 additional patients (55 vs 46 patients, P = 0.23) after serial sampling. Time to diagnosis was significantly shorter using hs-cTnT compared with cTnT [mean 71.5 (SD 108.7) min vs 246.9 (82.0) min, respectively; P &lt; 0.01]. Conclusions: The analytical performance of hs-cTnT complies with the ESC-ACCF-AHA-WHF Global Task Force recommendations for use in the diagnosis of MI.

Abstract Background: The measurement of multiple protein biomarkers may refine risk stratification in clinical settings. This concept has stimulated development of multiplexed immunoassay platforms that provide multiple, parallel protein measurements on the same specimen. Content: We provide an overview of antibody-based multiplexed immunoassay platforms and discuss technical and operational challenges. Multiplexed immunoassays use traditional immunoassay principles in which high-affinity capture ligands are immobilized in parallel arrays in either planar format or on microspheres in suspension. Development of multiplexed immunoassays requires rigorous validation of assay configuration and analytical performance to minimize assay imprecision and inaccuracy. Challenges associated with multiplex configuration include selection and immobilization of capture ligands, calibration, interference between antibodies and proteins and assay diluents, and compatibility of assay limits of quantification. We discuss potential solutions to these challenges. Criteria for assessing analytical multiplex assay performance include the range of linearity, analytical specificity, recovery, and comparison to a quality reference method. Quality control materials are not well developed for multiplexed protein immunoassays, and algorithms for interpreting multiplex quality control data are needed. Summary: Technical and operational challenges have hindered implementation of multiplexed assays in clinical settings. Formal procedures that guide multiplex assay configuration, analytical validation, and quality control are needed before broad application of multiplexed arrays can occur in the in vitro diagnostic market.