In order to clarify the role of cytokines in the remodelling of the grafted tendon for ligament reconstruction we compared the responses to interleukin (IL)-1β, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β1 of extrinsic fibroblasts infiltrating the frozen-thawed patellar tendon in rats with that of the normal tendon fibroblasts, in regard to the gene expression of matrix metalloproteinase (MMP)-13, using Northern blot analysis. We also examined, immunohistologically, the local expression of IL-1β, PDGF-BB, and TGF-β1 in fibroblasts infiltrating the frozen-thawed patellar tendon. Northern blot analysis showed that fibroblasts derived from the patellar tendon six weeks after the freeze-thaw procedure
We used a biodegradable mesh to convert an acetabular defect into a contained defect in six patients at total hip replacement. Their mean age was 61 years (46 to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the strength retention and hydrolytic in vitro degradation properties of the implants were studied in the laboratory over a two-year period. A successful clinical outcome was determined by the radiological findings and the Harris hip score. All the patients had a satisfactory outcome and no mechanical failures or other complications were observed. No protrusion of any of the impacted grafts was observed beyond the mesh. According to our preliminary laboratory and clinical results the biodegradable mesh is suitable for augmenting uncontained acetabular defects in which the primary stability of the implanted acetabular component is provided by the host bone. In the case of defects of the acetabular floor this new application provides a safe method of preventing graft material from protruding excessively into the pelvis and the mesh seems to tolerate bone-impaction grafting in selected patients with primary and revision total hip replacement.
We retrospectively reviewed 30 two-stage revision
procedures in 28 patients performed for fungal peri-prosthetic joint
infection (PJI) after a primary total knee replacement. Patients were
followed for at least two years or until the infection recurred.
The mean follow-up for patients who remained free of infection was
4.3 years (2.3 to 6.1). Overall, 17 patients were assessed as American
Society of Anesthesiologists grade 3 or 4. The surgical protocol included
removal of the infected implant, vigorous debridement and insertion
of an articulating cement spacer. This was followed by at least
six weeks of antimicrobial treatment and delayed reimplantation
in all patients. The mean interval between removal of the prosthesis
and reimplantation was 9.5 weeks (6 to 24). After reimplantation,
patients took antifungal agents orally for a maximum of six months. Fungal PJIs can be treated successfully by removal of all infected
material, appropriate antimicrobial treatment and delayed reimplantation.
The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.
This prospective study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients (41 men and 37 women) with a revision total knee or hip replacement. The mean age at the time of operation was 64.0 years (19 to 90). Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement. The white blood cell count, the erythrocyte sedimentation rate and levels of C-reactive protein, interleukin-6, procalcitonin and tumour necrosis factor (TNF)-α were measured in blood samples before operation. The diagnostic cut-off values were determined by Received Operating Characteristic curve analysis. C-reactive protein (>
3.2 md/dl) and interleukin-6 (>
12 pg/ml) have the highest sensitivity (0.95). Interleukin-6 is less specific than C-reactive protein (0.87 The combination of C-reactive protein and interleukin-6 measurement provide excellent screening tests for infection of a deep implant. A highly specific marker such as procalcitonin and pre-operative aspiration of the joint might be useful in identifying patients with true positive C-reactive protein and/or interleukin-6 levels.
Between 1986 and 2002, 42 patients with synchronous multifocal osteosarcoma were treated with two different protocols of neoadjuvant chemotherapy. When feasible, the primary and secondary tumours were excised as a combined procedure. After initial chemotherapy 26 patients were excluded from simultaneous excision of all their secondary bone lesions as their disease was too advanced. In 12 patients only isolated excision of the primary lesion was possible. For 16 patients simultaneous operations were conducted to excise the primary and secondary lesions. This involved two supplementary sites in 15 patients and four additional sites in one patient. Of these, 15 attained remission but 12 relapsed and died (11 within two years). Three patients remained disease-free at five, six and 17 years. The histological response to pre-operative chemotherapy of the primary and secondary lesions was concordant in 13 of the 16 patients who underwent simultaneous operations at more than one site. The prognosis for synchronous multifocal osteosarcoma remains poor despite combined chemotherapy and surgery. The homogeneous histological responses in a large proportion of the primary and secondary lesions implies that synchronous multifocal osteosarcoma tumours are not multicentric in origin, but probably represent bone-to-bone metastases from a single tumour.
The rate and mode of early failure in 463 Birmingham hip resurfacings in a two-centre, multisurgeon series were examined. Of the 463 patients two have died and three were lost to follow-up. The mean radiological and clinical follow-up was for 43 months (6 to 90). We have revised 13 resurfacings (2.8%) including seven for pain, three for fracture, two for dislocation and another for sepsis. Of these, nine had macroscopic and histological evidence of metallosis. The survival at five years was 95.8% (95% confidence interval (CI) 94.1 to 96.8) for revision for all causes and 96.9% (95% CI 95.5 to 98.3) for metallosis. The rate of metallosis related revision was 3.1% at five years. Risk factors for metallosis were female gender, a small femoral component, a high abduction angle and obesity. We do not advocate the use of the Birmingham Hip resurfacing procedure in patients with these risk factors.
Rupture of the tendo Achillis is a common injury
with a rising incidence. Traditionally the key question following
this injury has been whether or not to operate. However a contemporary
Cochrane review highlighted that the method of rehabilitation may
also have an important contribution to the outcome. Since this review,
various early weight-bearing rehabilitation protocols have been
described. Currently evidence points to the use of early functional
rehabilitation, regardless of operative or non-operative management.
However, there is no consensus on which exact functional rehabilitation
protocol should be used. Future research should be directed towards
improving our understanding of how the different rehabilitative
components interact in the tendo Achillis as it heals.
We compared the biological characteristics of extrinsic fibroblasts infiltrating the patellar tendon with those of normal, intrinsic fibroblasts in the normal tendon Proliferation and invasive migration into the patellar tendon was significantly slower for infiltrative fibroblasts than for normal tendon fibroblasts. Flow-cytometric analysis indicated that expression of α5β1 integrin at the cell surface was significantly lower in infiltrative fibroblasts than in normal tendon fibroblasts. The findings suggest that cellular proliferation and invasive migration of fibroblasts into the patellar tendon after necrosis are inferior to those of the normal fibroblasts. The inferior intrinsic properties of infiltrative fibroblasts may contribute to a slow remodelling process in the grafted tendon after ligament reconstruction.
Surgical marking during tendon surgery is often used for technical
and teaching purposes. This study investigates the effect of a gentian
violet ink marker pen, a common surgical marker, on the viability
of the tissue and cells of tendon.
Objectives
Methods
The need for bone tissue supplementation exists in a wide range
of clinical conditions involving surgical reconstruction in limbs,
the spine and skull. The bone supplementation materials currently
used include autografts, allografts and inorganic matrix components;
but these pose potentially serious side-effects. In particular the
availability of the autografts is usually limited and their harvesting
causes surgical morbidity. Therefore for the purpose of supplementation
of autologous bone graft, we have developed a method for autologous
extracorporeal bone generation. Human osteoblast-like cells were seeded on porous granules of
tricalcium phosphate and incubated in osteogenic media while exposed
to mechanical stimulation by vibration in the infrasonic range of
frequencies. The generated tissue was examined microscopically following
haematoxylin eosin, trichrome and immunohistochemical staining.Objectives
Methods
Human articular cartilage samples were retrieved from the resected material of patients undergoing total knee replacement. Samples underwent automated controlled freezing at various stages of preparation: as intact articular cartilage discs, as minced articular cartilage, and as chondrocytes immediately after enzymatic isolation from fresh articular cartilage. Cell viability was examined using a LIVE/DEAD assay which provided fluorescent staining. Isolated chondrocytes were then cultured and Alamar blue assay was used for estimation of cell proliferation at days zero, four, seven, 14, 21 and 28 after seeding. The mean percentage viabilities of chondrocytes isolated from group A (fresh, intact articular cartilage disc samples), group B (following cryopreservation and then thawing, after initial isolation from articular cartilage), group C (from minced cryopreserved articular cartilage samples), and group D (from cryopreserved intact articular cartilage disc samples) were 74.7% (95% confidence interval (CI) 73.1 to 76.3), 47.0% (95% CI 43 to 51), 32.0% (95% CI 30.3 to 33.7) and 23.3% (95% CI 22.1 to 24.5), respectively. Isolated chondrocytes from all groups were expanded by the following mean proportions after 28 days of culturing: group A ten times, group B 18 times, group C 106 times, and group D 154 times. This experiment demonstrated that it is possible to isolate viable chondrocytes from cryopreserved intact human articular cartilage which can then be successfully cultured.
Patients with infected arthroplasties are normally
treated with a two-stage exchange procedure using polymethylmethacrylate
bone cement spacers impregnated with antibiotics. However, spacers
may act as a foreign body to which micro-organisms may adhere and
grow. In this study it was hypothesised that subclinical infection may
be diagnosed with sonication of the surface biofilm of the spacer.
The aims were to assess the presence of subclinical infection through
sonication of the spacer at the time of a second-stage procedure,
and to determine the relationship between subclinical infection
and the clinical outcome. Of 55 patients studied, 11 (20%) were
diagnosed with subclinical infection. At a mean follow-up of 12
months (interquartile range 6 to 18), clinical failure was found in
18 (32.7%) patients. Of the patients previously diagnosed with subclinical
infection, 63% (7 of 11) had failed compared with 25% (11 of 44)
of those without subclinical infection (odds ratio 5.25, 95% confidence
interval 1.29 to 21.4, p = 0.021). Sonication of the biofilm of
the surface of the spacer is useful in order to exclude subclinical infection
and therefore contributes to improving the outcome after two-stage
procedures.
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.
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
Infection of a total hip replacement (THR) requires component removal and thorough local debridement. Usually, long-term antibiotic treatment in conjunction with a two-stage revision is required. This may take several months. One-stage revision using antibiotic-loaded cement has not gained widespread use, although the clinical and economic advantages are obvious. Allograft bone may be impregnated with high levels of antibiotics, and in revision of infected THR, act as a carrier providing a sustained high local concentration. We performed 37 one-stage revision of infected THRs, without the use of cement. There were three hips which required further revision because of recurrent infection, the remaining 34 hips (92%) stayed free from infection and stable at a mean follow-up of 4.4 years (2 to 8). No adverse effects were identified. Incorporation of bone graft was comparable with unimpregnated grafts. Antibiotic-impregnated allograft bone may enable reconstruction of bone stock, insertion of an uncemented implant and control of infection in a single operation in revision THR for infection.
Nutritional osteomalacia is a metabolic bone disorder common among the Asian female immigrant population in the United Kingdom. We describe the case of a female of Asian origin, who was found to have a unilateral undisplaced pseudofracture of the neck of the femur during pregnancy. Although not operated on the fracture was treated successfully with calcium and vitamin D supplement therapy. Within one month of treatment, the bone pain subsided and she was able to bear full weight. Subsequent radiological follow-up showed the pseudofracture to have healed sufficiently with no evidence of avascular necrosis. There should be a high index of suspicion of this disease, particularly among Asian patients presenting with persistent and non-specific musculoskeletal pain.
Wear of metal-on-metal bearings causes elevated levels of cobalt and chromium in blood and body fluids. Metal-on-metal bearings have two distinct wear phases. In the early phase, the wear rate is high. Later, it decreases and the bearing enters a steady-state phase. It is expected that as the wear rates decline, the level of cobalt detected in plasma will also decrease. We studied the baseline and exercise-related cobalt rise in 21 patients (13 men and eight women) with a mean age of 54 years (38 to 80) who had undergone successful hip resurfacing at a mean of 44 months (10 to 96) earlier. Our results showed that circulating baseline cobalt levels were not significantly correlated with the time since implantation (r = 0.08, p = 0.650). By contrast, the exercise-related cobalt rise was directly correlated with the inclination angle of the acetabular component (r = 0.47, p = 0.032) and inversely correlated with the time since implantation (r = −0.5, p = 0.020). Inclination of the acetabular component should be kept less than 40° to decrease the production of wear debris.
We examined cultured osteoblasts derived from paired samples from the greater tuberosity and acromion from eight patients with large chronic tears of the rotator cuff. We found that osteoblasts from the tuberosity had no apparent response to mechanical stimulation, whereas those derived from the acromion showed an increase in alkaline phosphatase activity and nitric oxide release which is normally a response of bone cells to mechanical strain. By contrast, we found that cells from both regions were able to respond to dexamethasone, a well-established promoter of osteoblastic differentiation, with the expected increase in alkaline phosphatase activity. Our findings indicate that the failure of repair of the rotator cuff may be due, at least in part, to a compromised capacity for mechanoadaptation within the greater tuberosity. It remains to be seen whether this apparent decrease in the sensitivity of bone cells to mechanical stimulation is the specific consequence of the reduced load-bearing history of the greater tuberosity in these patients.
We attempted to characterise the biological quality
and regenerative potential of chondrocytes in osteochondritis dissecans
(OCD). Dissected fragments from ten patients with OCD of the knee
(mean age 27.8 years (16 to 49)) were harvested at arthroscopy.
A sample of cartilage from the intercondylar notch was taken from
the same joint and from the notch of ten patients with a traumatic
cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes
were extracted and subsequently cultured. Collagen types 1, 2, and
10 mRNA were quantified by polymerase chain reaction. Compared with
the notch chondrocytes, cells from the dissecate expressed similar
levels of collagen types 1 and 2 mRNA. The level of collagen type
10 message was 50 times lower after cell culture, indicating a loss
of hypertrophic cells or genes. The high viability, retained capacity
to differentiate and metabolic activity of the extracted cells suggests
preservation of the intrinsic repair capability of these dissecates.
Molecular analysis indicated a phenotypic modulation of the expanded
dissecate chondrocytes towards a normal phenotype. Our findings
suggest that cartilage taken from the dissecate can be reasonably
used as a cell source for chondrocyte implantation procedures.