Glucocorticoid receptor alters isovolumetric contraction and restrains cardiac fibrosis

Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention is focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with that of littermate controls. Doppler measurements of blood flow across the mitral valve showed an elongated isovolumetric contraction time in surviving adult SMGRKO mice, indicating impairment of the initial left ventricular contractile phase. Although heart weight was elevated in both genders, only male SMGRKO mice showed evidence of pathological cardiomyocyte hypertrophy, associated with increased myosin heavy chain-β expression. Left ventricular fibrosis, evident in both genders, was associated with elevated levels of mRNA encoding MR as well as proteins involved in cardiac remodelling and fibrosis. However, MR antagonism with spironolactone from birth only modestly attenuated the increase in pro-fibrotic gene expression in SMGRKO mice, suggesting that elevated MR signalling is not the primary driver of cardiac fibrosis in SMGRKO mice, and cardiac fibrosis can be dissociated from MR activation. Thus, GR contributes to systolic function and restrains normal cardiac growth, the latter through gender-specific mechanisms. Our findings suggest the GR:MR balance is critical in corticosteroid signalling in specific cardiac cell types

Development of spasticity with age in a total population of children with cerebral palsy

<p>Abstract</p> <p>Background</p> <p>The development of spasticity with age in children with cerebral palsy (CP) has, to our knowledge, not been studied before. In 1994, a register and a health care program for children with CP in southern Sweden were initiated. In the programme the child's muscle tone according to the modified Ashworth scale is measured twice a year until six years of age, then once a year. We have used this data to analyse the development of spasticity with age in a total population of children with cerebral palsy.</p> <p>Methods</p> <p>All measurements of muscle tone in the gastrocnemius-soleus muscle in all children with CP from 0 to 15 years during the period 1995–2006 were analysed. The CP subtypes were classified according to the Surveillance of Cerebral Palsy in Europe network system. Using these criteria, the study was based on 6218 examinations in 547 children. For the statistical analysis the Ashworth scale was dichotomized. The levels 0–1 were gathered in one category and levels 2–4 in the other. The pattern of development with age was evaluated using piecewise logistic regression in combination with Akaike's An Information Criterion.</p> <p>Results</p> <p>In the total sample the degree of muscle tone increased up to 4 years of age. After 4 years of age the muscle tone decreased each year up to 12 years of age. A similar development was seen when excluding the children operated with selective dorsal rhizotomy, intrathecal baclofen pump or tendo Achilles lengthening. At 4 years of age about 47% of the children had spasticity in their gastro-soleus muscle graded as Ashworth 2–4. After 12 years of age 23% of the children had that level of spasticity. The CP subtypes spastic bilateral and spastic unilateral CP showed the same pattern as the total sample. Children with dyskinetic type of CP showed an increasing muscle tone up to age 6, followed by a decreasing pattern up to age 15.</p> <p>Conclusion</p> <p>In children with CP, the muscle tone as measured with the Ashworth scale increases up to 4 years of age and then decreases up to 12 years of age. The same tendency is seen in all spastic subtypes. The findings may have implications both for clinical judgement and for research studies on spasticity treatment.</p

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Femoral derotation osteotomy in spastic diplegia

We describe the results of a prospective study of 28 children with spastic diplegia and in-toed gait, who had bilateral femoral derotation osteotomies undertaken at either the proximal intertrochanteric or the distal supracondylar level of the femur. Preoperative clinical evaluation and three-dimensional movement analysis determined any additional soft-tissue surgery. Distal osteotomy was faster with significantly lower blood loss than proximal osteotomy. The children in the distal group achieved independent walking earlier than those in the proximal group (6.9 ± 1.3 v 10.7 ± 1.7 weeks; p < 0.001). Transverse plane kinematics demonstrated clinically significant improvements in rotation of the hip and the foot progression angle in both groups. Correction of rotation of the hip was from 17 ± 11° internal to 3 ± 9.5° external in the proximal group and from 9 ± 14° internal to 4 ± 12.4° external in the distal group. Correction of the foot progression angle was from a mean of 10.0 ± 17.3° internal to 13.0 ± 11.8° external in the proximal group (p < 0.001) compared with a mean of 7.0 ± 19.4° internal to 10.0 ± 12.2° external in the distal group (p < 0.001). Femoral derotation osteotomy at both levels gives comparable excellent correction of rotation of the hip and foot progression angles in children with spastic diplegia