Citations

The vasodilator signals regulating muscle blood flow during exercise are unclear. We tested the hypothesis that in young adults leg muscle vasodilation during steady-state exercise would be reduced independently by sequential pharmacological inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) with NG-nitro-l-arginine methyl ester (l-NAME) and ketorolac, respectively. We tested a second hypothesis that NOS and COX inhibition would increase leg oxygen consumption (V̇o2) based on the reported inhibition of mitochondrial respiration by nitric oxide. In 13 young adults, we measured heart rate (ECG), blood pressure (femoral venous and arterial catheters), blood gases, and venous oxygen saturation (indwelling femoral venous oximeter) during prolonged (25 min) steady-state dynamic knee extension exercise (60 kick/min, 19 W). Leg blood flow (LBF) was determined by Doppler ultrasound of the femoral artery. Whole body V̇o2 was measured, and leg V̇o2 was calculated from blood gases and LBF. Resting intra-arterial infusions of acetylcholine (ACh) and nitroprusside (NTP) tested inhibitor efficacy. Leg vascular conductance (LVC) to ACh was reduced up to 53 ± 4% by l-NAME + ketorolac infusion, and the LVC responses to NTP were unaltered. Exercise increased LVC from 4 ± 1 to 33.1 ± 2 ml·min−1·mmHg−1 and tended to decrease after l-NAME infusion (31 ± 2 ml·min−1·mmHg−1, P = 0.09). With subsequent administration of ketorolac LVC decreased to 29.6 ± 2 ml·min−1·mmHg−1 ( P = 0.02; n = 9). While exercise continued, LVC returned to control values (33 ± 2 ml·min−1·mmHg−1) within 3 min, suggesting involvement of additional vasodilator mechanisms. In four additional subjects, LVC tended to decrease with l-NAME infusion alone ( P = 0.08) but did not demonstrate the transient recovery. Whole body and leg V̇o2 increased with exercise but were not altered by l-NAME or l-NAME + ketorolac. These data indicate a modest role for NOS- and COX-mediated vasodilation in the leg of exercising humans during prolonged steady-state exercise, which can be restored acutely. Furthermore, NOS and COX do not appear to influence muscle V̇o2 in untrained healthy young adults.

Purpose The purpose of this study was to document management strategies and complications relating to the use of anteromedial portals for elbow arthroscopy in a series of patients with subluxating or previously transposed ulnar nerves. Methods A review of 913 elbow arthroscopies showed that 59 elbows with a subluxating or previously transposed ulnar nerve required anterior compartment arthroscopic surgery. The patients with subluxating nerves had proximal anteromedial portals established by reducing and holding the nerve behind the epicondyle with a thumb while establishing or entering the portal. In cases of prior nerve transposition, the following techniques were used if, by palpation, localization of the ulnar nerve was considered to be (1) unequivocal, (2) equivocal, or (3) impossible: In group 1 (unequivocal) the proximal anteromedial portal was established in the normal antegrade fashion. In group 2 (equivocal) a 1‐cm incision was made at the planned proximal anteromedial portal site and blunt dissection down to the capsule was performed without identification of the nerve. In group 3 (impossible) a 2‐ to 4‐cm skin incision was made and the nerve was identified before placement of the portal. Results We found that 59 elbows in 56 patients had a subluxating ulnar nerve (31 elbows) or previous ulnar nerve transposition (28 elbows). The transposition had been subcutaneous in 21 and submuscular in 7. The proximal anteromedial portal was used in all but 3 cases (2 patients) of submuscular transposition that were early in the series. In those cases only 2 lateral portals were used for anterior compartment surgery. There were no operative ulnar nerve injuries related to the use of the proximal anteromedial portal. Conclusions Neither elbow arthroscopy nor specifically the use of the proximal anteromedial portal is contraindicated in patients with prior transposition or subluxation of the ulnar nerve. The management of the nerve can be based on the degree of certainty with which the nerve can be localized by palpation in the region of the planned portal. Level of Evidence Level IV, therapeutic case series.

Abstract The B cell-activating factor of the TNF family receptor (BAFF-R), encoded by the TNFRSF13C gene, is critically important for transitional B cell survival to maturity. Thus, ligation of BAFF-R by BAFF delivers a potent survival signal. Reports implicating the BAFF/BAFF-R signaling axis in the pathogenesis of autoimmune human diseases and B lineage malignancies have largely prompted studies focusing on BAFF expression; however, there is an equally critical need to better understand BAFF-R expression. Initial BAFF-R expression, although characterized in murine B cells, has not yet been reported in human B lymphopoiesis. In this study, we first demonstrate that BAFF-R expression is absent from early precursors and is acquired by bone marrow B cells newly expressing the BCR. We next focused on identifying the specific genomic region that controls BAFF-R expression in mature B cells (i.e., the TNFRSF13C promoter). To accomplish this, we used in silico tools examining interspecies genomic conservation in conjunction with reporter constructs transfected into malignant B and plasma cell lines. DNase protection assays using nuclear extracts from BAFF-R–expressing cells suggested potential regulatory sites, which allowed the generation of EMSA probes that bound NFs specific to BAFF-R–expressing cells. With a more stringent analysis of interspecies homology, these assays identified a site at which a single nucleotide substitution could distinctly impact promoter activity. Finally, chromatin immunoprecipitation assays revealed the in vivo binding of the specific transcription factor c-Rel to the most proximal genomic region, and c-Rel small interfering RNA transfections in BAFF-R–expressing lines demonstrated a coincident knockdown of both c-Rel and BAFF-R mRNA.

AbstractBackground: Glucose meter analytical performance criteria required for safe and effective management of patients on tight glycemic control (TGC) are not currently defined. We used simulation modeling to relate glucose meter performance characteristics to insulin dosing errors during TGC.Methods: We used 29 920 glucose values from patients on TGC at 1 institution to represent the expected distribution of glucose values during TGC, and we used 2 different simulation models to relate glucose meter analytical performance to insulin dosing error using these 29 920 initial glucose values and assuming 10%, 15%, or 20% total allowable error (TEa) criteria.Results: One-category insulin dosing errors were common under all error conditions. Two-category insulin dosing errors occurred more frequently when either 20% or 15% TEa was assumed compared with 10% total error. Dosing errors of 3 or more categories, those most likely to result in hypoglycemia and thus patient harm, occurred infrequently under all error conditions with the exception of 20% TEa.Conclusions: Glucose meter technologies that operate within a 15% total allowable error tolerance are unlikely to produce large (≥3-category) insulin dosing errors during TGC. Increasing performance to 10% TEa should reduce the frequency of 2-category insulin dosing errors, although additional studies are necessary to determine the clinical impact of such errors during TGC. Current criteria that allow 20% total allowable error in glucose meters may not be optimal for patient management during TGC.

Cardiovascular disease (CVD) has been the number one killer in the United States. It has long been recognized that a high percentage of all cardiovascular disease is associated with the hardening of arteries or arteriosclerosis. Several imaging techniques, including x-ray angiography, ultrasound, magnetic resonance imaging (MRI), etc., are available for imaging atherosclerotic arteries. Most imaging techniques measure luminal diameter, wall thickness and plaque volume. However, no current imaging methods can measure elasticity of the arterial wall. Pulse wave velocity (PWV) is a simple and robust method to measure arterial stiffness. However, PWV can not evaluate the local arterial stiffness. We have developed a novel ultrasound method for estimating local elasticity of arteries by the wave speed dispersion. In this paper, we present a method to measure the wave speed dispersion by resonance. Theory was developed to calculate the wave speed in cylindrical tubes. Experiments were done on a rubber tube. The resonance of the tube was generated by an air-coupled ultrasound transducer. The resonance frequency was measured by a laser vibrometer. Theoretical and experimental wave dispersions were compared. This method may be useful in characterizing the elastic properties of arterial samples where the wave speed dispersion can not be easily measured.

Abstract Genetic risk factors are important contributors to the development of colorectal cancer. Following the definition of a linkage signal at 9q22-31, we fine mapped this region in an independent collection of colon cancer families. We used a custom array of single-nucleotide polymorphisms (SNP) densely spaced across the candidate region, performing both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. Through this approach, we isolated the association effect to a five-SNP haplotype centered at 98.15 Mb on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to GALNT12, also recently shown to be altered in colon tumors. We used a predictive modeling algorithm to show the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (odds ratio, 3.68), and the accuracy of our prediction model (∼60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q. Cancer Res; 70(13); 5409–18. ©2010 AACR.