Efficacy and safety of vertebroplasty for treatment of painful osteoporotic vertebral fractures: a randomised controlled trial [ACTRN012605000079640]

Background: Vertebroplasty is a promising but as yet unproven treatment for painful osteoporotic vertebral fractures. It involves radiographic-guided injection of various types of bone cement directly into the vertebral fracture site. Uncontrolled studies and two controlled quasi-experimental before-after studies comparing volunteers who were offered treatment to those who refused it, have suggested an early benefit including rapid pain relief and improved function. Conversely, several uncontrolled studies and one of the controlled before-after studies have also suggested that vertebroplasty may increase the risk of subsequent vertebral fractures, particularly in vertebrae adjacent to treated levels or if cement leakage into the adjacent disc has occurred. As yet, there are no completed randomised controlled trials of vertebroplasty for osteoporotic vertebral fractures. The aims of this participant and outcome assessor-blinded randomised placebo-controlled trial are to i) determine the short-term efficacy and safety (3 months) of vertebroplasty for alleviating pain and improving function for painful osteoporotic vertebral fractures; and ii) determine its medium to longer-term efficacy and safety, particularly the risk of further fracture over 2 years.

Design: A double-blind randomised controlled trial of 200 participants with one or two recent painful osteoporotic vertebral fractures. Participants will be stratified by duration of symptoms (< and ≥ 6 weeks), gender and treating radiologist and randomly allocated to either the treatment or placebo. Outcomes will be assessed at baseline, 1 week, 1, 3, 6, 12 and 24 months. Outcome measures include overall, night and rest pain on 10 cm visual analogue scales, quality of life measured by the Assessment of Quality of Life, Osteoporosis Quality of Life and EQ-5D questionnaires; participant perceived recovery on a 7-point ordinal scale ranging from 'a great deal worse' to 'a great deal better'; disability measured by the Roland-Morris Disability Questionnaire; timed 'Up and Go' test; and adverse effects. The presence of new fractures will be assessed by radiographs of the thoracic and lumbar spine performed at 12 and 24 months.

Discussion: The results of this trial will be of major international importance and findings will be immediately translatable into clinical practice.

Trial registration: Australian Clinical Trial Register # [ACTRN012605000079640]

Postural neck pain : an investigation of habitual sitting posture, perception of 'good' posture and cervicothoracic kinaesthesia

Impairments of cervico-cephalic kinaesthesia and habitual forward head posture have been considered important in the aetiology of postural neck pain, yet these factors have not been specifically examined in a homogeneous clinical population. The objective of this study was to compare the habitual sitting posture (HSP), perception of good posture and postural repositioning error (PRE) of the cervico-thoracic (CT) spine in individuals with postural neck pain, with a matched group of asymptomatic subjects. Twenty-one subjects with postural neck pain and 22 asymptomatic control subjects were recruited into the study. An optical motion analysis system was used to measure the HSP and perceived ‘good’ sitting posture. PRE was measured over six trials where the subject attempted to replicate their self-selected ‘good’ posture. There was no difference between the groups in the HSP but significant differences were identified in the perception of ‘good’ posture. Posture repositioning error was higher for the head posture variables than for CT and shoulder girdle variables in both groups. However, there was no significant difference in posture repositioning error between groups for any of the posture measures. The findings suggest that individuals with postural neck pain may have a different perception of ‘good’ posture, but no significant difference in HSP or kinaesthetic sensibility compared with matched asymptomatic subjects.

Patients and nurses' perspective on oxygen therapy : a qualitative study

Aim. This paper is a report of a study to describe patients' and nurses' perspectives on oxygen therapy.
Background. Failure to correct significant hypoxaemia may result in cardiac arrest, need for mechanical ventilation or death. Nurses frequently make clinical decisions about the selection and management of low-flow oxygen therapy devices. Better understanding of patients' and nurses' experiences of oxygen therapy could inform clinical decisions about oxygen administration using low-flow devices.
Methods. Face-to-face interviews with a convenience sample of 37 adult patients (17 cardio-thoracic: 20 medical surgical) and 25 intensive care unit nurses were conducted from February 2007 to September 2007. Interviews were audio-taped, transcribed verbatim and then analysed using a thematic analysis approach.
Findings. The patients identified three key factors that underpinned their compliance with oxygen therapy: (i) device comfort; (ii) ability to maintain activities of daily living; and (iii) therapeutic effect. The nurses identified factors, such as: (i) therapeutic effect, (ii) issues associated with compliance, (iii) strategies to optimize compliance, (iv) familiarity with device, (v) triggers for changing oxygen therapy devices, as being key to the effective management of oxygen therapy.
Conclusion. Differences between the patients' and nurses' perspective of oxygen therapy illustrate the variety of factors that impact on effective oxygen administration. Further research should seek to provide a further in-depth understanding of the current oxygen administration practices of nurses and the patient factors that enhance or hinder effectiveness of oxygen therapy. Detailed information about nurse and patient factors that influence oxygen therapy will inform a sound evidence base for nurses' oxygen administration decisions.

Ontogeny of putative GABAergic neurons and their receptors in the nervous system of the crayfish Cherax destructor

Inhibitory neurons exert control the expression of many aspects of behaviour by regulating the effectiveness of excitatory neural function. By comparison with excitatory neural systems, relatively little is known about the development of inhibitory neurons and the influence which these neurons exert on the development of other neural systems. Two issues which relate to the development of inhibitory neurons are of particular interest. First, a paradox arises when inhibitory neurons are considered in terms of modern models of synaptic development which involve activity-dependent mechanisms of synaptic plasticity. Second, there is some evidence that inhibitory neurotransmitters may act in a special trophic manner during the early development of nervous systems. Investigations of these issues would be greatly facilitated in a neural system in which it was possible to experimentally control aspects of the development of individual pre- and postsynaptic cells. The aim of the results presented in this thesis was to characterise the normal development of one such system: the GABAergic inhibitory system of the Australian freshwater crayfish, Cherax destructor. The ontogeny of the inhibitory neurotransmitter GABA across the embryonic period of 30% to 100% development was investigated using immunohistochemical techniques. GABA-like immunoreactive cells and fibres were first detected in the embryonic brain region. The expression of GABA-like immunoreactivity progressed along a rostro-caudal gradient, with GABA-like immunoreactive cells being detected in the most anterior thoracic ganglia at 45% development and in all ganglia by 65% development. GABA-like immunoreactive fibres were evident in peripheral nerves as early as 55% development and ramified extensively throughout the neuropil of the nervous system by 65% development. By contrast, immunoreactivity to the primary excitatory neurotransmitter, glutamate, was not detected until 60-65% development. Glutamate-like immunoreactivity at 60-65% development was evident only in the form of punctate staining in the midline of the ventral nerve cord. Cell body staining was observed only at 90% development and was restricted to only a few cells on the periphery of the ventral nerve cord. Radio-labelled ligand binding methods and autoradiography were used to study the expression of putative GABA receptors in the Cherax embryos from 30% to 100% development. Specific binding was evident in the earliest embryos studies at 30% development. There was an initial increase in binding from 30% to 40% development, followed by a dramatic drop to almost zero binding at 50-55% development. This was followed by a gradual increase in binding levels with age, reaching a plateau at 85% development. Preliminary pharmacological evaluation of binding indicated that at least three GABA receptor types were expressed during embryonic development. Methods for culturing, dissociated neural tissues explanted form Cherax embryos at 85% development were established. The success of cultures was demonstrated by neurite extension, and neuronal networks in which neurons appeared to form connections with other neurons and with explanted muscle cells after two days in culture. Immunohistochemical studies demonstrated that some explanted neurons expressed GABA-like immunoreactivity within two days of explanting. These studies have provided a comprehensive description of the development of GABAergic neurons and their receptors in Cherax destructor embryos. The very early expression of GABA-like immunoreactivity, coupled with the early onset of specific GABA binding, strongly indicates that the GABAergic neurons are functional and able to exert an effect on other cells during much of the period of nervous system development in crayfish embryos. These results support the hypothesis that inhibitory neurons may play an important role as regulators of the overall process of assembly and maturation of the nervous system and provide a substantial basis for future experimental studies in which the specific action of inhibitory neurons on the development of discrete components of the crayfish nervous system may be investigated.

Control of ovarian development in the yabby (Cherax destructor)

A study under controlled conditions of ovarian development and rematuration in the yabby (Cherax destructot) was undertaken. The purpose of the study was to improve fundamental understanding of the reproductive biology of the species and provide a basis for application to hatchery management in culture. A review was made of the current status of yabby culture in Australia and the present understanding of reproductive biology of decapod Crustacea. The review emphasised factors controlling several aspects of ovarian development, in particular the processes of vitellogenesis. The subsequent study was designed within the context of current hatchery practice and was based on existing knowledge of decapod reproduction, The sexual differentiation of the yabby after hatching was investigated by serial histological sections, and experiments were carried out to investigate the possibility of sex reversal of males. Most of this Investigation was concerned with removing the influence of the androgenic gland in directing male development, with the intent of observing the development of the elementary gonadal tissue into ovary. It was found that in contrast to other crustacean species, the sex of the yabby becomes fixed before the development of external secondary sexual characteristics, and before the androgenic gland can be discerned. Ovarian tissue developed in females at less than 8 weeks after hatching. A preliminary examination was undertaken for feminising parasites in gonadal tissue of a hermaphrodite yabby. Investigation of the ovary after spawning demonstrated that whilst the female was held under constant conditions of temperature and photoperiod, little rematuration occurred. Except for generation of previtellogenic oocytes during the first two days, the gonaciosomatic index remained low for up to 5 months after spawning. If the temperature of the female was reduced to 10°C and maintained constant, the previtellogenic oocytes were partially resorbed over a three week period. Rematuration then commenced, albeit at a low rate because of the reduced temperature, A method for standardising gonadosomatic indices was developed which took into account differences in hepatopancreatic nutrient reserves of individuals and loss of one or more appendages. This part of the study also considered constraints to rematuration and developed a method of accounting for differences in the ability of females to remature after spawning. Experiments were carried out to investigate the effect of crowding and temperature manipulation on initiating ovarian rematuration and to determine the rate of rematuration at 22°C once initiated. The duration of low temperature had no effect on rematuration; an overnight cooling was sufficient to initiate the process, Rematuration to the end of stage 2 vltellogenesis was substantially complete within 10 days. Crowding of females suppressed rematuration, but less than ideal water quality was not found to have any effect. The presence of a male initiated rematuration at a similar rate, but also led to stage 3 vitetlogenesis and spawning. A study was made of the pheromonal influence of the male through water borne factors without success. Rematuration could not be induced in ovigerous females. The literature review indicated that ovarian rematuration was under the control of an ovary stimulating hormone produced by the thoracic nerve ganglia. Attempts were therefore made to stimulate ovarian rematuration by incorporating the thoracic nerve into the diet of females. Attempts were also made to induce the release of ovary stimulating hormone from the thoracic nerve with 5-hydroxytryptamine, and also with octopamine. No effects were found, but a significant difference between the neurophysiology of the yabby and northern hemisphere crayfish was observed, and the implications of this finding are discussed. The study did not produce any conclusive evidence of an ovary stimulating hormone for the yabby. A model of ovarian rematuration which collects the findings of the experimental investigations was developed, and was used to suggest a hatchery broodstock management protocol. This model differs from existing models in that rematuration triggers and nutritional status are considered.

Polyethyleneterephthalate provides superior retention of endothelial cells during shear stress compared to polytetrafluoroethylene and pericardium

Background

Polyethyleneterephthalate (PET) and polytetrafluoroethylene (PTFE) are polymers successfully used as large diameter arterial grafts for peripheral vascular surgery. However, these prosthetic grafts are rarely used for coronary bypass surgery because of their low patency rates. Endothelialisation of the lumenal surface of these materials may improve their patency. This study aimed to compare the endothelialisation of PET, PTFE and pericardium by examining their seeding efficiency over time and the effect of various shear stresses on retention of endothelial cells.

Methods


Ovine endothelial cells at 4 × 105 cells/cm2 were seeded onto PET, PTFE and pericardium, and cultured for 1–168 hours. Cell coverage was determined via en face immunocytochemistry and cell retention was quantified after being subjected to shear stresses ranging from 0.018 to 0.037 N/m2 for 15, 30 and 60 minutes.

Results

Endothelial cells adhered to all of the materials one hour post-seeding. PET exhibited better cell retention rate, ranging from 66.9 ± 5.6% at 0.018 N/m2 for 15 min to 44.7 ± 1.9% at 0.037 N/m2 for 60 minutes, when compared to PTFE and pericardium (p < 0.0001, three-way ANOVA).

Conclusion

PET shows superior retention of endothelial cells during shear stress compare to PTFE and pericardium.

Isoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women

The possibility that the heightened cardiovascular risk associated with the menopause can be reduced by increasing dietary isoflavone intake was tested in 17 women by measuring arterial compliance, an index of the elasticity of large arteries such as the thoracic aorta. Compliance diminishes with age and menopause. An initial 3- to 4-week run-in period and a 5-week placebo period were followed by two 5-week periods of active treatment with 40 mg and then 80 mg isoflavones derived from red clover containing genistein, daidzein, biochanin, and formononetin in 14 and 13 women, respectively, with 3 others serving as placebo controls throughout. Arterial compliance, measured by ultrasound as a pressure (carotid artery) and volume (outflow into aorta) relationship, was determined after each period; plasma lipids were measured twice during each period. Urinary output of isoflavones was also determined. Arterial compliance rose by 23% relative to that during the placebo period with the 80-mg isoflavone dose and slightly less with the 40-mg dose (mean6SEM: placebo, 19.761.5; 40 mg, 23.760.7; 80 mg, 24.46 1.4). In the three women receiving continuous placebo, compliance was 16 6 2.2, similar to that during the run-in period for the remaining subjects (17 6 2.1). ANOVA showed a significant (P 5 , 0.001) difference between treatments; by Bonferroni multiple comparisons and by paired t test, differences were significant between placebo and 40- and 80-mg isoflavone doses (by paired t test: P50.039 for placebo vs. 40 mg; P 5 0.018 for placebo vs. 80 mg). Plasma lipids were not significantly affected. An important cardiovascular risk factor, arterial compliance, which diminishes with menopause, was significantly improved with red clover isoflavones. As diminished compliance leads to systolic hypertension and may increase left ventricular work, the findings indicate a potential new therapeutic approach for improved cardiovascular function after menopause.

Implementation of a management guideline aimed at minimizing the severity of primary graft dysfunction after lung transplant

Objective
Primary graft dysfunction, a severe form of lung injury that occurs in the first 72 hours after lung transplant, is associated with morbidity and mortality. We sought to assess the impact of an evidence-based guideline as a protocol for respiratory and hemodynamic management.

Methods
Preoperative and postoperative data for patients treated per the guideline (n = 56) were compared with those of a historical control group (n = 53). Patient data such as ratio of arterial Po2 to inspired oxygen fraction, central venous pressure, cumulative fluid balance, vasopressor dose, and serum urea and creatinine were measured and documented at specific times. Primary outcome was severity of primary graft dysfunction within the first 72 hours.

Results
Primary graft dysfunction grade was progressively lower in patients treated after introduction of the guideline (P = .01). Lower postoperative fluid balances (P = .01) and vasopressor doses (P = .007) were seen, with no associated renal dysfunction. There were no differences in duration of mechanical ventilation or mortality. Nonadherence to the guideline occurred in 10 cases (18%).

Conclusions
Implementation of an evidence-based guideline for managing respiratory and hemodynamic status is feasible and safe and was associated with reduction in severity of primary graft dysfunction. Further studies are required to determine whether such a guideline would lead to a consistent reduction in severity of primary graft dysfunction at other institutions. Creation of a protocol for postoperative care provides a template for further studies of novel therapies or management strategies for primary graft dysfunction.

Glutathione peroxidase-1 reduces influenza A virus-induced lung inflammation

Oxidative stress caused by excessive reactive oxygen species production is implicated in influenza A virus–induced lung disease. Glutathione peroxidase (GPx)-1 is an antioxidant enzyme that may protect lungs from  such damage. The objective of this study was to determine if GPx-1 protects the lung against influenza A virus–induced lung inflammation in vivo.

Correlation between a self-administered walk test and a standardised Six Minute Walk Test in adults

This study was undertaken to assess the correlation between a self-administered, adapted Six Minute Walk Test (the Home-Heart-Walk) and the standard Six Minute Walk Test based on the American Thoracic Society guideline. A correlational study was conducted at a university campus in Sydney, Australia. Thirteen healthy volunteers underwent the Home-Heart-Walk and the standard Six Minute Walk Test on a single occasion. The distance that participants walked during the two tests was assessed using Pearson's correlation. The correlation between the Home-Heart-Walk and the Six Minute Walk Test distance was 0.81. The Home-Heart-Walk distance was highly correlated to the standard Six Minute Walk Test distance in this study. This relationship provides confidence for further research in populations to facilitate monitoring and evaluation.

Validation and development of a clinical prediction rule in clinically suspected community-acquired pneumonia

To develop a mathematical model to predict the probability of having community-acquired pneumonia and to evaluate an already developed prediction rule that has not been validated in a clinical scenario.