I-cobb - An innovative technique in spinal radiographic measurement

The measurement of Cobb angles on radiographs of patients with spinal deformities is routine practice in spinal clinics. The technique relies on the use and availability of specialist equipment such as a goniometer, cobbometer or protractor. The aim of this study was to validate the use of i-Phone (Apple Inc) combined with Tilt Meter Pro software as compared to a protractor in the measurement of Cobb angles. The i-Phone combined with Tilt Meter Pro software offers a faster alternative to the traditional method of Cobb angle measurement. The use of i-Phone offers a more convenient way of measuring Cobb angles in the outpatient setting. The intra-observer repeatability of the iPhone is equivalent to the protractor in the measurement of Cobb angles.

Falls in Parkinson's disease : kinematic evidence for impaired head and trunk control

Changes in stride characteristics and gait rhythmicity characterize gait in Parkinson's disease and are widely believed to contribute to falls in this population. However, few studies have examined gait in PD patients who fall. This study reports on the complexities of walking in PD patients who reported falling during a 12-month follow-up. Forty-nine patients clinically diagnosed with idiopathic PD and 34 controls had their gait assessed using three-dimensional motion analysis. Of the PD patients, 32 (65%) reported at least one fall during the follow-up compared with 17 (50%) controls. The results showed that PD patients had increased stride timing variability, reduced arm swing and walked with a more stooped posture than controls. Additionally, PD fallers took shorter strides, walked slower, spent more time in double-support, had poorer gait stability ratios and did not project their center of mass as far forward of their base of support when compared with controls. These stride changes were accompanied by a reduced range of angular motion for the hip and knee joints. Relative to walking velocity, PD fallers had increased mediolateral head motion compared with PD nonfallers and controls. Therefore, head motion could exceed “normal” limits, if patients increased their walking speed to match healthy individuals. This could be a limiting factor for improving gait in PD and emphasizes the importance of clinically assessing gait to facilitate the early identification of PD patients with a higher risk of falling.

Corneal confocal microscopy : a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

OBJECTIVE: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. ---------- RESEARCH DESIGN AND METHODS: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). ---------- RESULTS: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74). ---------- CONCLUSIONS: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. Established diabetic neuropathy leads to pain and foot ulceration. Detecting neuropathy early may allow intervention with treatments to slow or reverse this condition (1). Recent studies suggested that small unmyelinated C-fibers are damaged early in diabetic neuropathy (2–4) but can only be detected using invasive procedures such as sural nerve biopsy (4,5) or skin-punch biopsy (6–8). Our studies have shown that corneal confocal microscopy (CCM) can identify early small nerve fiber damage and accurately quantify the severity of diabetic neuropathy (9–11). We have also shown that CCM relates to intraepidermal nerve fiber loss (12) and a reduction in corneal sensitivity (13) and detects early nerve fiber regeneration after pancreas transplantation (14). Recently we have also shown that CCM detects nerve fiber damage in patients with Fabry disease (15) and idiopathic small fiber neuropathy (16) when results of electrophysiology tests and quantitative sensory testing (QST) are normal. In this study we assessed corneal sensitivity and corneal nerve morphology using CCM in diabetic patients stratified for the severity of diabetic neuropathy using neurological evaluation, electrophysiology tests, and QST. This enabled us to compare CCM and corneal esthesiometry with established tests of diabetic neuropathy and define their sensitivity and specificity to detect diabetic patients with early neuropathy and those at risk of foot ulceration.

Pedunculopontine nucleus deep brain stimulation produces sustained improvement in primary progressive freezing of gait

Objective: To assess the efficacy of bilateral pedunculopontine nucleus (PPN) deep brain stimulation (DBS) as a treatment for primary progressive freezing of gait (PPFG). ------ ----- Methods: A patient with PPFG underwent bilateral PPN-DBS and was followed clinically for over 14 months. ------ ----- Results: The PPFG patient exhibited a robust improvement in gait and posture following PPN-DBS. When PPN stimulation was deactivated, postural stability and gait skills declined to pre-DBS levels, and fluoro-2-deoxy-d-glucose positron emission tomography revealed hypoactive cerebellar and brainstem regions, which significantly normalised when PPN stimulation was reactivated. ------ ----- Conclusions: This case demonstrates that the advantages of PPN-DBS may not be limited to addressing freezing of gait (FOG) in idiopathic Parkinson's disease. The PPN may also be an effective DBS target to address other forms of central gait failure.

Interactive image manipulation for surgical planning

The Australian e-Health Research Centre in collaboration with the Queensland University of Technology's Paediatric Spine Research Group is developing software for visualisation and manipulation of large three-dimensional (3D) medical image data sets. The software allows the extraction of anatomical data from individual patients for use in preoperative planning. State-of-the-art computer technology makes it possible to slice through the image dataset at any angle, or manipulate 3D representations of the data instantly. Although the software was initially developed to support planning for scoliosis surgery, it can be applied to any dataset whether obtained from computed tomography, magnetic resonance imaging or any other imaging modality.

Elevated plasma fibronectin levels associated with venous thromboembolism

Elevated plasma fibronectin levels occur in various clinical states including arterial disease. Increasing evidence suggests that atherothrombosis and venous thromboembolism (VTE) share common risk factors. To assess the hypothesis that high plasma fibronectin levels are associated with VTE, we compared plasma fibronectin levels in the Scripps Venous Thrombosis Registry for 113 VTE cases vs. age and sex matched controls. VTE cases had significantly higher mean fibronectin concentration compared to controls (127% vs. 103%, p<0.0001); the difference was greater for idiopathic VTE cases compared to secondary VTE cases (133% vs. 120%, respectively). Using a cut-off of >90% of the control values, the odds ratio (OR) for association of VTE for fibronectin plasma levels above the 90th percentile were 9.37 (95% CI 2.73-32.2; p<0.001) and this OR remained significant after adjustment for sex, age, body mass index (BMI), factor V Leiden and prothrombin nt20210A (OR 7.60, 95% CI 2.14-27.0; p=0.002). In particular, the OR was statistically significant for idiopathic VTE before and after these statistical adjustments. For the total male cohort, the OR was significant before and after statistical adjustments and was not significant for the total female cohort. In summary, our results suggest that elevated plasma fibronectin levels are associated with VTE especially in males, and extend the potential association between biomarkers and risk factors for arterial atherothrombosis and VTE. © 2008 Schattauer GmbH.

Is the iPhone an accurate and useful tool for the monitoring of spinal deformity?

The progression of spinal deformity is traditionally monitored by spinal surgeons using the Cobb method on hardcopy radiographs with a protractor and pencil. The rotation of the spine and ribcage (rib hump) in scoliosis is measured with a simple hand-held inclinometer (Scoliometer). The iPhone and other smart phones have the capability to accurately sense inclination, and can therefore be used to measure Cobb angles and rib hump angulation. The purpose of this study was to quantify the performance of the iPhone compared to a standard protractor for measuring Cobb angles and the Scoliometer for measuring rib humps. The study concluded that the iPhone is a clinically equivalent measuring tool to the traditional protractor and Scoliometer

Polycaprolactone-based scaffold plus rhBMP-2 in a sheep thoracic spine fusion model

We report the application of a novel scaffold design in a sheep thoracic spine model for spine deformity correction. The combination of the calcium-phosphate coated polycaprolactone scaffolds with recombinant human bone morphogenic protein-2 (rhBMP-2) are intended as a future bone graft substitute in ensuring the stability of bony intervertebral fusion. A solid free-form fabrication process based on melt extrusion has been utilized in the manufacturing of these scaffolds. To date there are no studies examining the use of such biodegradable implants in a sheep thoracic spine model. The success of anterior scoliosis surgery in humans depends on achieving a solid bony fusion between adjacent vertebrae after the intervertebral discs have been surgically cleared and the disc spaces filled with graft material. Due to limited availability of autograft, there is much current interest in the development of synthetic scaffolds in combination with growth factors such as recombinant human bone morphogenetic protein (rhBMP-2) to achieve a solid bony fusion following scoliosis surgery.

Effects of surgical joint destabilization on load sharing between ligamentous structures in the thoracic spine : a finite element investigation

Background: In vitro investigations have demonstrated the importance of the ribcage in stabilising the thoracic spine. Surgical alterations of the ribcage may change load-sharing patterns in the thoracic spine. Computer models are used in this study to explore the effect of surgical disruption of the rib-vertebrae connections on ligament load-sharing in the thoracic spine. Methods: A finite element model of a T7-8 motion segment, including the T8 rib, was developed using CT-derived spinal anatomy for the Visible Woman. Both the intact motion segment and the motion segment with four successive stages of destabilization (discectomy and removal of right costovertebral joint, right costotransverse joint and left costovertebral joint) were analysed for a 2000Nmm moment in flexion/extension, lateral bending and axial rotation. Joint rotational moments were compared with existing in vitro data and a detailed investigation of the load sharing between the posterior ligaments carried out. Findings: The simulated motion segment demonstrated acceptable agreement with in vitro data at all stages of destabilization. Under lateral bending and axial rotation, the costovertebral joints were of critical importance in resisting applied moments. In comparison to the intact joint, anterior destabilization increases the total moment contributed by the posterior ligaments. Interpretation: Surgical removal of the costovertebral joints may lead to excessive rotational motion in a spinal joint, increasing the risk of overload and damage to the remaining ligaments. The findings of this study are particularly relevant for surgical procedures involving rib head resection, such as some techniques for scoliosis deformity correction.

Microbial colonisation of human follicular fluid and adverse in vitro fertilisation outcomes

This study, investigating 263 women undergoing trans-vaginal oocyte retrieval for in vitro fertilisation (IVF) found that microorganisms colonising follicular fluid contributed to adverse IVF (pre-implantation) and pregnancy (post-implantation) outcomes including poor quality embryos, failed pregnancy and early pregnancy loss (< 37 weeks gestation). Some microorganisms also showed in vitro growth patterns in liquid media that appeared to be enhanced by the hormonal stimulation protocol used for oocyte retrieval. Elaborated cytokines within follicular fluid were also associated with adverse IVF outcomes. This study is imperative because infertility affects 16% of the human population and the numbers of couples needing assistance continues to increase. Despite significant improvements in the technical aspects of assisted reproductive technologies (ART), the live birth rate has not increased proportionally. Overt genital tract infection has been associated with both infertility and adverse pregnancy outcomes (including miscarriage and preterm birth) as a direct result of the infection or the host response to it. Importantly, once inflammation had become established, medical treatment often failed to prevent these significant adverse outcomes. Current evaluations of fertility focus on the ovary as a site of steroid hormone production and ovulation. However, infertility as a result of subclinical colonisation of the ovary has not been reported. Furthermore, identification of the microorganisms present in follicular fluid and the local cytokine profile may provide clinicians with an early indication of the prognosis for IVF treatment in infertile couples, thus allowing antimicrobial treatment and/or counselling about possible IVF failure. During an IVF cycle, multiple oocytes undergo maturation in vivo in response to hormonal hyperstimulation. Oocytes for in vitro insemination are collected trans-vaginally. The follicular fluid that bathes the maturing oocyte in vivo, usually is discarded as part of the IVF procedure, but provides a unique opportunity to investigate microbial causes of adverse IVF outcomes. Some previous studies have identified follicular fluid markers that predict IVF pregnancy outcomes. However, there have not been any detailed microbiological studies of follicular fluid. For this current study, paired follicular fluid and vaginal secretion samples were collected from women undergoing IVF cycles to determine whether microorganisms in follicular fluid were associated with adverse IVF outcomes. Microorganisms in follicular fluid were regarded as either "colonisers" or "contaminants"; colonisers, if they were unique to the follicular fluid sample, and contaminants if the same microorganisms were detected in the vaginal and follicular fluid samples indicating that the follicular fluid was merely contaminated during the oocyte retrieval process. Quite unexpectedly, by these criteria, we found that follicular fluid from approximately 30% of all subjects was colonised with bacteria. Fertile and infertile women with colonised follicular fluid had decreased embryo transfer rates and decreased pregnancy rates compared to women with contaminated follicular fluids. The observation that follicular fluid was not always sterile, but contained a diverse range of microorganisms, is novel. Many of the microorganisms we detected in follicular fluid are known opportunistic pathogens that have been detected in upper genital tract infections and are associated with adverse pregnancy outcomes. Bacteria were able to survive for at least 28 weeks in vitro, in cultures of follicular fluid. Within 10 days of establishing these in vitro cultures, several species (Lactobacillus spp., Bifidobacterium spp., Propionibacterium spp., Streptococcus spp. and Salmonella entericus) had formed biofilms. Biofilms play a major role in microbial pathogenicity and persistence. The propensity of microbial species to form biofilms in follicular fluid suggests that successful treatment of these infections with antimicrobials may be difficult. Bifidobacterium spp. grew, in liquid media, only if concentrations of oestradiol and progesterone were similar to those achieved in vivo during an IVF cycle. In contrast, the growth of Streptococcus agalactiae and Escherichia coli was inhibited or abolished by the addition of these hormones to culture medium. These data suggest that the likelihood of microorganisms colonising follicular fluid and the species of bacteria involved is influenced by the stage of the menstrual cycle and, in the case of IVF, the nature and dose of steroid hormones administered for the maturation of multiple oocytes in vivo. Our findings indicate that the elevated levels of steroid hormones during an IVF cycle may influence the microbial growth within follicular fluid, suggesting that the treatment itself will impact on the microflora present in the female upper genital tract during pre-conception and early post-conception phases of the cycle. The effect of the host immune response on colonising bacteria and on the outcomes of IVF also was investigated. White blood cells reportedly compose between 5% and 15% of the cell population in follicular fluid. The follicular membrane is semi-permeable and cells are actively recruited as part of the normal menstrual cycle and in response to microorganisms. A previous study investigated follicular fluid cytokines from infertile women and fertile oocyte donors undergoing IVF, and concluded that there were no significant differences in the cytokine concentrations between the two groups. However, other studies have reported differences in the follicular fluid cytokine levels associated with infertile women with endometriosis or polycystic ovary syndrome. In this study, elevated levels of interleukin (IL)-1 á, IL-1 â and vascular endothelial growth factor (VEGF) in vaginal fluid were associated with successful fertilisation, which may be useful marker for successful fertilisation outcomes for women trying to conceive naturally or prior to oocyte retrieval for IVF. Elevated levels of IL-6, IL-12p40, granulocyte colony stimulating factor (GCSF) and interferon-gamma (IFN ã) in follicular fluid were associated with successful embryo transfer. Elevated levels of pro-inflammatory IL-18 and decreased levels of anti-inflammatory IL-10 were identified in follicular fluid from women with idiopathic infertility. Successful fertilisation and implantation is dependent on a controlled pro-inflammatory environment, involving active recruitment of pro-inflammatory mediators to the genital tract as part of the menstrual cycle and early pregnancy. However, ongoing pregnancy requires an enhanced anti-inflammatory environment to ensure that the maternal immune system does not reject the semi-allergenic foetus. The pro-inflammatory skew in the follicular fluid of women with idiopathic infertility, correlates with normal rates of fertilisation, embryo discard and embryo transfer, observed for this cohort, which were similar to the outcomes observed for fertile women. However, their pregnancy rate was reduced compared to fertile women. An altered local immune response in follicular fluid may provide a means of explaining infertility in this cohort, previously defined as 'idiopathic'. This study has found that microorganisms colonising follicular fluid may have contributed to adverse IVF and pregnancy outcomes. Follicular fluid bathes the cumulus oocyte complex during the in vivo maturation process, and microorganisms in the fluid, their metabolic products or the local immune response to these microorganisms may result in damage to the oocytes, degradation of the cumulus or contamination of the IVF culture system. Previous studies that have discounted bacterial contamination of follicular fluid as a cause of adverse IVF outcomes failed to distinguish between bacteria that were introduced into the follicular fluid at the time of trans-vaginal oocyte retrieval and those that colonised the follicular fluid. Those bacteria that had colonised the fluid may have had time to form biofilms and to elicit a local immune response. Failure to draw this distinction has previously prevented consideration of bacterial colonisation of follicular fluid as a cause of adverse IVF outcomes. Several observations arising from this study are of significance to IVF programs. Follicular fluid is not always sterile and colonisation of follicular fluid is a cause of adverse IVF and pregnancy outcomes. Hormonal stimulation associated with IVF may influence whether follicular fluid is colonised and enhance the growth of specific species of bacteria within follicular fluid. Bacteria in follicular fluid may form biofilms and literature has reported that this may influence their susceptibility to antibiotics. Monitoring the levels of selected cytokines within vaginal secretions may inform fertilisation outcomes. This study has identified novel factors contributing to adverse IVF outcomes and that are most likely to affect also natural conception outcomes. Early intervention, possibly using antimicrobial or immunological therapies may reduce the need for ART and improve reproductive health outcomes for all women.

Towards determining soft tissue properties for modelling spine surgery : current progress and challenges

Current complication rates for adolescent scoliosis surgery necessitate the development of better surgical planning tools to improve outcomes. Here we present our approach to developing finite element models of the thoracolumbar spine for deformity surgery simulation, with patient-specific model anatomy based on low-dose pre-operative computed tomography scans. In a first step towards defining patient-specific tissue properties, an initial 'benchmark' set of properties were used to simulate a clinically performed pre-operative spinal flexibility assessment, the fulcrum bending radiograph. Clinical data for ten patients were compared with the simulated results for this assessment and in cases where these data differed by more than 10%, soft tissue properties for the costo-vertebral joint (CVJt) were altered to achieve better agreement. Results from these analyses showed that changing the CVJt stiffness resulted in acceptable agreement between clinical and simulated flexibility in two of the six cases. In light of these results and those of our previous studies in this area, it is suggested that spinal flexibility in the fulcrum bending test is not governed by any single soft tissue structure acting in isolation. More detailed biomechanical characterisation of the fulcrum bending test is required to provide better data for determination of patient-specific soft tissue properties.

Is the iPhone a useful clinical tool to monitor spinal deformity patients?

The progression of spinal deformity is traditionally monitored on hard copy radiographs using the Cobb method with a protractor and pencil. The rotation of the spine and ribcage (rib hump) in scoliosis is measured with a hand-held inclinometer/Scoliometer. The iPhone and other smart phones, can accurately sense inclination, and can therefore be used to measure Cobb angles and rib hump angulation. The purpose of this study was to quantify the performance of the iPhone compared to the standard protractor (Cobb angles) and the Scoliometer (rib hump).

A randomised controlled trial of an enhanced interdisciplinary community based group program for people with Parkinson’s disease: study rationale and protocol

Parkinson’s disease (PD) is a progressive, chronic neurodegenerative disorder for which there is no known cure. Physical exercise programs may be used to assist with the physical management of PD. Several studies have demonstrated that community based physical therapy programs are effective in reducing physical aspects of disability among people with PD. While multidisciplinary therapy interventions may have the potential to reduce disability and improve the quality of life of people with PD, there is very limited clinical trial evidence to support or refute the use of a community based multidisciplinary or interdisciplinary programs for people with PD. A two group randomized trial is being undertaken within a community rehabilitation service in Brisbane, Australia. Community dwelling adults with a diagnosis of Idiopathic Parkinson’s disease are being recruited. Eligible participants are randomly allocated to a standard exercise rehabilitation group program or an intervention group which incorporates physical, cognitive and speech activities in a multi-tasking framework. Outcomes will be measured at 6-week intervals for a period of six months. Primary outcome measures are the Montreal Cognitive Assessment (MoCA) and the Timed Up and Go (TUG) cognitive test. Secondary outcomes include changes in health related quality of life, communication, social participation, mobility, strength and balance, and carer burden measures. This study will determine the immediate and long-term effectiveness of a unique multifocal, interdisciplinary, dual-tasking approach to the management of PD as compared to an exercise only program. We anticipate that the results of this study will have implications for the development of cost effective evidence based best practice for the treatment of people with PD living in the community.

Microorganisms within human follicular fluid : effects on IVF

Our previous study reported microorganisms in human follicular fluid. The objective of this study was to test human follicular fluid for the presence of microorganisms and to correlate these findings with the in vitro fertilization (IVF) outcomes. In this study, 263 paired follicular fluids and vaginal swabs were collected from women undergoing IVF cycles, with various causes for infertility, and were cultured to detect microorganisms. The cause of infertility and the IVF outcomes for each woman were correlated with the microorganisms detected within follicular fluid collected at the time of trans-vaginal oocyte retrieval. Microorganisms isolated from follicular fluids were classified as: (1) ‘colonizers’ if microorganisms were detected within the follicular fluid, but not within the vaginal swab (at the time of oocyte retrieval); or (2) ‘contaminants’ if microorganisms detected in the vagina at the time of oocyte retrieval were also detected within the follicular fluid. The presence of Lactobacillus spp. in ovarian follicular fluids was associated with embryo maturation and transfer. This study revealed microorganisms in follicular fluid itself and that the presence of particular microorganisms has an adverse affect on IVF outcomes as seen by an overall decrease in embryo transfer rates and pregnancy rates in both fertile and infertile women, and live birth rates in women with idiopathic infertility. Follicular fluid microorganisms are a potential cause of adverse pregnancy outcomes in IVF in both infertile women and in fertile women with infertile male partners.

A pharmacogenomic evaluation of migraine therapy

Migraine is a common idiopathic primary headache disorder with significant mental, physical and social health implications. Accompanying an intense unilateral pulsating head pain other characteristic migraine symptoms include nausea, emesis, phonophobia, photophobia and in approximately 20-30% of migraine cases, neurologic disturbances associated with the aura phase. Although selective serotonin (5-HT) receptor agonists (i.e., 5-HT(1B/1D)) are successful in alleviating migrainous symptoms in < or = 70% of known sufferers, for the remaining 30%, additional migraine abortive medications remain unsuccessful, not tested or yet to be identified. Genetic characterization of the migrainous disorder is making steady progress with an increasing number of genomic susceptibility loci now identified on chromosomes 1q, 4q, 5q, 6p, 11q, 14q, 15q, 17p, 18q, 19p and Xq. The 4q, 5q, 17p and 18q loci involve endophenotypic susceptibility regions for various migrainous symptoms. In an effort to develop individualized pharmacotherapeutics, the identification of these migraine endophenotypic loci may well be the catalyst needed to aid in this goal. In this review the authors discuss the present treatment of migraine, known genomic susceptibility regions and results from migraine (genetic) association studies. The authors also discuss pharmacogenomic considerations for more individualized migraine prophylactic treatments.