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

Total knee arthroplasty: the future.

Few areas in orthopaedics have evolved so dramatically over the past few decades as our knowledge of knee physiology, knee kinematics, and knee replacement surgery. This article addresses major breakthroughs in knee replacement surgery, the thought process behind these concepts, and their impact on clinical practice. It focuses on compartmental arthroplasty, use of minimally invasive surgery, advances in biomaterials, and biological solutions for treating arthritis. Compartmental knee replacements are gaining popularity, especially for medial compartment arthritis. Minimally invasive surgery (i.e., quadriceps sparing arthroplasty) has become very popular in the last few years and is being used routinely for unicompartmental knee replacement and increasingly used for total knee replacement. Computer-assisted surgery has the ability to help the surgeon place the components in the desired position, thereby avoiding component malpositioning, which can cause pain, instability, limited range of movement, excessive polyethylene wear, and subsequent implant loosening. Recent advances in the metallurgy have led to the introduction of tantalum trabecular metal which offers several advantages over other current conventional materials used for implants. Expanding knowledge regarding cartilage biochemistry and the pathogenesis of osteoarthritis has focused the research on slowing the progression of osteoarthritis and promoting cartilage matrix synthesis. Perichondrial transplantation as well as periosteal transplantation have been tried by a few investigators but they have limited and temporary success. Autologous chondrocyte implantation is another technique that is gaining popularity. The chondrocytes harvested from the patient are cultured and reimplanted after 3-4 weeks of culturing. In the future, we are likely to see advances in diagnosis as well as management of osteoarthritis. The treatment modalities will probably evolve at the cellular level and it will not be long before a patient-specific medication can be given to a asymptomatic patient in order to prevent development of osteoarthritis. Patients with end-stage osteoarthritis will be offered a combination of treatments (e.g., partial replacement of one compartment or localized cartilage repair if there is localized cartilage defect in the other compartment)

Evidence based management of intracapsular neck of femur fractures

Neck of femur fractures are occurring at an increased incidence. Functionally independent patients without cognitive impairment can expect reasonable life expectancy. This indicates the need for a durable surgical option that optimises the chance to return to pre-injury functional status, with minimal risk of complications and reoperation. Most fractures are displaced. Surgical options include internal fixation, hemiarthroplasty or total hip arthroplasty (THA). Evidence is conclusive that arthroplasty options outperform internal fixation in terms of function, quality of life and reoperation rates. In anyone other than young patients where head preserving surgery is required, arthroplasty is the standard of care. Hemiarthroplasty is the heavily favoured arthroplasty option for surgeons. However, in patients other than the extreme elderly, medically infirm, neurologically impaired, or with little or no ambulatory capacity, the evidence to support hemiarthroplasty is lacking. In functionally independent patients without cognitive impairment, THA should be considered the gold standard, producing better functional and quality of life outcomes, lower reoperation rates and better cost effectiveness, with no difference in complications or mortality. An increased risk of dislocation does exist. This may be reduced with modern surgical technique and implant options. Low amounts of research have been afforded to undisplaced fractures. For this fracture type, surgery is the standard of care. Despite a higher risk of reoperation, internal fixation is the preferred option for all age groups. Further study is required to identify the difference between internal fixation and THA, in particular, for unstable fracture patterns in elderly patients

FIN and osteotomies

10.1007/978-3-642-03031-4_24Flexible Intramedullary Nailing in Children: The Nancy University Manual301-30

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

Walking speed in children and young adults with neuromuscular disease : comparison between two assessment methods

Summary: Self-selected walking speed is being increasingly used as a primary outcome measure in the management of neuromuscular disease. It would be useful if the speed recorded in the gait laboratory represented the child’s walking speed in the community. This study investigated the difference in self selected walking speeds between a 10-meter walk, as measured during instrumented gait analysis, and a 10-minute walk. The authors found that self-selected walking speed during the 10- minute walk was slower than the self-selected walking speed recorded during the 10-meter walk. The former may be more representative of walking speed in the community setting. Walking speed measured during walks of 10 minutes or more should become an integral part of gait laboratory evaluation