Postoperative pain relief using intermittent intrapleural analgesia following thoracoscopic anterior correction for progressive adolescent idiopathic scoliosis

Background Thoracoscopic anterior scoliosis instrumentation is a safe and viable surgical option for corrective fusion of progressive adolescent idiopathic scoliosis (AIS) and has been performed at our centre on 205 patients since 2000. However, there is a paucity of literature reporting on or examining optimum methods of analgesia following this type of surgery. A retrospective study was designed to present the authors’ technique for delivering intermittent local anaesthetic boluses via an intrapleural catheter following thoracoscopic scoliosis surgery; report the pain levels that may be expected and any adverse effects associated with the use of intrapleural analgesia, as part of a combined postoperative analgesia regime. Methods Records for 32 patients who underwent thoracoscopic anterior correction for AIS were reviewed. All patients received an intrapleural catheter inserted during surgery, in addition to patient-controlled opiate analgesia and oral analgesia. After surgery, patients received a bolus of 0.25% bupivacaine every four hours via the intrapleural catheter. Patient’s perceptions of their pain control was measured using the visual analogue pain scale scores which were recorded before and after local anaesthetic administration and the quantity and time of day that any other analgesia was taken, were also recorded. Results 28 female and four male patients (mean age 14.5 ± 1.5 years) had a total of 230 boluses of local anaesthetic administered in the 96 hour period following surgery. Pain scores significantly decreased following the administration of a bolus (p < 0.0001), with the mean pain score decreasing from 3.66 to 1.83. The quantity of opiates via patient-controlled analgesia after surgery decreased steadily between successive 24 hours intervals after an initial increase in the second 24 hour period when patients were mobilised. One intrapleural catheter required early removal due to leakage; there were no other associated complications with the intermittent intrapleural analgesia method. Conclusions Local anaesthetic administration via an intrapleural catheter is a safe and effective method of analgesia following thoracoscopic anterior scoliosis correction. Post-operative pain following anterior thoracic scoliosis surgery can be reduced to ‘mild’ levels by combined analgesia regimes. Keywords: Adolescent idiopathic scoliosis; Thoracoscopic anterior spinal fusion; Anterior fusion; Intrapleural analgesia; Endoscopic anterior surgery; Pain relief; Scoliosis surgery

A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura

Migraine with aura is a common, debilitating, recurrent headache disorder associated with transient and reversible focal neurological symptoms. A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord potassium channel (TRESK, encoded by KCNK18), in pain pathways and general anaesthesia. We therefore examined whether TRESK is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. Here we report a frameshift mutation, F139WfsX24, which segregates perfectly with typical migraine with aura in a large pedigree. We also identified prominent TRESK expression in migraine-salient areas such as the trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes a complete loss of TRESK function and that the mutant subunit suppresses wild-type channel function through a dominant-negative effect, thus explaining the dominant penetrance of this allele. These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target.

Regional chromosomal assignment of human renin gene to 1q12→qter and use in linkage studies in Charcot-Marie-Tooth disease

The gene for renin, previously mapped to human chromosome 1, was further localized to 1q12 → qter using human-mouse somatic cell hybrid DNAs. The renin DNA probe used (λ HR5) could detect a HindIII restriction fragment length polymorphism. When used in studies of 12 informative families, no linkage could be found between the renin and Charcot-Marie-Tooth disease. Furthermore, an association of any renin allele with hypertension was not apparent.

Chromosome I linkage studies in Charcot-Marie-Tooth neuropathy type I

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder of peripheral nerve. The gene for CMT1 was originally localized to chromosome 1 by linkage to the Duffy blood group, but it has since been shown that not all CMT1 pedigrees show this linkage. We report here the results of linkage studies using five chromosome 1 markers - Duffy (Fy), antithrombin III (AT3), renin (REN), β-nerve growth factor (NGFB), and salivary amylase (AMY1) - in 16 CMT1 pedigrees. The total lod scores exclude close linkage of CMT1 to any of these markers. However, individual families show probable linkage of CMT1 to Duffy, AT3, and/or AMY1. No linkage was indicated with REN or NGFB. These results indicate that possible location of a CMT1 gene between the AMY1 and AT3 loci at p21 and q23, respectively, on chromosome 1 and support the theory that there is at least one other CMT1 gene.

Heterogeneity evidence and linkage studies on Charcot-Marie-Tooth disease

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder originally localized to chromosome 1 by linkage to the Duffy blood group. Studies have since shown that the disorder may be heterogeneous, as not all families show this linkage. We tested genetic heterogeneity by the HOMOG computer program in 15 CMT1 pedigrees informative for Duffy. We detected no evidence for heterogeneity in this sample, but when we combined results with previously published lod scores, heterogeneity was statistically significant. Twelve of the 15 families studied did not show linkage to Duffy. We found six of these families to be informative for a chromosome 19 marker, apolipoprotein CII(ApoC2). Despite a previous report showing probable linkage of a non-Duffy-linked CMT1 pedigree to two chromosome 19 markers, we did not detect significant linkage of ApoC2 to CMT1 in these families.

Isolation and use of chromosome 1 probes for linkage studies on Charcot-Marie-Tooth disease

Nine probes were isolated from a human chromosome 1 enriched library and mapped to regions of chromosome 1 using somatic cell hybrid lines. One clone, LR67, which mapped 1q12→q23 detected a BglI RFLP. This probe, as well as 4 other known chromosome 1 markers, α-spectrin, Factor XIIIB, DR10 and DR78, were used for linkage studies in 15 Charcot-Marie-Tooth disease (CMT1) families. Close linking of CMT1 to any of the 5 markers was not indicated. Total lod scores excluded linkage of CMT1 to LR67 and to DR10 at 5 cM or less, to DR78 and 10 cM or less, α-spectrin at 15 cM or less and Factor XIIIB at 20 cM or less. Possible linkage, however, was shown between LR67 and CMT1 at a distance of 30 cM. Also linkage at a distance of 5 cM was detected between this probe and α-spectrin.

DNA probes in Charcot-Marie-Tooth neuropathy

Results of Duffy (Fy) linkage confirm genetic heterogeneity in Charcot-Marie-Tooth disease type 1 (CMT1). Of 11 families informative for Fy, four showed probable linkage with CMT1, seven showed probable non-linkage and two showed definite non-linkage. These results suggest that Fy linked CMT1 may be less common than previously thought. These results combined with those of another DNA probe for the antithrombin III gene confirm that there are at least two gene loci for CMT1, termed 1A and 1B.

Evaluating the dosimetric effect of treatment-induced changed in virally mediated head and neck cancer patients

Introduction Patients with virally mediated head and neck cancer (VMHNC) often present with advanced nodal disease that is highly radioresponsive as demonstrated by tumour and nodal regression during treatment. The resultant changes may impact on the planned dose distribution and so adversely affect the therapeutic ratio. The aim of this study was to evaluate the dosimetric effect of treatment-induced anatomical changes in VMHNC patients who had undergone a re-plan. Methods Thirteen patients with virally mediated oropharyngeal or nasopharyngeal cancer who presented for definitive radiotherapy between 2005 and 2010 and who had a re-plan generated were investigated. The dosimetric effect of anatomical changes, was quantified by comparing dose volume histograms (DVH) of primary and nodal gross target volumes and organs at risk (OAR), including spinal cord and parotid glands, from the original plan and a comparison plan. Results Eleven 3DCRT and 2 IMRT plans were evaluated. Dose to the spinal cord and brainstem increased by 4.1% and 2.6%, respectively. Mean dose to the parotid glands also increased by 3.5%. In contrast, the dose received by 98% of the primary and nodal gross tumour volumes decreased by 0.15% and 0.3%, respectively when comparing the initial treatment plan to the comparison plan. Conclusion In this study, treatment-induced anatomical changes had the greatest impact on OAR dose with negligible effect on the dose to nodal gross tumour volumes. In the era of intensity modulated radiotherapy (IMRT), accounting for treatment-induced anatomical changes is important as focus is placed on minimising the acute and long-term side effects of treatment.

Orthopaedics and trauma Queensland annual report 2012

Orthopaedics and Trauma Queensland, the Centre for Research and Education in Musculoskeletal Disorders, is an internationally recognised research group that continues to develop its reputation as an international leader in research and education. It provides a stimulus for research, education and clinical application within the international orthopaedic and trauma communities. Orthopaedics and Trauma Queensland develops and promotes the innovative use of engineering and technology, in collaboration with surgeons, to provide new techniques, materials, procedures and medical devices. Its integration with clinical practice and strong links with hospitals ensure that the research will be translated into practical outcomes for patients. The group undertakes clinical practice in orthopaedics and trauma and applies core engineering skills to challenges in medicine. The research is built on a strong foundation of knowledge in biomedical engineering, and incorporates expertise in cell biology, mathematical modelling, human anatomy and physiology and clinical medicine in orthopaedics and trauma. New knowledge is being developed and applied to the full range of orthopaedic diseases and injuries, such as knee and hip replacements, fractures and spinal deformities.

How Can Models of Motor Control Be Useful for Understanding Low Back Pain?

Introduction. The purpose of this chapter is to address the question raised in the chapter title. Specifically, how can models of motor control help us understand low back pain (LBP)? There are several classes of models that have been used in the past for studying spinal loading, stability, and risk of injury (see Reeves and Cholewicki (2003) for a review of past modeling approaches), but for the purpose of this chapter we will focus primarily on models used to assess motor control and its effect on spine behavior. This chapter consists of 4 sections. The first section discusses why a shift in modeling approaches is needed to study motor control issues. We will argue that the current approach for studying the spine system is limited and not well-suited for assessing motor control issues related to spine function and dysfunction. The second section will explore how models can be used to gain insight into how the central nervous system (CNS) controls the spine. This segues segue nicely into the next section that will address how models of motor control can be used in the diagnosis and treatment of LBP. Finally, the last section will deal with the issue of model verification and validity. This issue is important since modelling accuracy is critical for obtaining useful insight into the behavior of the system being studied. This chapter is not intended to be a critical review of the literature, but instead intended to capture some of the discussion raised during the 2009 Spinal Control Symposium, with some elaboration on certain issues. Readers interested in more details are referred to the cited publications.

Characterisation of Polycaprolatone-Based Scaffold Plus Recombinant Human Morphogenetic Protein - 2 (RHBMP-2) in an Ovine Thoracic Spine Model

This thesis represents a step forward in the development of a pre-clinical model investigating a suitable substitute for host bone for use in human spinal fusion. By way of an animal model, it examines the biological performance of a novel bone graft substitute comprised of a combination of a custom-designed biodegradable material and biologics.

Comparison between electrically-evoked and voluntary wrist movements on sensorimotor and prefrontal cortical activation : A multi-channel time domain fNIRS study

Neuromuscular electrical stimulation (NMES) has been consistently demonstrated to improve skeletal muscle function in neurological populations with movement disorders, such as poststroke and incomplete spinal cord injury (Vanderthommen and Duchateau, 2007). Recent research has documented that rapid, supraspinal central nervous system reorganisation/neuroplastic mechanisms are also implicated during NMES (Chipchase et al., 2011). Functional neuroimaging studies have shown NMES to activate a network of sub-cortical and cortical brain regions, including the sensorimotor (SMC) and prefrontal (PFC) cortex (Blickenstorfer et al., 2009; Han et al., 2003; Muthalib et al., 2012). A relationship between increase in SMC activation with increasing NMES current intensity up to motor threshold has been previously reported using functional MRI (Smith et al., 2003). However, since clinical neurorehabilitation programmes commonly utilise NMES current intensities above the motor threshold and up to the maximum tolerated current intensity (MTI), limited research has determined the cortical correlates of increasing NMES current intensity at or above MTI (Muthalib et al., 2012). In our previous study (Muthalib et al., 2012), we assessed contralateral PFC activation using 1-channel functional near infrared spectroscopy (fNIRS) during NMES of the elbow flexors by increasing current intensity from motor threshold to greater than MTI and showed a linear relationship between NMES current intensity and the level of PFC activation. However, the relationship between NMES current intensity and activation of the motor cortical network, including SMC and PFC, has not been clarified. Moreover, it is of scientific and clinical relevance to know how NMES affects the central nervous system, especially in comparison to voluntary (VOL) muscle activation. Therefore, the aim of this study was to utilise multi-channel time domain fNIRS to compare SMC and PFC activation between VOL and NMESevoked wrist extension movements.

Bone matters in lung cancer

Background: Bone metastases are a significant and undertreated clinical problem in patients with advanced lung cancer. Design: We reviewed the incidence of bone metastases and skeletal-related events (SREs) in patients with lung cancer and examined the burden on patients' lives and on health care systems. Available therapies to improve survival and lessen the impact of SREs on quality of life (QoL) were also investigated. Results: Bone metastases are common in lung cancer; however, owing to short survival times, data on the incidences of SREs are limited. As with other cancers, the costs associated with treating SREs in lung cancer are substantial. Bisphosphonates reduce the frequency of SREs and improve measures of pain and QoL in patients with lung cancer; however, nephrotoxicity is a common complication of therapy. Denosumab, a recently approved bone-targeted therapy, is superior to zoledronic acid in increasing the time to first on-study SRE in patients with solid tumours, including lung cancer. Additional roles of bone-targeted therapies beyond the prevention of SREs are under investigation. Conclusions: With increasing awareness of the consequences of SREs, bone-targeted therapies may play a greater role in the management of patients with lung cancer, with the aim of delaying disease progression and preserving QoL. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Evaluating the use of online synchronous communication to enhance learning in statistics

According to social constructivists, learners are active participants in constructing new knowledge in a social process where they interact with others. In these social settings teachers or more knowledgeable peers provide support. This research study investigated the contribution that an online synchronous tutorial makes to support teaching and learning of undergraduate introductory statistics offered by an Australian regional university at a distance. The introductory statistics course which served as a research setting in this study was a requirement of a variety of programs at the University, including psychology, business and science. Often students in these programs perceive this course to be difficult and irrelevant to their programs of study. Negative attitudes and associated anxiety mean that students often struggle with the content. While asynchronous discussion forums have been shown to provide a level of interaction and support, it was anticipated that online synchronous tutorials would offer immediate feedback to move students forward through ―stuck places.‖ At the beginning of the semester the researcher offered distance students in this course the opportunity to participate in a weekly online synchronous tutorial which was an addition to the usual support offered by the teaching team. This tutorial was restricted to 12 volunteers to allow sufficient interaction to occur for each of the participants. The researcher, as participant-observer, conducted the weekly tutorials using the University's interactive online learning platform, Wimba Classroom, whereby participants interacted using audio, text chat and a virtual whiteboard. Prior to the start of semester, participants were surveyed about their previous mathematical experiences, their perceptions of the introductory statistics course and why they wanted to participate in the online tutorial. During the semester, they were regularly asked pertinent research questions related to their personal outcomes from the tutorial sessions. These sessions were recorded using screen capture software and the participants were interviewed about their experiences at the end of the semester. Analysis of these data indicated that the perceived value of online synchronous tutorial lies in the interaction with fellow students and a content expert and with the immediacy of feedback given. The collaborative learning environment offered the support required to maintain motivation, enhance confidence and develop problemsolving skills in these distance students of introductory statistics. Based on these findings a model of online synchronous learning is proposed.

Targeting histone deacetylases for the treatment of immune, endocrine and metabolic disorders

The 'histone code' is a well-established hypothesis describing the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as histone acetyltransferases or HATs, and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The proinflammatory environment is increasingly being recognised as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential & current development of histone deacetylases for the treatment of diseases for which a proinflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the proinflammatory environment. © 2009 Bentham Science Publishers Ltd.