Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model. The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count. Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model.
Heterotopic ossification (HO) is perhaps the
single most significant obstacle to independence, functional mobility, and
return to duty for combat-injured veterans of Operation Enduring
Freedom and Operation Iraqi Freedom. Recent research into the cause(s)
of HO has been driven by a markedly higher prevalence seen in these
wounded warriors than encountered in previous wars or following
civilian trauma. To that end, research in both civilian and military
laboratories continues to shed light onto the complex mechanisms
behind HO formation, including systemic and wound specific factors,
cell lineage, and neurogenic inflammation. Of particular interest,
non-invasive
Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal ( Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds.
In order to elucidate the influence of sympathetic nerves on
lumbar radiculopathy, we investigated whether sympathectomy attenuated
pain behaviour and altered the electrical properties of the dorsal
root ganglion (DRG) neurons in a rat model of lumbar root constriction. Sprague-Dawley rats were divided into three experimental groups.
In the root constriction group, the left L5 spinal nerve root was
ligated proximal to the DRG as a lumbar radiculopathy model. In
the root constriction + sympathectomy group, sympathectomy was performed
after the root constriction procedure. In the control group, no
procedures were performed. In order to evaluate the pain relief
effect of sympathectomy, behavioural analysis using mechanical and
thermal stimulation was performed. In order to evaluate the excitability
of the DRG neurons, we recorded action potentials of the isolated
single DRG neuron by the whole-cell patch-clamp method.Objectives
Methods
In a double-blinded randomised controlled trial,
83 patients with primary osteoarthritis of the hip received either
a ceramic-on-metal (CoM) or metal-on-metal (MoM) total hip replacement
(THR). The implants differed only in the bearing surfaces used.
The serum levels of cobalt and chromium and functional outcome scores
were compared pre-operatively and at six and 12 months post-operatively. Data were available for 41 CoM and 36 MoM THRs (four patients
were lost to follow-up, two received incorrect implants). The baseline
characteristics of both cohorts were similar. Femoral head size
measured 36 mm in all but two patients who had 28 mm heads. The
mean serum cobalt and chromium levels increased in both groups,
with no difference noted between groups at six months (cobalt p
= 0.67, chromium p = 0.87) and 12 months (cobalt p = 0.76, chromium
p = 0.76) post-operatively. Similarly, the mean Oxford hip scores,
Western Ontario and McMaster Universities Osteoarthritis index and
University of California, Los Angeles activity scores showed comparable improvement
at 12 months. Our findings indicate that CoM and MoM couplings are associated
with an equivalent increase in serum cobalt and chromium levels,
and comparable functional outcome scores at six and 12-months follow-up.
There is increasing application of bone morphogenetic proteins
(BMPs) owing to their role in promoting fracture healing and bone
fusion. However, an optimal delivery system has yet to be identified.
The aims of this study were to synthesise bioactive BMP-2, combine
it with a novel α-tricalcium phosphate/poly(D,L-lactide-co-glycolide)
(α-TCP/PLGA) nanocomposite and study its release from the composite. BMP-2 was synthesised using an Objectives
Methods
A total of 159 patients (84 women and 75 men,
mean age of 53 (20 to 87)) with subacromial impingement were randomised
to treatment with subacromial injections using lidocaine with one
of hyaluronic acid (51 patients), corticosteroid (53 patients) or
placebo (55Â patients). Patients were followed up for 26 weeks. The
primary outcome was pain on a visual analogue score (VAS), and secondary
outcomes included the Constant Murley score, shoulder pain score,
functional mobility score, shoulder disability questionnaire and
pain-specific disability score. The different outcome measures showed
similar results. After three, six and 12 weeks corticosteroid injections
were superior to hyaluronic acid injections and only at six weeks
significantly better than placebo injections. The mean short-term
reduction in pain on the VAS score at 12 weeks was 7% ( We were not able to show a convincing benefit from hyaluronic
acid injections compared with corticosteroid or placebo injections.
Corticosteroid injections produced a significant reduction in pain
in the short term (three to 12 weeks), but in the long term the
placebo injection produced the best results.
Using a rat model the characteristics of the sensory neurones of the dorsal-root ganglia (DRG) innervating the hip were investigated by retrograde neurotransport and immunohistochemistry. Fluoro-Gold solution (FG) was injected into the left hip of ten rats. Seven days later the DRG from both sides between T12 and L6 were harvested. The number of FG-labelled calcitonin gene-related peptide-immunoreactive or isolectin B4-binding neurones were counted. The FG-labelled neurones were distributed throughout the left DRGs between T13 and L5, primarily at L2, L3, and L4. Few FG-labelled isolectin B4-binding neurones were present in the DRGs of either side between T13 and L5, but calcitonin gene-related peptide-immunoreactive neurones made up 30% of all FG-labelled neurones. Our findings may explain the referral of pain from the hip to the thigh or lower leg corresponding to the L2, L3 and L4 levels. Since most neurones are calcitonin gene-related peptide-immunoreactive peptide-containing neurones, they may have a more significant role in the perception of pain in the hip as peptidergic DRG neurones.
In patients with traumatic brain injury and fractures
of long bones, it is often clinically observed that the rate of bone
healing and extent of callus formation are increased. However, the
evidence has been unconvincing and an association between such an
injury and enhanced fracture healing remains unclear. We performed
a retrospective cohort study of 74 young adult patients with a mean
age of 24.2 years (16 to 40) who sustained a femoral shaft fracture
(AO/OTA type 32A or 32B) with or without a brain injury. All the
fractures were treated with closed intramedullary nailing. The main
outcome measures included the time required for bridging callus
formation (BCF) and the mean callus thickness (MCT) at the final
follow-up. Comparative analyses were made between the 20 patients
with a brain injury and the 54 without brain injury. Subgroup comparisons
were performed among the patients with a brain injury in terms of
the severity of head injury, the types of intracranial haemorrhage
and gender. Patients with a brain injury had an earlier appearance
of BCF
(p <
0.001) and a greater final MCT value (p <
0.001) than
those without. There were no significant differences with respect
to the time required for BCF and final MCT values in terms of the
severity of head injury (p = 0.521 and p = 0.153, respectively),
the types of intracranial haemorrhage (p = 0.308 and p = 0.189,
respectively) and gender (p = 0.383 and
p = 0.662, respectively). These results confirm that an injury to the brain may be associated
with accelerated fracture healing and enhanced callus formation.
However, the severity of the injury to the brain, the type of intracranial
haemorrhage and gender were not statistically significant factors
in predicting the rate of bone healing and extent of final callus formation.
Osteoarthritis is extremely common and many different causes for it have been described. One such cause is abnormal morphology of the affected joint, the hip being a good example of this. For those joints with femoroacetabular impingement (FAI) or developmental dysplasia of the hip (DDH), a link with subsequent osteoarthritis seems clear. However, far from being abnormal, these variants may be explained by evolution, certainly so for FAI, and may actually be normal rather than representing deformity or disease. The animal equivalent of FAI is coxa recta, commonly found in species that run and jump. It is rarely found in animals that climb and swim. In contrast are the animals with coxa rotunda, a perfectly spherical femoral head, and more in keeping with the coxa profunda of mankind. This article describes the evolutionary process of the human hip and its link to FAI and DDH. Do we need to worry after all?
The ideal bearing surface for young patients
undergoing total hip replacement (THR) remains controversial. We report
the five-year results of a randomised controlled trial comparing
the clinical and radiological outcomes of 102 THRs in 91 patients
who were <
 65 years of age. These patients were randomised to
receive a cobalt–chrome on ultra-high-molecular-weight polyethylene,
cobalt–chrome on highly cross-linked polyethylene, or a ceramic-on-ceramic
bearing. In all, 97 hip replacements in 87 patients were available
for review at five years. Two hips had been revised, one for infection
and one for peri-prosthetic fracture. At the final follow-up there were no significant differences
between the groups for the mean Western Ontario and McMaster Universities
osteoarthritis index (pain, p = 0.543; function, p = 0.10; stiffness,
p = 0.99), Short Form-12 (physical component, p = 0.878; mental
component, p = 0.818) or Harris hip scores (p = 0.22). Radiological
outcomes revealed no significant wear in the ceramic group. Comparison of standard and highly cross-linked polyethylene,
however, revealed an almost threefold difference in the mean annual
linear wear rates (0.151 mm/year
Peri-tendinous injection of local anaesthetic,
both alone and in combination with corticosteroids, is commonly performed
in the treatment of tendinopathies. Previous studies have shown
that local anaesthetics and corticosteroids are chondrotoxic, but
their effect on tenocytes remains unknown. We compared the effects
of lidocaine and ropivacaine, alone or combined with dexamethasone,
on the viability of cultured bovine tenocytes. Tenocytes were exposed
to ten different conditions: 1) normal saline; 2) 1% lidocaine;
3) 2% lidocaine; 4) 0.2% ropivacaine; 5) 0.5% ropivacaine; 6) dexamethasone
(dex); 7) 1% lidocaine+dex; 8) 2% lidocaine+dex; 9) 0.2% ropivacaine+dex;
and 10) 0.5% ropivacaine+dex, for 30 minutes. After a 24-hour recovery
period, the viability of the tenocytes was quantified using the
CellTiter-Glo viability assay and fluorescence-activated cell sorting
(FACS) for live/dead cell counts. A 30-minute exposure to lidocaine
alone was significantly toxic to the tenocytes in a dose-dependent
manner, but a 30-minute exposure to ropivacaine or dexamethasone
alone was not significantly toxic. Dexamethasone potentiated ropivacaine tenocyte toxicity at higher
doses of ropivacaine, but did not potentiate lidocaine tenocyte
toxicity. As seen in other cell types, lidocaine has a dose-dependent
toxicity to tenocytes but ropivacaine is not significantly toxic.
Although dexamethasone alone is not toxic, its combination with
0.5% ropivacaine significantly increased its toxicity to tenocytes.
These findings might be relevant to clinical practice and warrant
further investigation.
When transferring tissue regenerative strategies
involving skeletal stem cells to human application, consideration needs
to be given to factors that may affect the function of the cells
that are transferred. Local anaesthetics are frequently used during
surgical procedures, either administered directly into the operative
site or infiltrated subcutaneously around the wound. The aim of
this study was to investigate the effects of commonly used local anaesthetics
on the morphology, function and survival of human adult skeletal
stem cells. Cells from three patients who were undergoing elective hip replacement
were harvested and incubated for two hours with 1% lidocaine, 0.5%
levobupivacaine or 0.5% bupivacaine hydrochloride solutions. Viability
was quantified using WST-1 and DNA assays. Viability and morphology
were further characterised using CellTracker Green/Ethidium Homodimer-1
immunocytochemistry and function was assessed by an alkaline phosphatase
assay. An additional group was cultured for a further seven days
to allow potential recovery of the cells after removal of the local
anaesthetic. A statistically significant and dose dependent reduction in cell
viability and number was observed in the cell cultures exposed to
all three local anaesthetics at concentrations of 25% and 50%, and
this was maintained even following culture for a further seven days. This study indicates that certain local anaesthetic agents in
widespread clinical use are deleterious to skeletal progenitor cells
when studied
This paper summarises the current knowledge on the effects of medullary reaming of long-bone fractures. Following a review of intramedullary vascular physiology, the consequences for vascularity, the autograft effects, the generation of heat, and fat embolism are outlined. Also, alternative reaming techniques are described.
We describe a case of intraneural metastasis of a synovial sarcoma, the first published case of a metastasis of a soft-tissue sarcoma to a peripheral nerve.
Studies describing the effect of body mass index (BMI) on the outcome of total hip replacement have been inconclusive and contradictory. We examined the effect of BMI on medium-term outcome in a cohort of 1617 patients who underwent a primary total hip replacement for osteoarthritis. These patients were followed prospectively for five years with the outcomes of dislocation, revision, duration of surgery and deep and superficial infection studied, as well as collecting Harris hip scores (HHS) and Short-Form 36 (SF-36) questionnaires pre-operatively and at review. A multivariate analysis was performed to see whether BMI is an independent predictor of poor outcome. We found that patients with a BMI of ? 35 kg/m2 have a 4.42 times higher rate of dislocation than those with a BMI <
25 kg/m2. Increasing BMI is also associated with superficial infection and poorer HHS and SF-36 scores at five years. These trends remain significant even when multivariate analysis adjusts for age, gender, prosthesis, operating consultant, pre-operative HHS and SF-36, and comorbidities including diabetes mellitus, cardiac disease and osteoporosis. Despite the increased risks, the five-year outcome scores indicate that obese patients have much to gain from total hip replacement. Thus total hip replacement should not be withheld from patients solely on the grounds of an elevated BMI. However, longer-term follow-up of this cohort is required to establish whether adverse outcomes become more evident with time.
The risk of venous thromboembolism in patients following arthroplasty may be reduced by continuing chemical thromboprophylaxis for up to 35 days post-operatively. This prospective cohort study investigated the compliance of 40 consecutive consenting patients undergoing lower limb arthroplasty with self-administration of a recommended subcutaneous chemotherapeutic agent for six weeks after surgery. Compliance was assessed by examination of the patient for signs of injection, number of syringes used, and a self-report diary at the end of the six-week period. A total of 40 patients, 15 men and 25 women, were recruited. One woman was excluded because immediate post-operative complications prevented her participation. Self-administration was considered feasible in 87% of patients (95% confidence interval (CI) 76 to 98) at the time of discharge. Among this group of 34 patients, 29 (85%) were compliant (95% CI 73 to 97). Patients can learn to self-administer subcutaneous injections of thromboprophylaxis, and compliance with extended prophylaxis to six weeks is good.
A delay in the diagnosis of paediatric acute
and subacute haematogenous osteomyelitis can lead to potentially devastating
morbidity. There are no definitive guidelines for diagnosis, and
recommendations in the literature are generally based on expert
opinions, case series and cohort studies. All articles in the English literature on paediatric osteomyelitis
were searched using MEDLINE, CINAHL, EMBASE, Google Scholar, the
Cochrane Library and reference lists. A total of 1854 papers were
identified, 132 of which were examined in detail. All aspects of
osteomyelitis were investigated in order to formulate recommendations. On admission 40% of children are afebrile. The tibia and femur
are the most commonly affected long bones. Clinical examination,
blood and radiological tests are only reliable for diagnosis in
combination. Most studies were retrospective and there is a need for large,
multicentre, randomised, controlled trials to define protocols for
diagnosis and treatment. Meanwhile, evidence-based algorithms are
suggested for accurate and early diagnosis and effective treatment.
Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.