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1.  Connexin-mimetic peptide Gap 27 decreases osteoclastic activity 
Background
Bone remodelling is dependent on the balance between bone resorbing osteoclasts and bone forming osteoblasts. We have shown previously that osteoclasts contain gap-junctional protein connexin-43 and that a commonly used gap-junctional inhibitor, heptanol, can inhibit osteoclastic bone resorption. Since heptanol may also have some unspecific effect unrelated to gap-junctional inhibition we wanted to test the importance of gap-junctional communication to osteoclasts using a more specific inhibitor.
Methods
A synthetic connexin-mimetic peptide, Gap 27, was used to evaluate the contribution of gap-junctional communication to osteoclastic bone resorption. We utilised the well-characterised pit-formation assay to study the effects of the specific gap-junctional inhibitor to the survival and activity of osteoclasts.
Results
Gap 27 caused a remarked decrease in the number of both TRAP-positive mononuclear and multinucleated rat osteoclasts cultured on bovine bone slices. The decrease in the cell survival seemed to be restricted to TRAP-positive cells, whereas the other cells of the culture model seemed unaffected. The activity of the remaining osteoclasts was found to be diminished by measuring the percentage of osteoclasts with actin rings of all TRAP-positive cells. In addition, the resorbed area in the treated cultures was greatly diminished.
Conclusions
On the basis of these results we conclude that gap-junctional communication is essential for the action of bone resorbing osteoclasts and for proper remodelling for bone.
doi:10.1186/1471-2474-2-10
PMCID: PMC61034  PMID: 11747476
2.  Long term in-vivo studies of a photo-oxidized bovine osteochondral transplant in sheep 
Background
Articular cartilage has limited capacity to repair. Defects greater than 3 mm heal with formation of inferior fibrous cartilage. Therefore, many attempts have been made to find the ideal graft for larger cartilage lesions. Different grafts, such as untreated or cryopreserved osteochondral transplants, have been used with variable success.
Methods
Photo-oxidized osteochondral grafts were implanted in both femoral condyles of one ovine knee. Untreated xenogeneic and autogeneic grafts served as controls. Three groups of 8 sheep each were formed and they were sacrificed 6, 12 or 18 months after surgery.
Results
The macroscopic evaluation of the condyle and graft showed a well-maintained cartilage surface in most grafts at all time points. However, the host cartilage matrix deteriorated considerably in all xenogeneic, most autogeneic and fewer of the photo-oxidized grafts at 12 and 18 months, respectively. The blue colour of the photo-oxidized grafts resulting from the process of photo-oxidation was visible in all grafts at 6 months, had diminished at 12 months and had completely disappeared at 18 months after surgery. Histologically a loss of matrix staining was almost never noticed in untreated xenografts, transiently at 6 months in photo-oxidized grafts and increased at 12 and 18 months. Fusion between graft and host cartilage could be seen in photo-oxidized grafts at 12 and 18 months, but was never seen in autografts and xenografts.
Conclusions
The photo-oxidation of osteochondral grafts and its use as transplant appears to have a beneficial effect on cartilage and bone remodelling. Osteochondral grafts pre-treated with photo-oxidation may be considered for articular cartilage replacement and therefore may delay artificial joint replacements in human patients.
doi:10.1186/1471-2474-2-9
PMCID: PMC61033  PMID: 11747477
3.  Polyomyositis and myocarditis associated with acquired toxoplasmosis in an immunocompetent girl 
Background
Acquired toxoplasmosis more frequently goes unrecognized. Immunocompetent adults and adolescents with primary infection are generally asymptomatic, but symptoms may include malaise, fever, and lymphadenopathy. By contrast, immunocompromised patients may experience severe manifestations including encephalitis and multisystem organ failure.
Case presentation
We report a case of polymyositis and myocarditis in a 13-year old immunocompetent girl with toxoplasmosis. The patient presented with proximal muscle weakness, dysphagia, palms and soles rash and elevated serum levels of muscle enzymes, with liver and myocardial involvement. The diagnosis of toxoplasmosis was confirmed by serology. The patient was treated with prednisolone and had an excellent outcome. During a follow-up period of four years no relapses occurred and antibody levels to the T. gondii significantly decreased.
Conclusions
Although several previous cases of toxoplasmosis occuring in association with polymyositis have been described in the literature such a wide spectrum of acute toxoplasmosis is rather unusual in immunocompetent adolescents. The relationship between T. gondii and polymyositis remains obscure. Appropriate investigation should be performed in every case of polymyositis not only for the appropriate treatment but also for further elucidation of this relationship.
doi:10.1186/1471-2474-2-8
PMCID: PMC65052  PMID: 11818029
4.  Hormone replacement therapy and prevention of vertebral fractures: a meta-analysis of randomised trials 
Background
Hormone replacement therapy (HRT) is often seen as the treatment of choice for preventing fractures in women. We undertook a recent meta-analysis of randomised trials which suggested that HRT reduced non-vertebral fractures by 30%. In this analysis we extend that analysis to vertebral fractures.
Methods
We searched the main electronic databases until the end of August 2001. We sought all randomised controlled trials (RCTs) of HRT where women had been randomised to at least 12 months of HRT or to no HRT.
Results
We found 13 RCTs. Overall there was a 33% reduction in vertebral factures (95% confidence interval (CI) 45% to 98%).
Conclusions
This review and meta-analysis showed a significant reduction in vertebral fractures associated with HRT use.
doi:10.1186/1471-2474-2-7
PMCID: PMC59898  PMID: 11716794
5.  Dynamic compression nail: A preliminary report 
Background
Interlocking nailing, which has become the method of choice for treating fractures of the femoral and tibial shafts, still lacks ability to provide the important contact-compression at the fracture. An intramedullary compression nail is described, which provides axial compression at the fracture site with tightening of the specially designed distal interlocking screw. This uses the same principle as dynamic compression plating.
Methods
The study included 11 femoral and tibial nailings performed for various clinical applications such as acute fractures, non-unions and malunions.
Results
All the fractures attained radiological union, with good skeletal continuity across the fracture, within an average time of 13 weeks in fresh fractures and 18 weeks in non-unions.
Conclusions
Active compression through intramedullary compression nailing has great utility for treating non-unions where it provides greater degree of impaction of its irregular ends. This may prove greatly advantageous to the fracture union through increased stability and the osteogenic potential, particularly when utilized in combination with the small diameter unreamed nails.
doi:10.1186/1471-2474-2-6
PMCID: PMC59672  PMID: 11701095
6.  Time course of muscle soreness following different types of exercise 
Background
Post-exercise muscle soreness is a dull, aching sensation that follows unaccustomed muscular exertion. Primarily on the basis of previous laboratory-based research on eccentric exercise, soreness is usually said to follow an inverted U-shaped curve over time, peaking 24 – 48 hours after exercise. As such, it is often described as "delayed-onset" muscle soreness. In a study of long-distance runners, soreness seemed to peak immediately and then reduce gradually over time. The study is a secondary analysis of clinical trial data that aims to determine whether the time course of soreness following a natural exercise, long-distance running, is different from that following a laboratory-based exercise, bench-stepping.
Methods
This is a reanalysis of data from three previous clinical trials. The trials included 400 runners taking part in long-distance races and 82 untrained volunteers performing a bench-stepping test. Subjects completed a Likert scale of muscle soreness every morning and evening for the five days following their exercise.
Results
Interaction between trial and time is highly significant, suggesting a different time course of soreness following running and bench-stepping. 45% of subjects in the bench-stepping trial experienced peak soreness at the third or fourth follow-up (approximately 36 – 48 hours after exercise) compared to only 14% of those in the running trial. The difference between groups is robust to multivariate analysis incorporating possible confounding variables.
Conclusion
Soreness in runners following long-distance running follows a different time course to that in untrained individuals undertaking bench-stepping. Research on exercise taking place in the laboratory context does not necessarily generalize to exercise undertaken by trained athletes when engaged in their chosen sport.
doi:10.1186/1471-2474-2-5
PMCID: PMC59671  PMID: 11701094
7.  Recruitment curve of the soleus H-reflex in chronic back pain and lumbosacral radiculopathy 
Background
Needle EMG may be negative in mild or predominantly sensory lumbosacral radiculopathies. In such cases, an increase in the latency of the soleus H-reflex is a useful diagnostic criterion for establishing sensory fiber compromise at the S1 root level. However, if clinical signs of radicular involvement are lacking, the latency of the H-reflex is normal. We therefore studied the recruitment curve of the soleus H-reflex to investigate whether a change in the electrical threshold for eliciting the H-reflex might be a more sensitive criterion for detecting subclinical S1 root dysfunction.
Methods
Clinical and electrophysiological findings from 26 patients with chronic back pain and radiculopathy were compared with data obtained from 40 healthy subjects.
Results
An increase in the mean H-reflex threshold was the only abnormal electrophysiological finding in patients with no clinical sign of root injury (58%). A decrease in the mean H-reflex amplitude and a prolongation of H-reflex latency was observed in patients with radicular signs (42%). In both patients groups, F-wave and needle EMG studies were normal. No radiological evidence of S1 root compression was found.
Conclusions
The study of the recruitment curve of the soleus H-reflex may be usefully associated to F-wave and needle EMG studies to detect possible S1 root dysfunction in mild lumbosacral radiculopathies. An increase in H-threshold may be the earliest abnormality in the absence of focal neurological signs.
doi:10.1186/1471-2474-2-4
PMCID: PMC60003  PMID: 11722799
8.  MCMV induces neointima in IFN-γR-/- mice: Intimal cell apoptosis and persistent proliferation of myofibroblasts 
Background
CMV infections have been linked to vasculopathies like atherosclerosis and Scleroderma. CMV infects vascular endothelium with intermittent shedding of the virus and the development of latency.
Methods
We adopted a model of arteritis, developed by Presti et al. (1998), triggered by murine cytomegalovirus (MCMV) infection. Our studies focused on neointima formation. Groups of mice include: 1) immunocompetent 129S, 2) immunocompetent 129S receiving whole body irradiation and MCMV, 3) IFN-γR-/- receiving MCMV, and 4) IFN-γR-/- receiving MCMV and whole body irradiation.
Results
Mice were inoculated with MCMV (5 x 104 or 1 x 105 PFU's) by i.p. injection; hearts and abdominal aortas were collected and histopathology evaluated. Infected immunocompetent animals exhibited widespread perivascular inflammation, which subsided by 8 weeks. Intimal pathology was not observed in any control group. Immunocompetent animals receiving MCMV and irradiation developed mild to moderate intimal lesions associated with medial and adventitial inflammation. IFN-γR-/- mice infected for 4 months and receiving whole body irradiation 2 months after infection developed pathology characterized by extensive adventitial and medial infiltrate and significant neointima, suggesting that infection and immunosuppression were co-requisites of neointima formation. Immunohistochemical analysis revealed myofibroblasts as a major component of neointima. The disease is characterized by up-regulation of growth factors (TGF-β1, PDGF-A and B). Apoptosis was detected in the intimal layer of affected aortas. Active proliferation of myofibroblasts and infiltrating cells was also detected.
Conclusion
These results indicate that CMV infections may lead to intimal injury that results in the formation of neointima characteristic of autoimmune vasculopathies.
doi:10.1186/1471-2474-2-3
PMCID: PMC37542  PMID: 11518546
9.  Delayed union of femoral fractures in older rats:decreased gene expression 
Background
Fracture healing slows with age. While 6-week-old rats regain normal bone biomechanics at 4 weeks after fracture, one-year-old rats require more than 26 weeks. The possible role of altered mRNA gene expression in this delayed union was studied. Closed mid-shaft femoral fractures were induced followed by euthanasia at 0 time (unfractured) or at 1, 2, 4 or 6 weeks after fracture in 6-week-old and 12-15-month-old Sprague-Dawley female rats. mRNA levels were measured for osteocalcin, type I collagen α1, type II collagen, bone morphogenetic protein (BMP)-2, BMP-4 and the type IA BMP receptor.
Results
For all of the genes studied, the mRNA levels increased in both age groups to a peak at one to two weeks after fracture. All gene expression levels decreased to very low or undetectable levels at four and six weeks after fracture for both age groups. At four weeks after fracture, the younger rats were healed radiographically, but not the older rats.
Conclusions
(1) All genes studied were up-regulated by fracture in both age groups. Thus, the failure of the older rats to heal promptly was not due to the lack of expression of any of the studied genes. (2) The return of the mRNA gene expression to baseline values in the older rats prior to healing may contribute to their delayed union. (3) No genes were overly up-regulated in the older rats. The slower healing response of the older rats did not stimulate a negative-feedback increase in the mRNA expression of stimulatory cytokines.
doi:10.1186/1471-2474-2-2
PMCID: PMC34552  PMID: 11454240
10.  The relationship of the factor V Leiden mutation or the deletion-deletion polymorphism of the angiotensin converting enzyme to postoperative thromboembolic events following total joint arthroplasty 
Background
Although all patients undergoing total joint arthroplasty are subjected to similar risk factors that predispose to thromboembolism, only a subset of patients develop this complication. The objective of this study was to determine whether a specific genetic profile is associated with a higher risk of developing a postoperative thromboembolic complication. Specifically, we examined if the Factor V Leiden (FVL) mutation or the deletion polymorphism of the angiotensin-converting enzyme (ACE) gene increased a patient's risk for postoperative thromboembolic events. The FVL mutation has been associated with an increased risk of idiopathic thromboembolism and the deletion polymorphism of the ACE gene has been associated with increased vascular tone, attenuated fibrinolysis and increased platelet aggregation.
Methods
The presence of these genetic profiles was determined for 38 patients who had a postoperative symptomatic pulmonary embolus or proximal deep venous thrombosis and 241 control patients without thrombosis using molecular biological techniques.
Results
The Factor V Leiden mutation was present in none of the 38 experimental patients and in 3% or 8 of the 241 controls (p = 0.26). Similarly there was no difference detected in the distribution of polymorphisms for the ACE gene with the deletion-deletion genotype present in 36% or 13 of the 38 experimental patients and in 31% or 74 of the 241 controls (p = 0.32).
Conclusions
Our results suggest that neither of these potentially hypercoaguable states are associated with an increased risk of symptomatic thromboembolic events following total hip or knee arthroplasty in patients receiving pharmacological thromboprophylaxis.
doi:10.1186/1471-2474-2-1
PMCID: PMC32204  PMID: 11311153

Results 1-10 (10)