Aldose Reductase (AR) Mediates and Perivascular Adipose Tissue (PVAT) Modulates Endothelial Dysfunction of Short-Term High-Fat Diet Feeding in Mice.

Increased adiposity of both visceral and perivascular adipose tissue (PVAT) depots is associated with an increased risk of diabetes and cardiovascular disease (CVD). Under healthy conditions, PVAT modulates vascular tone via the release of PVAT-derived relaxing factors, including adiponectin and leptin. However, when PVAT expands with high-fat diet (HFD) feeding, it appears to contribute to the development of endothelial dysfunction (ED). Yet, the mechanisms by which PVAT alters vascular health are unclear. Aldose reductase (AR) catalyzes glucose reduction in the first step of the polyol pathway and has been long implicated in diabetic complications including neuropathy, retinopathy, nephropathy, and vascular diseases. To better understand the roles of both PVAT and AR in HFD-induced ED, we studied structural and functional changes in aortic PVAT induced by short-term HFD (60% kcal fat) feeding in wild type (WT) and aldose reductase-null (AR-null) mice. Although 4 weeks of HFD feeding significantly increased body fat and PVAT mass in both WT and AR-null mice, HFD feeding induced ED in the aortas of WT mice but not of AR-null mice. Moreover, HFD feeding augmented endothelial-dependent relaxation in aortas with intact PVAT only in WT and not in AR-null mice. These data indicate that AR mediates ED associated with short-term HFD feeding and that ED appears to provoke 'compensatory changes' in PVAT induced by HFD. As these data support that the ED of HFD feeding is AR-dependent, vascular-localized AR remains a potential target of temporally selective intervention.

Use of Shorter Intramedullary Guide for Ipsilateral Total Knee Arthroplasty following Prior Total Hip Arthroplasty.

Alignment after total knee arthroplasty (TKA) plays an important role with respect to patient satisfaction and implant survivorship. In patients undergoing ipsilateral TKA with prior total hip arthroplasty (THA), the femoral intramedullary (IM) guide cannot be fully inserted into the femoral canal because of the prior THA. The purpose of this study was to determine the effect of femoral component alignment using a shorter IM guide during TKA in patients with an ipsilateral THA. We identified 42 patients undergoing ipsilateral TKA with the use of a short IM guide in the setting of a prior THA. A matched cohort group was identified from our total joint registry that included 42 patients who underwent primary TKA. The surgical goal was to achieve 5 degrees of valgus on the femoral side and 0 degree on the tibial side with an overall postoperative tibial-femoral angle of 5 degrees of valgus. Patients were evaluated clinically using Knee Society pain scores (KSSs), function scores, and with radiography. Both the tibial-femoral limb alignment and the femoral component alignment were compared using Student's t-test. There were no significant differences between the two groups with respect to sex, age, body mass index (BMI), pre- and postoperative KSSs. There was a statistically significant difference between the two groups with respect to radiographic tibial-femoral limb alignment, 4.33 degrees of valgus in the short stem THA-TKA group versus 5.4 degrees of valgus in the TKA group (p < 0.04); however, this difference did not correlate to a difference in postoperative outcomes. An adequate tibial-femoral component alignment was achieved in patients undergoing ipsilateral TKA with prior THA using a shortened IM femoral guide.

International knee documentation committee knee survey use after anterior cruciate ligament reconstruction: a 2005-2012 systematic review and world region comparison.

PURPOSE: The purpose of this review was to evaluate International Knee Documentation Committee (IKDC) survey use after anterior cruciate ligament reconstruction compared with other surveys and determine evidence levels and methodologic study quality by world region. METHODS: The Medline database was searched from January 2005 through December 2012. RESULTS: We identified 421 studies and 33 surveys. Europe and Australia had more objective and subjective IKDC form use (χ(2) = 9.6, P = .047). Europe and Asia had more objective IKDC form use (χ(2) = 19.4, P = .001). Asia had more Lysholm knee scale use (χ(2) = 29.9, P < .0001). Europe had more Tegner Activity Level scale (χ(2) = 31.7, P < .0001) and Knee Injury and Osteoarthritis Outcome Score (χ(2) = 20.5, P < .0001) use. North America and Australia had more Cincinnati or Noyes knee rating scale use (χ(2) = 21, P < .0001). Asia and Australia had more studies with greater than 60 subjects (χ(2) = 24.4, P = .018). Europe had more studies with greater than 24 months' follow-up (χ(2) = 18.4, P = .018). Asia had more studies with adequate surgical descriptions (χ(2) = 33.2, P < .0001). North America had more studies with well-described rehabilitation (χ(2) = 18.2, P = .02). Europe had more studies with confirmed recruitment (χ(2) = 12.9, P = .012). Australia and North America had more studies with confirmed independent investigators (χ(2) = 11.1, P = .026). Europe had more studies with greater than 80% recruitment (χ(2) = 16.0, P = .04). Methodologically stronger studies used the objective IKDC survey (P < .0001), the objective and subjective IKDC survey (P = .002), or the Cincinnati or Noyes scale (P = .002). This group also made greater use of the Tegner scale (P = .013). CONCLUSIONS: Objective and subjective IKDC form use is comparable with Lysholm and Tegner scale use. Objective and subjective IKDC form use in combination with the Tegner Activity Level scale is recommended. LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies.

A genome-wide linkage scan identifies multiple quantitative trait loci for HDL-cholesterol levels in families with premature CAD and MI.

Plasma HDL cholesterol levels (HDL-C) are an independent predictor of coronary artery disease (CAD). We have completed a genome-wide linkage scan for HDL-C in a US cohort consisting of 388 multiplex families with premature CAD (GeneQuest). The heritability of HDL-C in GeneQuest was 0.37 with gender and age as covariates (P = 5.1 x 10(-4)). Two major quantitative trait loci (QTL) for log-transformed HDL-C adjusted for age and gender were identified onto chromosomes 7p22 and 15q25 with maximum multipoint logarithm of odds (LOD) scores of 3.76 and 6.69, respectively. Fine mapping decreased the 7p22 LOD score to a nonsignificant level of 3.09 and split the 15q25 QTL into two loci, one minor QTL on 15q22 (LOD = 2.73) that spanned the LIPC gene, and the other at 15q25 (LOD = 5.63). A family-based quantitative transmission disequilibrium test (QTDT) revealed significant association between variant rs1800588 in LIPC and HDL-C in the GeneQuest population (P = 0.0067), which may account for the minor QTL on 15q22. The 15q25 QTL is the most significant locus identified for HDL-C to date, and these results provide a framework for the ultimate identification of the underlying HDL-C variant and gene on chromosomes 15q25, which will provide insights into novel regulatory mechanisms of HDL-C metabolism.