Group I metabotropic glutamate receptors in spinal cord injury: roles in neuroprotection and the development of chronic central pain

Spinal cord injury (SCI) initiates a cascade of biochemical events that leads to an increase in extracellular excitatory amino acid (EAA) concentrations, which results in glutamate receptor-mediated excitotoxic events. An important division of these glutamate receptors is the metabotropic glutamate receptor (mGluR) class, which is divided into three groups. Of these three groups, group I (mGluR1 and mGluR5) activation can initiate a number of intracellular pathways that lead to increased extracellular EAA concentrations. To evaluate subtypes of group I mGluRs in SCI, we administered AIDA (group I antagonist), LY 367385 (mGluR1 specific antagonist), or MPEP (mGluR5 specific antagonist) by interspinal injection to adult male Sprague-Dawley rats (175-200 g) immediately following injury at T10 with an NYU impactor (12.5-mm drop, 10-g rod, 2 mm in diameter). AIDA- and LY 367385-treated subjects had improved locomotor scores and demonstrated an attenuation in the development of mechanical allodynia as measured by von Frey stimulation of the forelimbs; however, LY 367385 potentiated the development of thermal hyperalgesia. MPEP had no effect on locomotor recovery or mechanical allodynia, but attenuated the development of thermal hyperalgesia. AIDA and LY 367385 treatment resulted in a significant increase in tissue sparing compared to the vehicle-treated group at 4 weeks following SCI. These results suggest that mGluRs play an important role in EAA toxicity and have different acute pathophysiological roles following spinal cord injury.     

Esophegeal replacement in children with AIDS

We report 2 human immunodeficiency virus-positive patients with refractory esophageal strictures secondary to candidiasis. They presented with progressive dysphagia and had suffered from oropharyngeal and/or esophageal candidiasis within the preceding 3 months. Both failed conservative management of these strictures, including systemic antifungal therapy, administration of proton pump inhibitors, and numerous attempts at stricture dilation, ultimately progressing to open transhiatal esophagectomy. Although challenging in the immunocompromised host, successful treatment of these strictures by gastric interposition is achievable with minimal morbidity.     

Characteristics of Vietnamese patients attending an anxiety clinic in Australia and perceptions of the wider Vietnamese community about anxiety

This article examined the causes underlying low utilization of mental health services by Vietnamese immigrants in Australia. Study 1 examined cases of Vietnamese patients who had attended an anxiety disorders clinic, while Study 2 surveyed Vietnamese people in the community on their knowledge and attitudes towards common mental problems. Results from Study 1 showed that Vietnamese patients had significantly higher attrition rates, and presented with a larger number of nonanxiety disorders than their Australian-born counterparts. Study 2 results indicated that many Vietnamese people did not differentiate clearly between the terms 'stress', 'anxiety' and 'depression'. Additionally, many participants felt that there was a generally negative cultural attitude towards people suffering from these problems and the mental health system itself. These outcomes suggest the importance of education for ethnic communities regarding available mental health facilities and treatments offered, as well as specific information on mental illness to help remove stigma.     

Clinical factors and ABCB1 polymorphisms in prediction of antiepileptic drug response: a prospective cohort study

BACKGROUND: The ABCB1 3435C-->T single-nucleotide polymorphism (SNP) or a three-SNP haplotype containing 3435C-->T has been implicated in multidrug resistance in epilepsy in three retrospective case-control studies, but a further three have failed to replicate the association. We aimed to determine the effect of the ABCB1 gene on epilepsy drug response, using a unique large cohort of epilepsy patients with prospectively measured seizure and drug response outcomes. METHODS: The ABCB1 3435C-->T polymorphism and three-SNP haplotype, plus a comprehensive set of tag SNPs across ABCB1 and adjacent ABCB4, were genotyped in a cohort of 503 epilepsy patients with prospectively measured seizure and drug response outcomes. Clinical, demographic, and genetic data were analysed. Treatment outcome was measured in terms of time to 12-month remission, time to first seizure, and time to drug withdrawal due to inadequate seizure control or side-effects. Randomly selected genome-wide HapMap SNPs (n=129) were genotyped in all patients for genomic control. FINDINGS: Number of seizures before treatment was the dominant feature predicting seizure outcome after starting antiepileptic drug therapy, measured by both time to first seizure (hazard ratio 1.34, 95% CI 1.21-1.49, p<0.0001) and time to 12-month remission (0.83, 0.73-0.94, p=0.003). There was no association of the ABCB1 3435C-->T polymorphism, the three-SNP haplotype, or any gene-wide tag SNP with time to first seizure after starting drug therapy, time to 12-month remission, or time to drug withdrawal due to unacceptable side-effects or to lack of seizure control. INTERPRETATION: We found no evidence that ABCB1 common variation influences either seizure or drug withdrawal outcomes after initiation of antiepileptic drug therapy.     

The effect of two- and three-dimensional cell culture on the chondrogenic potential of human adipose-derived mesenchymal stem cells after subcutaneous transplantation with an injectable hydrogel

Articular cartilage is an avascular tissue composed of chondrocytes, a unique cell type responsible for abundant matrix synthesis and maintenance. When damaged, it never heals spontaneously under physiological circumstances. Therefore, the delivery of mesenchymal stem cells using hydrogel has been considered for cartilage repair. This study aims at investigating the influence of in vitro chondrogenic differentiation of human adipose tissue-derived stem cells (hATSCs) on in vivo cartilage formation when associated with a cellulose-based self-setting hydrogel (Si-HPMC). hATSCs were characterized for their proliferation, surface marker expression, and multipotency. The in vitro chondrogenic potential of hATSCs cultured within Si-HPMC in control or chondrogenic medium was evaluated by measuring COL2A1, ACAN, SOX9, and COMP expression by real-time PCR. Alcian blue and type II collagen staining were also performed. To determine whether in vitro chondrogenically differentiated hATSCs may give rise to cartilage in vivo, cells differentiated as a monolayer or in pellets were finally associated with Si-HPMC and implanted subcutaneously into nude mice. Cartilage formation was assessed histologically by alcian blue and type II collagen staining. Our data demonstrate that hATSCs exhibited proliferation and self-renewal. hATSCs also expressed typical stem cell surface markers and were able to differentiate towards the adipogenic, osteogenic, and chondrogenic lineages. Real-time PCR and histological analysis indicated that Si-HPMC enabled chondrogenic differentiation of hATSCs in inductive medium, as demonstrated by increased expression of chondrogenic markers. In addition, histological analysis of implants showed that chondrogenically differentiated hATSCs (monolayers or pellets) have the ability to form cartilaginous tissue, as indicated by the presence of sulphated glycosaminoglycans and type II collagen. This study therefore suggests that an in vitro induction of hATSCs in 2D was sufficient to obtain cartilaginous tissue formation in vivo. Si-HPMC associated with autologous hATSCs could thus be a significant tool for regenerative medicine in the context of cartilage damage.     

Opinions on research and evidence based medicine within the UK osteopathic profession: A thematic analysis of public documents 2003–2009

Background

Very little is known about the attitudes of osteopaths in the UK towards research and evidence based medicine (EBM). It is important to understand the attitudes of osteopaths in order to identify the issues surrounding research and EBM in osteopathy.

Objective

The objective of this study was to collect and thematically analyse public documents (for example editorials, letters, forum threads and essays) from carefully chosen sources, published 2003–2009. Such analysis enables themes and concepts to be drawn out of the data to reflect the hopes, goals, concerns or perceived barriers that osteopaths may have with regards to research and EBM.

Data sources

Two UK osteopathic magazines, two websites for osteopaths and five health databases were searched for data sections. Data sections were selected according to inclusion and exclusion criteria. Magazines were read by the researcher, the two websites’ forum archives were searched using keywords ‘research’ and ‘evidence based medicine,’ and the five databases were searched using MeSH terms ‘osteopathic medicine,’ ‘research’ and ‘evidence based medicine.’

Method

The method was a 6 stage thematic analysis of public documents 2003–2009. Data sections were identified from the public documents using inclusion and exclusion criteria. Sections were broken down into codes and themes were derived from codes using a flexible and reflective process. Higher concepts were then derived from the themes according to relationships and similarities identified between themes.

Results

129 data sections were identified from the 5 sources and coded. 20 themes were derived from the codes, then the themes were further analysed and six concepts were derived from the themes. A final conceptual framework was constructed to represent osteopaths’ opinions on research and EBM. The concepts identified were “uniqueness,” relating to respect for osteopathic principles and Andrew Taylor Still, and the profession maintaining autonomy from mainstream medicine; “position in healthcare,” relating to identifying the need to integrate into mainstream healthcare and gain status and respect from physicians outside of the osteopathic profession; “necessity,” relating to reasons why research should be carried out, and what it should focus on; “barriers,” relating to issues that hinder osteopaths in research such as experience, methods, funding; “solutions,” relating to some suggestions made for overcoming barriers; and “negative impact,” relating to the possible negative consequences that research might have on the profession.

Conclusions

A broad and complex range of issues were identified and osteopaths appear to have differing views about the importance of research and their position in a wider healthcare structure. Preserving osteopathic principles and the profession’s uniqueness is important when considering research and EBM. A fear exists with regards to the impact that research might have on clinical practice. Recommendations for further osteopathic research have been made.     

Perioperative complications in children with Apert syndrome: a review of 509 anesthetics

Objectives: To perform a retrospective, anesthesia case note review in children with Apert Syndrome. Aim: To identify perioperative complications in this group of patients. Background: Apert syndrome is a rare autosomal dominant disorder characterized by craniosynostosis, craniofacial anomalies, and severe symmetrical syndactyly (cutaneous and bony fusion) of the hands and feet. Children with this syndrome require general anesthetics for a number of different operations and procedures. Our institution has records of 71 children with Apert syndrome. Analysis of their general anesthetic records was undertaken, and the incidence of perioperative complications was investigated. Methods: A retrospective case note review was performed on 61 children with Apert syndrome over a 14‐year period. There were a total of 509 general anesthetics administered to these children during this period of time. Results: There were a total of 31 perioperative respiratory complications occurring in 21 patients (6.1% of the total cases). Twenty‐three of these complications were supraglottic airway obstruction (4.5% of total cases). Conclusions: We found there to be a low incidence of major perioperative major complications in this group of patients. Nevertheless, a significant proportion of these children have obstructive sleep apnoea and may develop supraglottic airway obstruction on induction and emergence from anesthesia due to the associated mid‐face anatomical abnormalities.     

Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering

Fetal bone cells were shown to have an interesting potential for therapeutic use in bone tissue engineering due to their rapid growth rate and their ability to differentiate into mature osteoblasts in vitro. We describe hereafter their capability to promote bone repair in vivo when combined with porous scaffolds based on poly(l-lactic acid) (PLA) obtained by supercritical gas foaming and reinforced with 5 wt.% beta-tricalcium phosphate (TCP). Bone regeneration was assessed by radiography and histology after implantation of PLA/TCP scaffolds alone, seeded with primary fetal bone cells, or coated with demineralized bone matrix. Craniotomy critical size defects and drill defects in the femoral condyle in rats were employed. In the cranial defects, polymer degradation and cortical bone regeneration were studied up to 12 months postoperatively. Complete bone ingrowth was observed after implantation of PLA/TCP constructs seeded with human fetal bone cells. Further tests were conducted in the trabecular neighborhood of femoral condyles, where scaffolds seeded with fetal bone cells also promoted bone repair. We present here a promising approach for bone tissue engineering using human primary fetal bone cells in combination with porous PLA/TCP structures. Fetal bone cells could be selected regarding osteogenic and immune-related properties, along with their rapid growth, ease of cell banking and associated safety.