David B. Allan

Identification of bacteria on the surface of clinically infected and non-infected prosthetic hip joints removed during revision arthroplasties by 16S rRNA gene sequencing and by microbiological culture

It has been postulated that bacteria attached to the surface of prosthetic hip joints can cause localised inflammation, resulting in failure of the replacement joint. However, diagnosis of infection is difficult with traditional microbiological culture methods, and evidence exists that highly fastidious or non-cultivable organisms have a role in implant infections. The purpose of this study was to use culture and culture-independent methods to detect the bacteria present on the surface of prosthetic hip joints removed during revision arthroplasties. Ten consecutive revisions were performed by two surgeons, which were all clinically and radiologically loose. Five of the hip replacement revision surgeries were performed because of clinical infections and five because of aseptic loosening. Preoperative and perioperative specimens were obtained from each patient and subjected to routine microbiological culture. The prostheses removed from each patient were subjected to mild ultrasonication to dislodge adherent bacteria, followed by aerobic and anaerobic microbiological culture. Bacterial DNA was extracted from each sonicate and the 16S rRNA gene was amplified with the universal primer pair 27f/1387r. All 10 specimens were positive for the presence of bacteria by both culture and PCR. PCR products were then cloned, organised into groups by RFLP analysis and one clone from each group was sequenced. Bacteria were identified by comparison of the 16S rRNA gene sequences obtained with those deposited in public access sequence databases. A total of 512 clones were analysed by RFLP analysis, of which 118 were sequenced. Culture methods identified species from the genera Leifsonia (54.3%), Staphylococcus (21.7%), Proteus (8.7%), Brevundimonas (6.5%), Salibacillus (4.3%), Methylobacterium (2.2%) and Zimmermannella (2.2%). Molecular detection methods identified a more diverse microflora. The predominant genus detected was Lysobacter, representing 312 (60.9%) of 512 clones analysed. In all, 28 phylotypes were identified: Lysobacter enzymogenes was the most abundant phylotype (31.4%), followed by Lysobacter sp. C3 (28.3%), gamma proteobacterium N4-7 (6.6%), Methylobacterium SM4 (4.7%) and Staphylococcus epidermidis (4.7%); 36 clones (7.0%) represented uncultivable phylotypes. We conclude that a diverse range of bacterial species are found within biofilms on the surface of clinically infected and non-infected prosthetic hip joints removed during revision arthroplasties.

The impact of assuming the primary caregiver role following traumatic spinal cord injury: An interpretative phenomenological analysis of the spouse's experience

This study aimed to explore the lived experience of assuming the primary caregiver role in a group of spouses of individuals living with a traumatic spinal cord injury (SCI) (injuries ranged from paraplegia to quadriplegia). Individual in-depth interviews were conducted with 11 participants who were both the spouse and primary caregiver of an individual with a SCI; of these, 10 were female and 1 was male. All interviews were transcribed verbatim and were subjected to interpretative phenomenological analysis (IPA). Here we present three inter-related master themes: ‘The emotional impact of SCI’; ‘Post-injury shift in relationship dynamics’ and ‘Impact of caregiving on identity’. Regarding the emotional impact of spinal injury, participants reported an almost instantaneous sense of loss, emptiness and grief during the injured persons rehabilitative period and feelings of anxiety were reported in anticipation of their return to the family home. A distinct change in role from spouse and lover to care provider was reported and this ultimately contributed to relationship change and a loss of former identity. The findings are discussed in relation to extant caregiver literature and recommendations for future caregiver support are highlighted.

Development of quantitative and sensitive assessments of physiological and functional outcome during recovery from spinal cord injury: a clinical initiative

The ability to detect physiological changes associated with treatments to effect axonal regeneration, or novel rehabilitation strategies, for spinal cord injury will be challenging using the widely employed American Spinal Injuries Association (ASIA) impairment scales (AIS) for sensory and motor function. Despite many revisions to the AIS standard neurological assessment, there remains a perceived need for more sensitive, quantitative and objective outcome measures. The purpose of Stage 1 of the Clinical Initiative was to develop these tools and then, in Stage 2 to test them for reliability against natural recovery and treatments expected to produce functional improvements in those with complete or incomplete spinal cord injury (SCI). Here we review aspects of the progress made by four teams involved in Stage 2. The strategies employed by the individual teams were (1) application of repetitive transcranial magnetic stimulation (rTMS) to the motor cortex in stable (chronic) SCI with intent to induce functional improvement of upper limb function, (2) a tele-rehabilitation approach using functional electrical stimulation to provide hand opening and grip allowing incomplete SCI subjects to deploy an instrumented manipulandum for hand and arm exercises and to play computer games, (3) weight-assisted treadmill walking therapy (WAT) comparing outcomes in acute and chronic groups of incomplete SCI patients receiving robotic assisted treadmill therapy, and (4) longitudinal monitoring of the natural progress of recovery in incomplete SCI subjects using motor tests for the lower extremity to investigate strength and coordination.

Dynamic oscillatory signatures of central neuropathic pain in spinal cord injury

Central neuropathic pain (CNP) is believed to be accompanied by increased activation of the sensorimotor cortex. Our knowledge of this interaction is based mainly on functional magnetic resonance imaging studies, but there is little direct evidence on how these changes manifest in terms of dynamic neuronal activity. This study reports on the presence of transient electroencephalography (EEG)-based measures of brain activity during motor imagery in spinal cord–injured patients with CNP. We analyzed dynamic EEG responses during imaginary movements of arms and legs in 3 groups of 10 volunteers each, comprising able-bodied people, paraplegic patients with CNP (lower abdomen and legs), and paraplegic patients without CNP. Paraplegic patients with CNP had increased event-related desynchronization in the theta, alpha, and beta bands (16–24 Hz) during imagination of movement of both nonpainful (arms) and painful limbs (legs). Compared to patients with CNP, paraplegics with no pain showed a much reduced power in relaxed state and reduced event-related desynchronization during imagination of movement. Understanding these complex dynamic, frequency-specific activations in CNP in the absence of nociceptive stimuli could inform the design of interventional therapies for patients with CNP and possibly further understanding of the mechanisms involved. Perspective This study compares the EEG activity of spinal cord–injured patients with CNP to that of spinal cord–injured patients with no pain and also to that of able-bodied people. The study shows that the presence of CNP itself leads to frequency-specific EEG signatures that could be used to monitor CNP and inform neuromodulatory treatments of this type of pain.

Human mesenchymal stem cells isolated from olfactory biopsies but not bone enhance CNS myelination in vitro

Spinal cord injury (SCI) is a devastating condition with limited capacity for repair. Cell transplantation is a potential strategy to promote SCI repair with cells from the olfactory system being promising candidates. Although transplants of human olfactory mucosa (OM) are already ongoing in clinical trials, the repair potential of this tissue remains unclear. Previously, we identified mesenchymal‐like stem cells that reside in the lamina propria (LP‐MSCs) of rat and human OM. Little is known about these cells or their interactions with glia such as olfactory ensheathing cells (OECs), which would be co‐transplanted with MSCs from the OM, or endogenous CNS glia such as oligodendrocytes. We have characterized, purified, and assessed the repair potential of human LP‐MSCs by investigating their effect on glial cell biology with specific emphasis on CNS myelination in vitro. Purified LP‐MSCs expressed typical bone marrow MSC (BM‐MSC) markers, formed spheres, were clonogenic and differentiated into bone and fat. LP‐MSC conditioned medium (CM) promoted oligodendrocyte precursor cell (OPC) and OEC proliferation and induced a highly branched morphology. LP‐MSC‐CM treatment caused OEC process extension. Both LP and BM‐MSCs promoted OPC proliferation and differentiation, but only myelinating cultures treated with CM from LP and not BM‐MSCs had a significant increase in myelination. Comparison with fibroblasts and contaminating OM fibroblast like‐cells showed the promyelination effect was LP‐MSC specific. Thus LP‐MSCs harvested from human OM biopsies may be an important candidate for cell transplantation by contributing to the repair of SCI.

Role of peripheral quantitative computed tomography in identifying disuse osteoporosis in paraplegia

ObjectiveDisuse osteoporosis is a major long-term health consequence of spinal cord injury (SCI) that still needs to be addressed. Its management in SCI should begin with accurate diagnosis, followed by targeted treatments in the most vulnerable subgroups. We present data quantifying disuse osteoporosis in a cross-section of the Scottish paraplegic population to identify subgroups with lowest bone mineral density (BMD).Materials and methodsForty-seven people with chronic SCI at levels T2-L2 were scanned using peripheral quantitative computed tomography at four tibial sites and two femoral sites, at the Queen Elizabeth National Spinal Injuries Unit, Glasgow (UK). At the distal epiphyses, trabecular BMD (BMDtrab), total BMD, total bone cross-sectional area (CSA) and bone mineral content (BMC) were determined. In the diaphyses, cortical BMD, total bone CSA, cortical CSA and BMC were calculated. Bone, muscle and fat CSAs were estimated in the lower leg and thigh.ResultsBMDtrab decreased exponentially with time since injury at different rates in the tibia and femur. At most sites, female paraplegics had significantly lower BMC, total bone CSA and muscle CSA than male paraplegics. Subjects with lumbar SCI tended to have lower bone values and smaller muscle CSAs than in thoracic SCI.ConclusionAt the distal epiphyses of the tibia and femur, there is generally a rapid and extensive reduction in BMDtrab after SCI. Female subjects, and those with lumbar SCI, tend to have lower bone values than males or those with thoracic SCI, respectively.

Cardiorespiratory and power adaptations to stimulated cycle training in paraplegia

PURPOSE The extent to which cardiorespiratory fitness and cycling power can be improved in individuals with paraplegia by progressive, high-volume, home-based, electrically stimulated (ES) cycle training was investigated using a novel, sensitive method and protocol that allowed high-resolution power output analyses to be performed for the first time in ES cycling. METHODS Nine male and two female individuals with paraplegia trained progressively at home for up to five 60-min sessions x wk(-1) for 12 months. Peak power and cardiorespiratory parameters were estimated during quarterly feedback-controlled incremental work rate tests in the laboratory. RESULTS Cycle training endurance increased from 10 to 60 min of continuous pedaling for all subjects. Peak power output (POpeak) increased by 132% (P = 0.001), peak oxygen uptake (VO2peak) increased by 56% (P < 0.001), and oxygen pulse increased by 34% (P = 0.002). All significant adaptations occurred during the first 6 months of training when training load was progressive and duration compliance (90%) and frequency compliance (88%) were at their highest. A strong positive relationship between the total training duration and the magnitude of improvements in both POpeak (r2 = 0.84, P < 0.001) and VO2peak (r2 = 0.52, P= 0.012) was found during the first 6 months only. CONCLUSIONS High-volume, home-based ES cycle training using the current training and the ES strategies can significantly improve cardiorespiratory fitness and cycling power output in paraplegia but only while training is progressive. The training plateau reached by 6 months may be physiological in nature or due to the ES strategy used.

The metabolic cost of passive walking during robotics-assisted treadmill exercise

BACKGROUND We are investigating the potential of robotics-assisted treadmill technology as a mode of exercise in people with spinal cord injury (SCI). People with incomplete SCI can actively contribute to this form of exercise, but in the clinical setting they often walk passively in the system. It is not known whether in doing so they are meeting the recommended guidelines for increasing cardiopulmonary fitness. OBJECTIVE The aims of this study were twofold: to characterise the intensity of passive walking during robotics-assisted treadmill exercise (RATE) in incomplete SCI; and to determine if this intensity meets the recommended guidelines for cardiopulmonary training in this population. METHODS 10 subjects with incomplete SCI twice performed an exercise test on a robotics-assisted treadmill. The test comprised a period of passive walking and a ramp phase to the limit of tolerance. Oxygen uptake VO(2) heart rate (HR) were continuously measured. RESULTS VO(2) during passive exercise was on average 1.4 times higher than resting VO(2R), but this was only 29% of peak VO(2) (VO(2 peak))(range 16-43%). Relative to rest, passive VO(2) (VO(2P) was only 12% of VO(2 peak). HR did not increase from rest to passive walking (81 ± 10 bpm to 81 ± 13 bpm respectively). The HR associated with passive walking was on average 50% of peak HR (HR(peak)) (161 ± 13 bpm). Test-retest reliability was moderate for VO(2R) (R=0.62) and resting HR (HR(R)) (R=0.68), high for VO(2P) (R=0.81), passive HR (HR(P)) (R=0.87) and HR(peak) (R=0.88), and very high (R=0.95) for VO(2 peak). Only HR(p) differed significantly between tests (p=0.029). CONCLUSIONS The intensity of passive walking during RATE is low and is insufficient to increase cardiopulmonary fitness in people with SCI. Subjects must actively contribute to the exercise in order to achieve the recommended training intensity.

Adjustment and Coping in Spousal Caregivers Following a Traumatic Spinal Cord Injury: An Interpretative Phenomenological Analysis

Semi-structured interviews were conducted with 11 spousal caregivers to people with a traumatic spinal cord injury and were subjected to interpretative phenomenological analysis (IPA). Here, we present two inter-related master themes: (1) coping with the spousal caregiver role; and (2) putting the pieces back together again. Within these, the analysis describes how regular venting of emotion, social support and focusing on the positive aspects of the situation all promoted coping. Adjustment was reportedly hindered by the introduction of paid caregivers as this represented a loss of privacy and power for the participants. The findings are discussed in relation to the wider literature and recommendations for future caregiver support are highlighted.

Changing demographics of spinal cord injury over a 20-year period: a longitudinal population-based study in Scotland.

Study design:A retrospective cohort study.Objectives:To review demographic trends in traumatic spinal cord injury (TSCI) and non-traumatic spinal cord injury (NTSCI).Setting:The Queen Elizabeth National Spinal Injuries Unit (QENSIU), sole provider of treatment for TSCI in Scotland; a devolved region of the UK National Health Service.Methods:A retrospective review of the QENSIU database was performed between 1994 and 2013. This database includes demographic and clinical data from all new TSCI patients in Scotland, as well as patients with severe NTSCI.Results:Over this 20-year period there were 1638 new cases of TSCI in Scotland; 75.2% occurring in males. TSCI incidence increased non-significantly (13.3 per million population to 17.0), while there were significant increases in mean age at time of TSCI (44.1–52.6 years), the proportion of TSCIs caused by falls (41–60%), the proportion of TSCIs resulting in an American Spinal Injury Association Impairment Scale score of C and D on admission (19.7–28.6% and 34.5–39.5%, respectively) and the proportion of cervical TSCIs (58.4–66.3%). The increase in cervical TSCI was specifically due to an increase in C1–C4 lesions (21.7–31.2%). NTSCI patients (n=292) were 5 years older at injury, more likely to be female (68.1% male) and had a range of diagnoses.Conclusion:This study supports the suggestion that demographic profiles in SCI are subject to change. In this population, of particular concern is the increasing number of older patients and those with high level tetraplegia, due to their increased care needs. Prevention programmes, treatment pathways and service provision need to be adjusted for optimum impact, improved outcome and long-term care for their target population.