Heterogeneity of tibial plateau cartilage in response to a physiological compressive strain rate

Knowledge of the extent to which tibial plateau cartilage displays non‐uniform mechanical topography under physiologically relevant loading conditions is critical to evaluating the role of biomechanics in knee osteoarthritis. Cartilage explants from 21 tibial plateau sites of eight non‐osteoarthritic female cadaveric knees (age: 41–54; BMI: 14–20) were tested in unconfined compression at 100% strain/s. The elastic tangent modulus at 10% strain (E_10%) was calculated for each site and averaged over four geographic regions: not covered by meniscus (I); covered by meniscus—anterior (II); covered by meniscus—exterior (III); and covered by meniscus—posterior (IV). A repeated‐measures mixed model analysis of variance was used to test for effects of plateau, region, and their interaction on E_10%. Effect sizes were calculated for each region pair. E_10% was significantly different (p < 0.05) for all regional comparisons, except I–II and III–IV. The regional pattern of variation was consistent across individuals. Moderate to strong effect sizes were evident for regional comparisons other than I–II on the lateral side and III–IV on both sides. Healthy tibial cartilage exhibits significant mechanical heterogeneity that manifests in a common regional pattern across individuals. These findings provide a foundation for evaluating the biomechanical mechanisms of knee osteoarthritis. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 370–375, 2013     

The role of oxygen as a regulator of stem cell fate during fracture repair in TSP2‐null mice

It is often difficult to decouple the relative importance of different factors in regulating MSC differentiation. Genetically modified mice provide model systems whereby some variables can be manipulated while others are kept constant. Fracture repair in thrombospondin‐2 (TSP2)‐null mice is characterized by reduced endochondral ossification and enhanced intramembranous bone formation. The proposed mechanism for this shift in MSC fate is that increased vascular density and hence oxygen availability in TSP2‐null mice regulates differentiation. However, TSP2 is multifunctional and regulates other aspects of the regenerative cascade, such as MSC proliferation. The objective of this study is to use a previously developed computational model of tissue differentiation, in which substrate stiffness and oxygen tension regulate stem cell differentiation, to simulate potential mechanisms which may drive alterations in MSC fate in TSP2‐null mice. Four models (increased cell proliferation, increased numbers of MSCs in the marrow decreased cellular oxygen consumption, and an initially stiffer callus) were not predictive of experimental observations in TSP2‐null mice. In contrast, increasing the rate of angiogenic progression led to a prediction of greater intramembranous ossification, diminished endochondral ossification, and a reduced region of hypoxia in the fracture callus similar to that quantified experimentally by the immunohistochemical detection of pimonidazole adducts that develop with hypoxia. This study therefore provides further support for the hypothesis that oxygen availability during early fracture healing is a key regulator of MSC bipotential differentiation, and furthermore, it highlights the advantages of integrating computational models with genetically modified mouse studies for further elucidating mechanisms regulating stem cell fate. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1585–1596, 2013.     

Inhibition of Intra-Abdominal Adhesions: A Comparison of Hemaseel APR and Cryoprecipitate Fibrin Glue

Our previous studies demonstrated fibrin glue (FG) prepared from cryoprecipitate (cryo) inhibits intra-abdominal adhesions in rats. A new FG, Hemaseel APR, is Food and Drug Administration (FDA) approved for hemostasis during cardiac surgery and splenic trauma. This study was undertaken to determine if Hemaseel FG prevents intra-abdominal adhesions, and to compare it to cryo FG. Forty-five rats underwent laparotomy. Bilateral peritoneal-muscular defects were created. Polypropylene mesh was sewn into each defect with a running silk suture. The bowel was abraded with gauze. The rats were then randomized to mesh covered with Hemaseel FG, cryo FG, or control. On postoperative day 7, the severity of adhesions were graded by percentage of mesh covered by adhesion (0-100%) and degree of adhesion (0-3). The mean percentage of mesh covered by adhesion was 9% for Hemaseel FG, 43% for cryo FG (p = .005), and 65% for the controls (p &lt; .0001). The mean density adhesion score was 0.5 for Hemaseel FG, 1.2 for cryo FG (p = .04), and 2.1 for the controls (p &lt; .0001). In the Hemaseel FG group, 77% of patches had no adhesions, compared with 37% in the cryo FG group (p = .004) and 13% in the controls (p &lt; .0001). Thus, Hemaseel FG significantly decreases intra-abdominal adhesions, and is more effective than cryo FG.     

Associations between fibroblast growth factor 23 and cardiac characteristics in pediatric heart failure

Background

In adults with heart failure, elevated levels of fibroblast growth factor 23 (FGF23) are associated with mortality. Data on FGF23 levels in pediatric heart failure are lacking.

Patients and methods

We conducted a cross-sectional study of 17 healthy children (mean age 13 years) and 20 pediatric patients with heart failure (mean age 12 years) who underwent echocardiography and for whom the following measurements were taken: plasma FGF23 and parathyroid hormone (PTH) and serum phosphate, creatinine and N-terminal prohormone brain natriuretic peptide (NT-proBNP). Symptom severity was assessed with the New York Heart Association and the Ross classification systems.

Results

Of the 20 patients, 11 had dilated cardiomyopathy, four had congenital heart disease, three had hypertrophic cardiomyopathy, one had a failing heart transplant and one had pulmonary hypertension. Mean phosphate levels in these patients were within the reported reference range for healthy children. Median PTH levels were in the normal range in patients and controls. The median FGF23 level was higher in patients versus controls (110.9 vs. 66.4 RU/ml; P?=?0.03) and higher in patients on diuretics versus other patients (222.4 vs. 82.1 RU/ml; P?=?0.01). Levels of FGF23 and NT-proBNP were directly correlated (r?=?0.47, P?=?0.04), and patients with greater physical functional impairment had higher FGF23 levels (142.5 in those with moderate-severe limitation vs. 92.8 RU/ml in those with no limitation; P?=?0.05). Among patients with dilated cardiomyopathy, higher FGF23 levels were associated with a greater left ventricular end-diastolic diameter (r?=?0.63, P?=?0.04).

Conclusion

FGF23 levels are elevated in children with heart failure and are associated with diuretic use, severity of heart failure and left ventricular dilation.     

Joint hypermobility, obstetrical outcomes, and pelvic floor disorders

Introduction and hypothesis

Benign joint hypermobility syndrome may be a risk factor for pelvic floor disorders. It is unknown whether hypermobility impacts the progress of childbirth, a known risk factor for pelvic floor disorders. Our objective was to investigate the association between joint hypermobility syndrome, obstetrical outcomes, and pelvic floor disorders. Our hypotheses were: (1) women with joint hypermobility are less likely to experience operative delivery and prolonged second-stage labor; and (2) pelvic floor disorders are associated with benign hypermobility syndrome, controlling for obstetrical history.

Methods

Joint hypermobility was measured in 587 parous women (participants in a longitudinal cohort study of pelvic floor disorders after childbirth). Their obstetrical histories were obtained from review of hospital records. Pelvic floor disorders were assessed using validated questionnaires and a structured examination for prolapse. Joint hypermobility and pelvic floor disorders were evaluated at enrollment (5–10 years after first delivery). We compared obstetrical outcomes and pelvic floor disorders between women with and without joint hypermobility, defined as a Beighton score ≥4.

Results

Hypermobility was diagnosed in 46 women (7.8 %) and was associated with decreased odds of cesarean after complete cervical dilation or operative vaginal delivery [odds ratio (OR)?=?0.51; 95 % confidence interval (CI):0.27–0.95]. Anal sphincter laceration was unlikely to occur in women with hypermobility (OR?=?0.19; 95 % CI 0.04–0.80). However, hypermobility was not associated with any pelvic floor disorder considered.

Conclusions

Benign joint hypermobility syndrome may facilitate spontaneous vaginal birth but does not appear to be a risk factor for pelvic floor disorders in the first decade after childbirth.