Mesenchymal stromal cells and the repair of cartilage tissue

Articular cartilage has a limited intrinsic repair capacity, and thus defects are more likely to further degrade rather than undergo spontaneous self-repair. Whilst a number of surgical techniques have been developed to repair cartilage defects, their efficacy is generally poor and total joint replacement remains the gold standard, albeit last resort, treatment option. Cell-based therapies hold the greatest promise, as they appear uniquely capable of generating de novo cartilage tissue. Two approved therapies (ACI and MACI) are based on the premise that the transplantation of ex vivo expanded autologous chondrocyte populations, harvested from a non-load bearing region of the same joint, could be utilized to effectively regenerate cartilage tissue in the primary defect site. These therapeutic strategies are partially limited by our inability to harvest and expand adequate numbers of autologous chondrocytes that retain the appropriate phenotype. By contrast, the harvest and expansion of large numbers of mesenchymal stem/stromal cells (MSC) derived from tissues such as bone marrow and adipose is comparatively straightforward and has become routine in laboratories worldwide. Additionally, our understanding of the biochemical and biophysical signals required to drive the chondrogenic differentiation of MSC is rapidly increasing. It is conceivable that in the near future MSC expansion and differentiation technologies will offer a means to generate sufficient cell numbers, of an appropriate phenotype, for use in cartilage defect repair. In this chapter we review the relative potential of MSC and their likely contribution to cartilage regeneration.

Noise levels in a General Surgical Ward : a descriptive study

Aims and objectives.  This study was undertaken to measure and analyse levels of acoustic noise in a General Surgical Ward. Method.  Measurements were undertaken using the Norsonic 116 sound level meter (SLM) recording noise levels in the internationally agreed ‘A’ weighted scale. Noise level data and observational data as to the number of staff present were obtained and recorded at 5-min intervals over three consecutive days. Results.  Results of noise level analysis indicated that mean noise level within this clinical area was 42.28 dB with acute spikes reaching 70 dB(A). The lowest noise level attained was that of 36 dB(A) during the period midnight to 7 a.m. Non-parametric testing, using Spearman's Rho (two-tailed), found a positive relationship between the number of staff present and the level of noise recorded, indicating that the presence of hospital personnel strongly influences the level of noise within this area. Relevance to clinical practice.  Whilst the results of this may seem self-evident in many respects the problems of excessive noise production and the exposure to it for patients, hospital personnel and relatives alike continues unabated. What must be of concern is the psychophysiological effects excessive noise exposure has on individuals, for example, decreased wound healing, sleep deprivation and cardiovascular stimulation.

Prostate radiotherapy treatment plan quality : effects of hip prostheses

Introduction This study aimed to examine the geometric and dosimetric results when radiotherapy treatment plans are designed for prostate cancer patients with hip prostheses. Methods Ten EBRT treatment plans for localised prostate cancer, in the presence of hip prostheses, were analysed and compared with a reference set of 196 treatment plans for localised prostate cancer in patients without prostheses. Crowe et al.’s TADA code [1] was used to extract treatment plan parameters and evaluate doses to target volumes and critical structures against recommended goals [2] and constraints [3, 4]. Results The need to avoid transmitting the radiation beam through the hip prostheses limited the range of gantry angles available for use in both the rotational (VMAT) and the non-rotational (3DCRT and IMRT) radiotherapy treatments. This geometric limitation (exemplified in the VMAT data shown in Fig. 1) reduced the overall quality of the treatment plans for patients with prostheses compared to the reference plans. All plans with prostheses failed the PTV dose homogeneity requirement [2], whereas only 4 % of the plans without prostheses failed this test. Several treatment plans for patients with hip prostheses also failed the QUANTEC requirements that less than 50 % of the rectum receive 50 Gy and less than 35 % of the rectum receive 60 Gy to keep the grade 3 toxicity rate below 10 % [3], or the Hansen and Roach requirement that less than 25 % of the bladder receive 75 Gy [4]. Discussion and conclusions The results of this study exemplify the difficulty of designing prostate radiotherapy treatment plans, where beams provide adequate doses to targeted tissues while avoiding nearby organs at risk, when the presence of hip prostheses limits the available treatment geometries. This work provides qualitative evidence of the compromised dose distributions that can result, in such cases.

CTCombine : rotating and combining CT data with an accurate detector model to simulate radiotherapy portal imaging at non-zero beam angles

Established Monte Carlo user codes BEAMnrc and DOSXYZnrc permit the accurate and straightforward simulation of radiotherapy experiments and treatments delivered from multiple beam angles. However, when an electronic portal imaging detector (EPID) is included in these simulations, treatment delivery from non-zero beam angles becomes problematic. This study introduces CTCombine, a purpose-built code for rotating selected CT data volumes, converting CT numbers to mass densities, combining the results with model EPIDs and writing output in a form which can easily be read and used by the dose calculation code DOSXYZnrc...

Polysubstance use in cannabis users referred for treatment: drug use profiles, psychiatric comorbidity and cannabis-related beliefs

Background: Population-based surveys demonstrate cannabis users are more likely to use both illicit and licit substances, compared with non-cannabis users. Few studies have examined the substance use profiles of cannabis users referred for treatment. Co-existing mental health symptoms and underlying cannabis-related beliefs associated with these profiles remains unexplored. Methods: Comprehensive drug use and dependence severity (Severity of Dependence Scale-Cannabis) data were collected on a sample of 826 cannabis users referred for treatment. Patients completed the General Health Questionnaire, Cannabis Expectancy Questionnaire, Cannabis Refusal Self-Efficacy Questionnaire, and Positive Symptoms and Manic-Excitement subscales of the Brief Psychiatric Rating Scale. Latent class analysis was performed on last month use of drugs to identify patterns of multiple drug use. Mental health comorbidity and cannabis beliefs were examined by identified drug use pattern. Results: A three-class solution provided the best fit to the data: (1) cannabis and tobacco users (n = 176), (2) cannabis, tobacco, and alcohol users (n = 498), and (3) wide-ranging sub- stance users (n = 132). Wide-ranging substance users (3) reported higher levels of cannabis dependence severity, negative cannabis expectancies, lower opportunistic, and emotional relief self-efficacy, higher levels of depression and anxiety and higher manic-excitement and positive psychotic symptoms. Conclusion: In a sample of cannabis users referred for treatment, wide-ranging substance use was associated with elevated risk on measures of cannabis dependence, co-morbid psychopathology, and dysfunctional cannabis cognitions. These findings have implications for cognitive-behavioral assessment and treatment.

A biomechanical analysis of growing rods used in the management of early onset scoliosis

INTRODUCTION Managing spinal deformities in young children is challenging, particularly early onset scoliosis (EOS). Surgical intervention is often required if EOS has been unresponsive to conservative treatment particularly with rapidly progressive curves. An emerging treatment option for EOS is fusionless scoliosis surgery. Similar to bracing, this surgical option potentially harnesses growth, motion and function of the spine along with correcting spinal deformity. Dual growing rods are one such fusionless treatment, which aims to modulate growth of the vertebrae. The aim of this study was to ascertain the extent to which semiconstrained growing rods (Medtronic, Sofamor, Danek, Memphis, TN) with a telescopic sleeve component, reduce rotational constraint on the spine compared with standard "constrained / rigid" rods and hence potentially provide a more physiological mechanical environment for the growing spine. METHODS Six 40-60kg English Large White porcine spines served as a model for the paediatric human spine. Each spine was dissected into a 7 level thoracolumbar multi-segment unit (MSU), removing all non-ligamentous soft tissues and leaving 3cm of ribs either side. Pure nondestructive axial rotation moments of ±4Nm at a constant rotation rate of 8deg.s-1 were applied to the mounted MSU spines using a biaxial Instron testing machine. Displacement of each vertebral level was captured using a 3D motion tracking system (Optotrak 3020, Northern Digital Inc, Waterloo, ON). Each spine was tested in an un-instrumented state first and then with appropriately sized semi-constrained growing rods and rigid rods in alternating sequence. The rods were secured by multi-axial pedicle screws (Medtronic CD Horizon) at levels 2 and 6 of the construct. The range of motion (ROM), neutral zone (NZ) size and stiffness (Nm.deg-1) were calculated from the Instron load-displacement data and intervertebral ROM was calculated through a MATLAB algorithm from Optotrak data. RESULTS Irrespective of the order of testing, rigid rods significantly reduced the total ROM compared with semi-constrained rods (p<0.05) with in a significantly stiffer spine for both left and right axial rotation (p<0.05). Analysing the intervertebral motion within the instrumented levels 2-6, rigid rods showed reduced ROM compared with semi-constrained growing rods and compared with un-instrumented motion segments. CONCLUSION Semi-constrained growing rods maintain similar stiffness in axial rotation to un-instrumented spines, while dual rigid rods significantly reduce axial rotation. Clinically the effect of semi-constrained growing rods as observed in this study is that they would be expected to allow growth via the telescopic rod components while maintaining the axial flexibility of the spine, which may reduce occurrence of the crankshaft phenomenon.

Irradiation, cisplatin, and 5-azacytidine upregulate cytomegalovirus promoter in tumors and muscles: Implementation of non-invasive fluorescence imaging

Purpose: The cytomegalovirus (CMV) promoter is one of the most commonly used promoters for expression of transgenes in mammalian cells. The aim of our study was to evaluate the role of methylation and upregulation of the CMV promoter by irradiation and the chemotherapeutic agent cisplatin in vivo using non-invasive fluorescence in vivo imaging. Procedures: Murine fibrosarcoma LPB and mammary carcinoma TS/A cells were stably transfected with plasmids encoding CMV and p21 promoter-driven green fluorescent protein (GFP) gene. Solid TS/A tumors were induced by subcutaneous injection of fluorescent tumor cells, while leg muscles were transiently transfected with plasmid encoding GFP under the control of the CMV promoter. Cells, tumors, and legs were treated either by DNA methylation inhibitor 5-azacytidine, irradiation, or cisplatin. GFP expression was determined using a fluorescence microplate reader in vitro and by non-invasive fluorescence imaging in vivo. Results: Treatment of cells, tumors, and legs with 5-azacytidine (re)activated the CMV promoter. Furthermore, treatment with irradiation or cisplatin resulted in significant upregulation of GFP expression both in vitro and in vivo. Conclusions: Observed alterations in the activity of the CMV promoter limit the usefulness of this widely used promoter as a constitutive promoter. On the other hand, inducibility of CMV promoters can be beneficially used in gene therapy when combined with standard cancer treatment, such as radiotherapy and chemotherapy. © 2010 The Author(s).

Characteristics of epoxy resin/SiO2 nanocomposite insulation : effects of plasma surface treatment on the nanoparticles

The present study compares the effects of two different material processing techniques on modifying hydrophilic SiO2 nanoparticles. In one method, the nanoparticles undergo plasma treatment by using a custom-developed atmospheric-pressure non-equilibrium plasma reactor. With the other method, they undergo chemical treatment which grafts silane groups onto their surface and turns them into hydrophobic. The treated nanoparticles are then used to synthesize epoxy resin-based nanocomposites for electrical insulation applications. Their characteristics are investigated and compared with the pure epoxy resin and nanocomposite fabricated with unmodified nanofillers counterparts. The dispersion features of the nanoparticles in the epoxy resin matrix are examined through scanning electron microscopy (SEM) images. All samples show evidence that the agglomerations are smaller than 30 nm in their diameters. This indicates good dispersion uniformity. The Weibull plot of breakdown strength and the recorded partial discharge (PD) events of the epoxy resin/plasma-treated hydrophilic SiO2 nanocomposite (ER/PTI) suggest that the plasma-treated specimen yields higher breakdown strength and lower PD magnitude as compared to the untreated ones. In contrast, surprisingly, lower breakdown strength is found for the nanocomposite made by the chemically treated hydrophobic particles, whereas the PD magnitude and PD numbers remain at a similar level as the plasma-treated ones.

The cost-effectiveness of total laparoscopic hysterectomy compared to total abdominal hysterectomy for the treatment of early stage endometrial cancer

Objective To summarise how costs and health benefits will change with the adoption of total laparoscopic hysterectomy compared to total abdominal hysterectomy for the treatment of early stage endometrial cancer. Design Cost-effectiveness modelling using the information from a randomised controlled trial. Participants Two hypothetical modelled cohorts of 1000 individuals undergoing total laparoscopic hysterectomy and total abdominal hysterectomy. Outcome measures Surgery costs; hospital bed days used; total healthcare costs; quality-adjusted life years; and net monetary benefits. Results For 1000 individuals receiving total laparoscopic hysterectomy surgery, the costs were $509 575 higher, 3548 hospital fewer bed days were used and total health services costs were reduced by $3 746 221. There were 39.13 more quality-adjusted life years for a 5 year period following surgery. Conclusions The adoption of total laparoscopic hysterectomy is almost certainly a good decision for health services policy makers. There is 100% probability that it will be cost saving to health services, a 86.8% probability that it will increase health benefits and a 99.5% chance that it returns net monetary benefits greater than zero.

A biomechanical analysis of growing rods used in the management of early onset scoliosis

INTRODUCTION Managing spinal deformities in young children is challenging, particularly early-onset scoliosis (EOS). Any progressive spinal deformity particularly in early life presents significant health risks for the child and a challenge for the treating surgeon. Surgical intervention is often required if EOS has been unresponsive to conservative treatment particularly with rapidly progressive curves. An emerging treatment option particularly for EOS is fusionless scoliosis surgery. Similar to bracing this surgical option potentially harnesses growth, motion and function of the spine along with correcting spinal deformity. Dual growing rods is one such fusionless treatment, which aims to modulate growth of the vertebrae. The aim of this study was to ascertain the extent to which semi-constrained growing rods (Medtronic, Memphis, TN) with a telescopic sleeve component, reduce rotational constraint on the spine compared with standard rigid rods and hence potentially provide a more physiological mechanical environment for the growing spine. METHODS Six 40-60kg English Large White porcine spines served as a model for the paediatric human spine. Each spine was dissected into 7 level thoracolumbar multi-segment unit (MSU) spines, removing all non-ligamentous soft tissues. Appropriately sized semi-constrained growing rods and rigid rods were secured by multi-axial screws (Medtronic) prior to testing in alternating sequences for each spine. Pure nondestructive moments of +/4Nm at a constant rotation rate of 8deg/s was applied to the mounted MSU spines. Displacement of each level was captured using an Optotrak (Northern Digital Inc, Waterloo, ON). The range of motion (ROM), neutral zone (NZ) size and stiffness (Nm/deg) were calculated from the Instron load-displacement data and intervertebral ROM was calculated through a MATLAB algorithm from Optotrak data. RESULTS Irrespective of sequence order rigid rods significantly reduced the total ROM (deg) than compared to semi-constrained rods (p<0.05) and resulted in a significantly stiffer (Nm/deg) spine for both left and right axial rotation testing (p<0.05). Analysing the intervertebral motion within the instrumented levels, rigid rods showed reduced ROM (Deg) than compared to semi-constrained growing rods and the un-instrumented (UN-IN) test sequences. CONCLUSION The semi-constrained growing rods maintained rotation similar to UN-IN spines while the rigid rods showed significantly reduced axial rotation across all instrumented levels. Clinically the effect of semi-constrained growing rods evaluated in this study is that they will allow growth via the telescopic rod components while maintaining the axial rotation ability of the spine, which may also reduce the occurrence of the crankshaft phenomenon.

A pilot study to assess the appropriateness of prescribing from a collaborative pharmacist prescribing study in a surgical pre admission clinic

Background Current evidence to support non-medical prescribing is predominantly qualitative, with little evaluation of appropriateness. This study aims to evaluate the appropriateness of prescribing, and significance of omissions, from a doctor pharmacist collaborative prescribing model in an elective surgery pre admission clinic (PAC). Method A modified version of the Medication Appropriate Index (MAI) was developed, piloted and subsequently used by an expert panel, comprised of a surgeon, anaesthetist, clinical pharmacologist, pharmacist, resident medical officer (RMO) and clinical nurse. The tool was used to rate the appropriateness of prescribing of medications, and the significance of omissions in a 5% sample (N=19) of the total cohort from a randomised, controlled two arm trial of doctor-pharmacist collaborative prescribing. Results When reviewer assessments were combined, 32 out of 294 (10.9%) medications assessed for appropriateness in the control arm were classed as inappropriate, compared to 13 of 266 (4.9%) in the intervention arm. Out of 89 regular medications in the control arm, 25 (28%) were omitted from the medication charts, compared to 1 out of 55 (2%) in the intervention arm (p<0.001, fishers exact) On average, 52% of omissions in the control arm were judged to have potential for patient harm or ward inconvenience. Conclusion For the appropriateness of prescribing, overall results were similar between arms, as judged by individual panel members. Medication charts in the control arm contained significantly more omissions than in the intervention arm, a number of which were rated by the panel members as having the potential for patient harm or ward inconvenience.

In-hospital mortality rates after a cemented femoral component for displaced neck of femur fractures

Aim This prospective cohort study investigated whether the use of preoperative anticoagulants is an independent risk factor for the outcomes of surgical treatment of patients with a neck of femur fracture. Methods Data was obtained from a prospectively collected database. All patients admitted for a neck of femur fracture between Nov 2010 and Oct 2011 were included. This resulted in three hundred twenty-eight patients with 330 neck of femur fractures. Four groups were defined; patients preoperatively (i) on aspirin (n = 105); (ii) on clopidogrel (n = 28); (iii) on warfarin (n = 30), and; (iv) without any anticoagulation history (n = 167, the control group). The non-warfarin group included the aspirin group, clopidogrel group and the control group. Primary outcome was the in-hospital mortality. Secondary outcomes were the postoperative complications, return to theatre and length of stay. Results Thirteen in-hospital deaths were identified, 4 deaths in the aspirin group, 1 death in the clopidogrel group, 2 deaths in the warfarin group and 6 deaths in the control group. No significant difference in the mortality rates was found between the different groups. Also in the secondary outcomes, no significant difference was found between the four groups. A trend to a higher wound complication rate for the warfarin group was detected. Conclusion The use of clopidrogel or aspirin pre operatively is not an influence on short term patient outcome for patients with a neck of femur fracture. Surgical procedures should not be delayed to reverse their influence.

The effect of hip muscle strengthening on pain and disability for individuals with non-specific low back pain : a randomized controlled trial

Introduction Clinical guidelines for the treatment of chronic low back pain suggest the use of supervised exercise. Motor control (MC) based exercise is widely used within clinical practice but its efficacy is equivalent to general exercise therapy. MC exercise targets the trunk musculature. Considering the mechanical links between the hip, pelvis, and lumbar spine, surprisingly little focus has been on investigating the contribution of the hip musculature to lumbopelvic support. The purpose of this study is to compare the efficacy of two exercise programs for the treatment of non-specific low back pain (NSLBP). Methods Eighty individuals aged 18-65 years of age were randomized into two groups to participate in this trial. The primary outcome measures included self-reported pain intensity (0-100mm VAS) and percent disability (Oswestry Disability Index V2). Bilateral measures of hip strength (N/kg) and two dimensional frontal plane mechanics (º) were the secondary outcomes. Outcomes were measured at baseline and following a six-week home based exercise program including weekly sessions of real-time ultrasound imaging. Results Within group comparisons revealed clinically meaningful reductions in pain for both groups. The MC exercise only (N= 40, xˉ =-20.9mm, 95%CI -25.7, -16.1) and the combined MC and hip exercise (N= 40, xˉ = -24.9mm, 95%CI -30.8, -19.0). There was no statistical difference in the change of pain (xˉ =-4.0mm, t= -1.07, p=0.29, 95%CI -11.5, 3.5) or disability (xˉ =-0.3%, t=-0.19, p=0.85, 95%CI -11.5, 3.5) between groups. Conclusion Both exercise programs had similar and positive effects on NSLBP which support the use of the home based exercise programs with weekly supervised visits. However, the addition of specific hip strengthening exercises to a MC based exercise program did not result in significantly greater reductions in pain or disability. Trial Registration NCTO1567566 Funding: Worker’s Compensation Board Alberta Research Grant.

A comparison of treatment options for management of end stage kidney disease in elderly patients : a systematic review

Background Chronic kidney disease is a global public health problem of increasing prevalence. There are five stages of kidney disease, with Stage 5 indicating end stage kidney disease (ESKD) requiring dialysis or death will eventually occur. Over the last two decades there have been increasing numbers of people commencing dialysis. A majority of this increase has occurred in the population of people who are 65 years and over. With the older population it is difficult to determine at times whether dialysis will provide any benefit over non-dialysis management. The poor prognosis for the population over 65 years raises issues around management of ESKD in this population. It is therefore important to review any research that has been undertaken in this area which compares outcomes of the older ESKD population who have commenced dialysis with those who have received non-dialysis management. Objective The primary objective was to assess the effect of dialysis compared with non-dialysis management for the population of 65 years and over with ESKD. Inclusion criteria Types of participants This review considered studies that included participants who were 65 years and older. These participants needed to have been diagnosed with ESKD for greater than three months and also be either receiving renal replacement therapy (RRT) (hemodialysis [HD] or peritoneal dialysis [PD]) or non-dialysis management. The settings for the studies included the home, self-care centre, satellite centre, hospital, hospice or nursing home. Types of intervention(s)/phenomena of interest This review considered studies where the intervention was RRT (HD or PD) for the participants with ESKD. There was no restriction on frequency of RRT or length of time the participant received RRT. The comparator was participants who were not undergoing RRT. Types of studies This review considered both experimental and epidemiological study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies. This review also considered descriptive epidemiological study designs including case series, individual case reports and descriptive cross sectional studies for inclusion. This review included any of the following primary and secondary outcome measures: •Primary outcome – survival measures •Secondary outcomes – functional performance score (e.g. Karnofsky Performance score) •Symptoms and severity of end stage kidney disease •Hospital admissions •Health related quality of life (e.g. KDQOL, SF36 and HRQOL) •Comorbidities (e.g. Charlson Comorbidity index).