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1.  IFNγ production in peripheral blood of early Lyme disease patients to hLFAαL (aa326-345) 
Background
It has been proposed that outer surface protein A (OspA) of Borrelia burgdorferi sensu stricto contains a T helper 1 (Th1) cell epitope that could play a role in an autoimmune response to hLFA1.
Methods
We used two peptides, hLFAαL (aa326-345) and Borrelia burgdorferi OspAB31 (aa164-183), as stimulating antigens to measure Th1 proinflammatory IFNγ cytokine production in peripheral blood of Lyme disease patients presenting with EM without history of arthritis, as well as in peripheral blood of healthy individuals.
Results
IFNγ responses to hLFA1 peptide were observed in 11 of 19 Lyme disease patients and in 3 of 15 healthy controls. In contrast, only 2 of 19 of the Lyme disease patients and none of the controls responded to the homologous OspAB31 peptide.
Conclusions
IFNγ was produced in response to stimulation with peptide hLFAαL (aa326-345) in peripheral blood of 58% of patients with early Lyme disease without signs of arthritis, as well as in peripheral blood of 20% of healthy individuals, but not in response to stimulation with the homologous OspAB31 (aa164-183) peptide (p < 0.05). Our results suggest that reactivity to the hLFA1 peptide in peripheral blood may be the result of T cell degeneracy.
doi:10.1186/1471-2474-3-25
PMCID: PMC134469  PMID: 12385648
2.  Appendicular bone mass and knee and hand osteoarthritis in Japanese women: a cross-sectional study 
Background
It has been reported that there is an inverse association between osteoarthritis (OA) and osteoporosis. However, the relationship of bone mass to OA in a Japanese population whose rates of OA are different from Caucasians remains uncertain.
Methods
We studied the association of appendicular bone mineral density (second metacarpal; mBMD) and quantitative bone ultrasound (calcaneus; stiffness index) with knee and hand OA among 567 Japanese community-dwelling women. Knee and hand radiographs were scored for OA using Kellgren-Lawrence (K/L) scales. In addition, we evaluated the presence of osteophytes and of joint space narrowing. The hand joints were examined at the distal and proximal interphalangeal (DIP, PIP) and first metacarpophalangeal/carpometacarpal (MCP/CMC) joints.
Results
After adjusting for age and body mass index (BMI), stiffness index was significantly higher in women with K/L scale, grade 3 at CMC/MCP joint compared with those with no OA. Adjusted means of stiffness index and mBMD were significantly higher in women with definite osteophytes at the CMC/MCP joint compared to those without osteophytes, whereas there were no significant differences for knee, DIP and PIP joints. Stiffness index, but not mBMD, was higher in women with definite joint space narrowing at the CMC/MCP joint compared with those with no joint space narrowing.
Conclusions
Appendicular bone mass was increased with OA at the CMC/MCP joint, especially among women with osteophytes. Our findings suggest that the association of peripheral bone mass with OA for knee, DIP or PIP may be less clearcut in Japanese women than in other populations.
doi:10.1186/1471-2474-3-24
PMCID: PMC130193  PMID: 12370084
3.  Biomechanical evaluation of immediate stability with rectangular versus cylindrical interbody cages in stabilization of the lumbar spine 
Background
Recent cadaver studies show stability against axial rotation with a cylindrical cage is marginally superior to a rectangular cage. The purpose of this biomechanical study in cadaver spine was to evaluate the stability of a new rectangular titanium cage design, which has teeth similar to the threads of cylindrical cages to engage the endplates.
Methods
Ten motion segments (five L2-3, five L4-5) were tested. From each cadaver spine, one motion segment was fixed with a pair of cylindrical cages (BAK, Sulzer Medica) and the other with paired rectangular cages (Rotafix, Corin Spinal). Each specimen was tested in an unconstrained state, after cage introduction and after additional posterior translaminar screw fixation. The range of motion (ROM) in flexion-extension, lateral bending, and rotation was tested in a materials testing machine, with +/- 5 Nm cyclical load over 10 sec per cycle; data from the third cycle was captured for analysis.
Results
ROM in all directions was significantly reduced (p < 0.05) with both types of cages. There was no significant difference in reduction of ROM in flexion-extension (p = 0.6) and rotation (p = 0.92) between the two cage groups, but stability in lateral bending was marginally superior with the rectangular cages (p = 0.11). Additional posterior fixation further reduced the ROM significantly (p < 0.05) in most directions in both cage groups, but did not show any difference between the cage groups.
Conclusions
There was no significant difference in immediate stability in any direction between the threaded cylindrical cage and the new design of the rectangular cage with endplate teeth.
doi:10.1186/1471-2474-3-23
PMCID: PMC130044  PMID: 12363369
4.  The association between iliocostal distance and the number of vertebral and non-vertebral fractures in women and men registered in the Canadian Database For Osteoporosis and Osteopenia (CANDOO) 
Background
The identification of new methods of evaluating patients with osteoporotic fracture should focus on their usefulness in clinical situations such that they are easily measured and applicable to all patients. Thus, the purpose of this study was to examine the association between iliocostal distance and vertebral and non-vertebral fractures in patients seen in a clinical setting.
Methods
Patient data were obtained from the Canadian Database of Osteoporosis and Osteopenia (CANDOO). A total of 549 patients including 508 women and 41 men participated in this cross-sectional study. There were 142 women and 18 men with prevalent vertebral fractures, and 185 women and 21 men with prevalent non-vertebral fractures.
Results
In women multivariable regression analysis showed that iliocostal distance was negatively associated with the number of vertebral fractures (-0.18, CI: -0.27, -0.09; adjusted for bone mineral density at the Ward's triangle, epilepsy, cerebrovascular disease, inflammatory bowel disease, etidronate use, and calcium supplement use) and for the number of non-vertebral fractures (-0.09, CI: -0.15, -0.03; adjusted for bone mineral density at the trochanter, cerebrovascular disease, inflammatory bowel disease, and etidronate use). However, in men, multivariable regression analysis did not demonstrate a significant association between iliocostal distance and the number of vertebral and non-vertebral fractures.
Conclusions
The examination of iliocostal distance may be a useful clinical tool for assessment of the possibility of vertebral fractures. The identification of high-risk patients is important to effectively use the growing number of available osteoporosis therapies.
doi:10.1186/1471-2474-3-22
PMCID: PMC130045  PMID: 12361480
5.  Efficacy and adverse effects of intravenous lignocaine therapy in fibromyalgia syndrome 
Background
To investigate the effects of intravenous lignocaine infusions (IV lignocaine) in fibromyalgia.
Methods
Prospective study of the adverse effects of IV lignocaine in 106 patients with fibromyalgia; retrospective questionnaire study of the efficacy of IV lignocaine in 50 patients with fibromyalgia.
Results
Prospective study: Two major (pulmonary oedema and supraventricular tachycardia) and 42 minor side-effects were reported. None had long-term sequelae. The commonest was hypotension (17 cases). Retrospective study: Pain and a range of psychosocial measures (on single 11-point scales) improved significantly after treatment. There was no effect of the treatment on work status. The average duration of pain relief after the 6-day course of treatment was 11.5 ± 6.5 weeks.
Conclusions
Intravenous lignocaine appears to be both safe and of benefit in improving pain and quality of life for patients with fibromyalgia. This needs to be confirmed in prospective randomised controlled trials.
doi:10.1186/1471-2474-3-21
PMCID: PMC126218  PMID: 12217079
Fibromyalgia; Lidocaine; Intravenous; Adverse Effects; Side-Effects; Benefits; Pain; Psychosocial; Depression; Quality of Life
6.  Systematic assessment of the quality of osteoporosis guidelines 
Background
Numerous agencies have developed clinical practice guidelines for the management of postmenopausal osteoporosis. The study objective was to conduct a systematic assessment of the quality of osteoporosis guidelines produced since 1998.
Methods
Guidelines were identified by searching MEDLINE (1998+), the world wide web, known guideline developer websites, bibliographies of retrieved guidelines, and through consultation with content experts. Each guideline was then assessed by three independent appraisers using the 'Appraisal Instrument for Clinical Guidelines' (version 1) by Cluzeau.
Results
We identified 26 unique guidelines from 1998–2001 and 21 met our inclusion criteria. Of the 21 guidelines reviewed, 8 were developed by medical societies, 6 by national groups, 6 by government agencies, and 1 by an international group. Twelve of the guidelines were published, 7 were organizational reports, and 2 were accessible only from the web. Half or more of the 20 items assessing the rigor of guideline development were met by 15% (median quality score 23%, range 5–80%, (95% CI 16.5, 34.7)), 81% met at least half of the 12 items assessing guideline content and context (median score 58%, range 17–83%, (95% CI 50.8, 65.5)), and none met half or more of the items assessing guideline application (median score 0%, range 0–47%, (95% CI -0.5 to 12.6)). Eight guidelines described the method used to assess the strength of evidence, and in 6 there was an explicit link between recommendations and the supporting evidence. Ten guidelines were judged not suitable for use in practice, 10 were acceptable with modification, and one was acceptable for use without modification.
Conclusion
The methodological quality of current osteoporosis guidelines is low, although their scores for clinical content were higher. Virtually no guidelines covered dissemination issues. Few guidelines were judged as acceptable for use in their current format.
doi:10.1186/1471-2474-3-20
PMCID: PMC126217  PMID: 12174195
7.  Systemic alendronate prevents resorption of necrotic bone during revascularization. A bone chamber study in rats 
Background
Avascular necrosis of bone (osteonecrosis) can cause structural failure and subsequent deformation, leading to joint dysfunction and pain. Structural failure is the result of resorption of necrotic bone during revascularization, before new bone has formed or consolidated enough for loadbearing. Bone resorption can be reduced by bisphosphonates. If resorption of the necrotic bone could be reduced during the revascularization phase until sufficient new bone has formed, it would appear that structural failure could be avoided.
Methods
To test whether resorption of necrotic bone can be prevented, structural grafts were subjected to new bone ingrowth during systemic bisphosphonate treatment in a rat model.
Results
In rats treated with alendronate the necrotic bone was not resorbed, whereas it was almost entirely resorbed in the controls.
Conclusion
Systemic alendronate treatment prevents resorption of necrotic bone during revascularization. In patients with osteonecrosis, bisphosphonates may therefore prevent collapse of the necrotic bone.
doi:10.1186/1471-2474-3-19
PMCID: PMC126216  PMID: 12165099
8.  Correlation of the score for subjective pain with physical disability, clinical and radiographic scores in recent onset rheumatoid arthritis 
Background
To analyse the relationship between subjective pain score and other measures of clinical, radiographic and functional status; in particular Larsen radiographic scores and Health Assessment Questionnaire (HAQ); in patients with severe rheumatoid arthritis (RA) with a disease duration of less than 3 years.
Methods
In this cross sectional study of 105 patients with RA (76 women, 29 men: mean age 50.93; mean disease duration 15.86 months; 71% rheumatoid factor positive) subjective pain was assessed according to the Visual Analog Scale (VAS). Correlation coefficients between pain score and disease activity measures (patients' global assessment of disease by VAS, number of tender and swollen joints, morning stiffness, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] and titre of rheumatoid factor, radiographic evaluations (Larsen-Dale scores for radiographic damage of the small joints of the hands, wrist and feet), disability measures (health assessment questionnaire [HAQ]), and demographic variables were calculated; hierarchical regression analysis was done with subjective pain score as the dependent variable.
Results
The Spearman's correlation coefficient comparing subjective pain and HAQ was 0.421 (p < 0.001), between subjective pain and global assessment of disease and morning stiffness was 0.573 (p < 0.001) and 0.427 (p < 0.001) respectively, and between pain and number of tender and swollen joints 0.037 and 0.050 respectively (p > 0.05). In regression analysis, global assessment of disease by patients explained 32.8% of the variation in pain intensity score, morning stiffness 10.7%, CRP 4.0%, HAQ 3.8% and Larsen-Dale scores explained 2.1%; other variables were not significant in the model.
Conclusions
Pain scores of patients with early severe rheumatoid arthritis are correlated at higher levels with patients' global assessment of disease and with morning stiffness rather than with radiographic or other clinical variables such as number of tender and swollen joints.
doi:10.1186/1471-2474-3-18
PMCID: PMC117789  PMID: 12133169
Rheumatoid arthritis; pain; pain measurement
9.  Long-term experience with implanted intrathecal drug administration systems for failed back syndrome and chronic mechanical low back pain 
Background
Continuous intrathecal drug delivery has been shown in open studies to improve pain and quality of life in those with intractable back pain who have had spinal surgery. There is limited data on long term effects and and even less for patients with mechanical back pain without prior spinal surgery.
Methods
We have investigated spinal drug administration systems for patients with failed back syndrome and chronic mechanical low back pain by patient questionnaire study of the efficacy of this therapy and a case notes review.
Results
36 patients (97% of 37 approached) completed questionnaires, 24 with failed back syndrome and 12 with chronic mechanical low back pain. Recalled pre-treatment levels with current post-treatment levels of pain and a range of quality of life measures (recorded on 11-point numerical rating scales) were compared. Pain improved significantly in both groups (Wilcoxan signed ranks test, p < 0.005). The majority of quality of life measures improved significantly in the failed back syndrome group (Wilcoxan signed ranks test, p < 0.005) although work interruption and the effect of pain on sex life did not change. There was a trend towards improvement in the majority of quality of life measures in the mechanical back pain group but this did not reach statistical significance due to the smaller numbers in this cohort (p > 0.005, Wilcoxan signed ranks test with Bonferroni correction).
Diamorphine was used in all 37 patients, bupivacaine in 32, clonidine in 27 and baclofen in 3. The mean dose of diamorphine increased for the first 2 years but did not change 2–6 years post implant, averaging 4.5 mg/day. Revision surgery was required in 24% of cases, but reduced to 12% in the later years of our experience.
Conclusions
We conclude that spinal drug administration systems appear to be of benefit in alleviating pain in the failed back syndrome and chronic mechanical low back pain but need to be examined prospectively.
doi:10.1186/1471-2474-3-17
PMCID: PMC116675  PMID: 12076357
10.  Recruitment, augmentation and apoptosis of rat osteoclasts in 1,25-(OH)2D3 response to short-term treatment with 1,25-dihydroxyvitamin D3in vivo 
Background
Although much is known about the regulation of osteoclast (OC) formation and activity, little is known about OC senescence. In particular, the fate of of OC seen after 1,25-(OH)2D3 administration in vivo is unclear. There is evidence that the normal fate of OC is to undergo apoptosis (programmed cell death). We have investigated the effect of short-term application of high dose 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on OC apoptosis in an experimental rat model.
Methods
OC recruitment, augmentation and apoptosis was visualised and quantitated by staining histochemically for tartrate resistant acid phosphatase (TRAP), double staining for TRAP/ED1 or TRAP/DAPI, in situ DNA fragmentation end labelling and histomorphometric analysis.
Results
Short-term treatment with high-dose 1,25-(OH)2D3 increased the recruitment of OC precursors in the bone marrow resulting in a short-lived increase in OC numbers. This was rapidly followed by an increase in the number of apoptotic OC and their subsequent removal. The response of OC to 1,25-(OH)2D3 treatment was dose and site dependent; higher doses producing stronger, more rapid responses and the response in the tibiae being consistently stronger and more rapid than in the vertebrae.
Conclusions
This study demonstrates that (1) after recruitment, OC are removed from the resorption site by apoptosis (2) the combined use of TRAP and ED1 can be used to identify OC and their precursors in vivo (3) double staining for TRAP and DAPI or in situ DNA fragmentation end labelling can be used to identify apoptotic OC in vivo.
doi:10.1186/1471-2474-3-16
PMCID: PMC116579  PMID: 12052261
11.  Experimental arthritis induced by a clinical Mycoplasma fermentans isolate 
Background
Mycoplasma fermentans has been associated with rheumatoid arthritis. Recently, it was detected in the joints and blood of patients with rheumatoid arthritis, but it is not clear yet how the bacteria enter the body and reach the joints. The purpose of this study was to determine the ability of M. fermentans to induce experimental arthritis in rabbits following inoculation of the bacteria in the trachea and knee joints.
Methods
P-140 and PG-18 strains were each injected in the knee joints of 14 rabbits in order to evaluate and compare their arthritogenicity. P-140 was also injected in the trachea of 14 rabbits in order to test the ability of the bacteria to reach the joints and induce arthritis.
Results
M. fermentans produced an acute arthritis in rabbits. Joint swelling appeared first in rabbits injected with P-140, which caused a more severe arthritis than PG-18. Both strains were able to migrate to the uninoculated knee joints and they were detected viable in the joints all along the duration of the experiment. Changes in the synovial tissue were more severe by the end of the experiment and characterized by the infiltration of neutrophils and substitution of adipose tissue by connective tissue. Rabbits intracheally injected with P-140 showed induced arthritis and the bacteria could be isolated from lungs, blood, heart, kidney, spleen, brain and joints.
Conclusion
M. fermentans induced arthritis regardless of the inoculation route. These findings may help explain why mycoplasmas are commonly isolated from the joints of rheumatic patients.
doi:10.1186/1471-2474-3-15
PMCID: PMC116578  PMID: 12057023
12.  Carpal alignment in distal radial fractures 
Background
Carpal malalignment following the malunited distal radial fracture is described to develop as an adaptation to realign the hand to the malunion. It worsens gradually after healing of the fracture due to continued loading of the wrist. It is also reported to develop during the immobilization itself rather than after fracture healing. The present work was aimed to study the natural course and the quantitative assessment of such adaptive carpal realignment following distal radial fracture.
Methods
In a prospective study, 118 distal radial fractures treated with different modalities were followed-up with serial radiographs for a year for assessment of various radiological parameters.
Results
Two patterns of carpal malalignment were identified depending upon the effective radio-lunate flexion (ERLF) measured on pre-reduction radiographs. The midcarpal malalignment was seen in 98 radial fractures (83%) with the lunate following the dorsiflexed fracture fragment and a measured ERLF of less than 25°. The second pattern of radio-carpal malalignment showed the fracture fragment to dorsiflex without taking the lunate with a measured ERLF of more than 25°. The scaphoid did not follow the fracture fragment in both the patterns of malalignment.
Conclusion
It is better to assess distal radial fractures for any wrist ligamentous injury on the post-reduction film with the restored radial anatomy than on the pre-reduction film since most carpal malalignments get corrected with the reduction of the fracture. Similar carpal malalignment reappear with the redisplacement of the fracture as seen in pre-reduction radiographs and develops during the immobilization rather than as a later compensatory mechanism for the malunion.
doi:10.1186/1471-2474-3-14
PMCID: PMC116429  PMID: 12052262
13.  Internet hand x-rays: A comparison of joint space narrowing and erosion scores (Sharp/Genant) of plain versus digitized x-rays in rheumatoid arthritis patients 
Background
The objective of the study is to examine the reliability of erosion and joint space narrowing scores derived from hand x-rays posted on the Internet compared to scores derived from original plain x-rays.
Methods
Left and right x-rays of the hands of 36 patients were first digitized and then posted in standard fashion to a secure Internet website. Both the plain and Internet x-rays were scored for erosions and joint space narrowing using the Sharp/Genant method. All scoring was completed in a blind and randomized manner. Agreement between plain and Internet x-ray scores was calculated using Lin's concordance correlations and Bland-Altman graphical representation.
Results
Erosion scores for plain x-rays showed almost perfect concordance with x-rays read on the Internet (concordance 0.887). However, joint space narrowing scores were only "fair" (concordance 0.365). Global scores demonstrated substantial concordance between plain and Internet readings (concordance 0.769). Hand x-rays with less disease involvement showed a tendency to be scored higher on the Internet versions than those with greater disease involvement. This was primarily evident in the joint space narrowing scores.
Conclusions
The Internet represents a valid medium for displaying and scoring hand x-rays of patients with RA. Higher scores from the Internet version may be related to better viewing conditions on the computer screen relative to the plain x-ray viewing, which did not include magnifying lens or bright light. The capability to view high quality x-rays on the Internet has the potential to facilitate information sharing, education, and encourage collaborative studies.
doi:10.1186/1471-2474-3-13
PMCID: PMC113251  PMID: 11980582
14.  Factors explaining variance in perceived pain in women with fibromyalgia 
Background
We hypothesized that a substantial proportion of the subjectively experienced variance in pain in fibromyalgia patients would be explained by psychological factors alone, but that a combined model, including neuroendocrine and autonomic factors, would give the most parsimonious explanation of variance in pain.
Methods
Psychometric assessment included McGill Pain Questionnaire, General Health Questionnaire, Hospital Anxiety and Depression Rating Scale, Eysenck personality Inventory, Neuroticism and Lie subscales, Toronto Alexithymia Scale, and Multidimensional Health Locus of Control Scale and was performed in 42 female patients with fibromyalgia and 48 female age matched random sample population controls. A subgroup of the original sample (22 fibromyalgia patients and 13 controls) underwent a pharmacological challenge test with buspirone to assess autonomic and adrenocortical reactivity to serotonergic challenge.
Results
Although fibromyalgia patients scored high on neuroticism, anxiety, depression and general distress, only a minor part of variance in pain was explained by psychological factors alone. High pain score was associated with high neuroticism, low baseline cortisol level and small drop in systolic blood pressure after buspirone challenge test. This model explained 41.5% of total pain in fibromyalgia patients. In population controls, psychological factors alone were significant predictors for variance in pain.
Conclusion
Fibromyalgia patients may have reduced reactivity in the central sympathetic system or perturbations in the sympathetic-parasympathetic balance. This study shows that a biopsychosocial model, including psychological factors as well as factors related to perturbations of the autonomic nervous system and hypothalamic-pituitary-adrenal axis, is needed to explain perceived pain in fibromyalgia patients.
doi:10.1186/1471-2474-3-12
PMCID: PMC113754  PMID: 12019032
15.  The impact of incident vertebral and non-vertebral fractures on health related quality of life in postmenopausal women 
Background
Little empirical research has examined the multiple consequences of osteoporosis on quality of life.
Methods
Health related quality of life (HRQL) was examined in relationship to incident fractures in 2009 postmenopausal women 50 years and older who were seen in consultation at our tertiary care, university teaching hospital-affiliated office and who were registered in the Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients. Patients were divided into three study groups according to incident fracture status: vertebral fractures, non-vertebral fractures and no fractures. Baseline assessments of anthropometric data, medical history, therapeutic drug use, and prevalent fracture status were obtained from all participants. The disease-targeted mini-Osteoporosis Quality of Life Questionnaire (mini-OQLQ) was used to measure HRQL.
Results
Multiple regression analyses revealed that subjects who had experienced an incident vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.86; 95% confidence intervals (CI): -1.30, -0.43) and the symptoms (-0.76; 95% CI: -1.23, -0.30), physical functioning (-1.12; 95% CI: -1.57, -0.67), emotional functioning (-1.06; 95% CI: -1.44, -0.68), activities of daily living (-1.47; 95% CI: -1.97, -0.96), and leisure (-0.92; 95% CI: -1.37, -0.47) domains of the mini-OQLQ. Patients who experienced an incident non-vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.47; 95% CI: -0.70, -0.25), and the symptoms (-0.25; 95% CI: -0.49, -0.01), physical functioning (-0.39; 95% CI: -0.65, -0.14), emotional functioning (-0.97; 95% CI: -1.20, -0.75) and the activities of daily living (-0.47; 95% CI: -0.73, -0.21) domains.
Conclusion
Quality of life decreased in patients who sustained incident vertebral and non-vertebral fractures.
doi:10.1186/1471-2474-3-11
PMCID: PMC107028  PMID: 11967146
16.  Adolescent standing postural response to backpack loads: a randomised controlled experimental study 
Background
Backpack loads produce changes in standing posture when compared with unloaded posture. Although 'poor' unloaded standing posture has been related to spinal pain, there is little evidence of whether, and how much, exposure to posterior load produces injurious effects on spinal tissue. The objective of this study was to describe the effect on adolescent sagittal plane standing posture of different loads and positions of a common design of school backpack. The underlying study aim was to test the appropriateness of two adult 'rules-of-thumb'-that for postural efficiency, backpacks should be worn high on the spine, and loads should be limited to 10% of body weight.
Method
A randomised controlled experimental study was conducted on 250 adolescents (12–18 years), randomly selected from five South Australian metropolitan high schools. Sagittal view anatomical points were marked on head, neck, shoulder, hip, thigh, knee and ankle. There were nine experimental conditions: combinations of backpack loads (3, 5 or 10% of body weight) and positions (backpack centred at T7, T12 or L3). Sagittal plane photographs were taken of unloaded standing posture (baseline), and standing posture under the experimental conditions. Posture was quantified from the x (horizontal) coordinate of each anatomical point under each experimental condition. Differences in postural response were described, and differences between conditions were determined using Analysis of Variance models.
Results
Neither age nor gender was a significant factor when comparing postural response to backpack loads or conditions. Backpacks positioned at T7 produced the largest forward (horizontal) displacement at all the anatomical points. The horizontal position of all anatomical points increased linearly with load.
Conclusion
There is evidence refuting the 'rule-of-thumb' to carry the backpack high on the back. Typical school backpacks should be positioned with the centre at waist or hip level. There is no evidence for the 10% body weight limit.
doi:10.1186/1471-2474-3-10
PMCID: PMC111061  PMID: 11960561
17.  Observations on morphologic changes in the aging and degenerating human disc: Secondary collagen alterations 
Background
In the annulus, collagen fibers that make up the lamellae have a wavy, planar crimped pattern. This crimping plays a role in disc biomechanical function by allowing collagen fibers to stretch during compression. The relationship between morphologic changes in the aging/degenerating disc and collagen crimping have not been explored.
Methods
Ultrastructural studies were performed on annulus tissue from 29 control (normal) donors (aged newborn to 79 years) and surgical specimens from 49 patients (aged 16 to 77 years). Light microscopy and specialized image analysis to visualize crimping was performed on additional control and surgical specimens. Human intervertebral disc tissue from the annulus was obtained in a prospective morphologic study of the annulus. Studies were approved by the authors' Human Subjects Institutional Review Board.
Results
Three types of morphologic changes were found to alter the crimping morphology of collagen: 1) encircling layers of unusual matrix disrupted the lamellar collagen architecture; 2) collagen fibers were reduced in amount, and 3) collagen was absent in regions with focal matrix loss.
Conclusions
Although proteoglycan loss is well recognized as playing a role in the decreased shock absorber function of the aging/degenerating disc, collagen changes have received little attention. This study suggests that important stretch responses of collagen made possible by collagen crimping may be markedly altered by morphologic changes during aging/degeneration and may contribute to the early tissue changes involved in annular tears.
doi:10.1186/1471-2474-3-9
PMCID: PMC101374  PMID: 11914152
18.  Morphological, histochemical, and interstitial pressure changes in the tibialis anterior muscle before and after aortofemoral bypass in patients with peripheral arterial occlusive disease 
Background
Morphological and electrophysiological studies of ischemic muscles in peripheral arterial disease disclosed evidence of denervation and fibre atrophy. The purpose of the present study is to describe morphological changes in ischemic muscles before and after reperfusion surgery in patients with peripheral occlusive arterial disease, and to provide an insight into the effect of reperfusion on the histochemistry of the reperfused muscle.
Methods
Muscle biopsies were obtained from the tibialis anterior of 9 patients with chronic peripheral arterial occlusive disease of the lower extremities, before and after aortofemoral bypass, in order to evaluate the extent and type of muscle fibre changes during ischemia and after revascularization. Fibre type content and muscle fibre areas were quantified using standard histological and histochemical methods and morphometric analysis. Each patient underwent concentric needle electromyography, nerve conduction velocity studies, and interstitial pressure measurements.
Results
Preoperatively all patients showed muscle fibre atrophy of both types, type II fibre area being more affected. The mean fibre cross sectional area of type I was 3,745 μm2 and of type II 4,654 μm2 . Fibre-type grouping, great variation in fibre size and angular fibres were indicative of chronic dennervation-reinnervation, in the absence of any clinical evidence of a neuropathic process. Seven days after the reperfusion the areas of both fibre types were even more reduced, being 3,086 μm2 for type I and 4,009 μm2 for type II, the proportion of type I fibres, and the interstitial pressure of tibialis anterior were increased.
Conclusions
The findings suggest that chronic ischemia of the leg muscles causes compensatory histochemical changes in muscle fibres resulting from muscle hypoxia, and chronic dennervation-reinnervation changes, resulting possibly from ischemic neuropathy. Reperfusion seems to bring the oxidative capacity of the previously ischemic muscle closer to normal.
doi:10.1186/1471-2474-3-8
PMCID: PMC89010  PMID: 11895571
19.  Effect of simvastatin on bone markers in osteopenic women: a placebo-controlled, dose-ranging trial [ISRCTN85429598] 
Background
Hydroxymethylglutaryl coenzyme A reductase inhibitors increase new bone formation in vitro and in rodents. Results of epidemiologic analyses evaluating the association between use of these cholesterol-lowering drugs, bone mineral density and fracture have been mixed.
Methods
Women (n = 24) with osteopenia, assessed by broad band ultrasound attenuation, were randomized to simvastatin 20 mg, 40 mg or identical-appearing placebo for 12 weeks. Fasting lipid profiles and biochemical markers of bone formation (bone-specific alkaline phosphatase) and resorption (N-telopeptides and C-terminal propeptide of type 1 collagen) were measured at baseline, 6 and 12 weeks.
Results
Plasma low density lipoprotein-cholesterol concentration fell 7%, 39% (p < 0.01 vs baseline) and 47% (p < 0.01 vs baseline) after 12 weeks of treatment with placebo, simvastatin 20 mg and 40 mg, respectively. At baseline, bone marker concentrations were similar in the three treatment groups. At 6 and 12 weeks, bone marker concentrations were not different from baseline, and no significant differences in bone marker concentrations were observed between treatment groups at either 6 or 12 weeks.
Conclusion
Among osteopenic women, treatment with simvastatin for 12 weeks did not affect markers of bone formation or resorption.
doi:10.1186/1471-2474-3-7
PMCID: PMC79000  PMID: 11879528
20.  Effect of vitamin D on bone mineral density of elderly patients with osteoporosis responding poorly to bisphosphonates 
Background
Bisphosphonates are indicated in the prevention and treatment of osteoporosis. However, bone mineral density (BMD) continues to decline in up to 15% of bisphosphonate users. While randomized trials have evaluated the efficacy of concurrent bisphosphonates and vitamin D, the incremental benefit of vitamin D remains uncertain.
Methods
Using data from the Canadian Database of Osteoporosis and Osteopenia (CANDOO), we performed a 2-year observational cohort study. At baseline, all patients were prescribed a bisphosphonate and counseled on vitamin D supplementation. After one year, patients were divided into two groups based on their response to bisphosphonate treatment. Non-responders were prescribed vitamin D 1000 IU daily. Responders continued to receive counseling on vitamin D.
Results
Of 449 patients identified, 159 were non-responders to bisphosphonates. 94% of patients were women. The mean age of the entire cohort was 74.6 years (standard deviation = 5.6 years). In the cohort of non-responders, BMD at the lumbar spine increased 2.19% (p < 0.001) the year after vitamin D was prescribed compared to a decrease of 0.55% (p = 0.36) the year before. In the cohort of responders, lumbar spine BMD improved 1.45% (p = 0.014) the first year and 1.11% (p = 0.60) the second year. The difference between the two groups was statistically significant the first year (p < 0.001) but not the second (p = 0.60). Similar results were observed at the femoral neck but were not statistically significant.
Conclusion
In elderly patients with osteoporosis not responding to bisphosphonates, vitamin D 1000 IU daily may improve BMD at the lumbar spine.
doi:10.1186/1471-2474-3-6
PMCID: PMC65678  PMID: 11860614
21.  Ligamentous rupture of the ACL associated with dislocated fracture of the proximal tibial physis in a 12-year-old boy 
Background
Dislocated fracture of the proximal physeal plate of the tibia with or without metaphyseal fragment is rare in children. This unusual fracture classically excludes rupture of the anterior cruciate ligament due to the ligament's stability. A combination of both injuries has not been previously published in the literature.
Case presentation
The authors report the case of a 12-year-old boy who presented with a dislocated fracture (Salter-Harris II) of the proximal tibia combined with ligamentous rupture of the anterior cruciate ligament after a sporting accident.
doi:10.1186/1471-2474-3-5
PMCID: PMC78999  PMID: 11876825
22.  Modeling of failure mode in knee ligaments depending on the strain rate 
Background
The failure mechanism of the knee ligament (bone-ligament-bone complex) at different strain rates is an important subject in the biomechanics of the knee. This study reviews and summarizes the literature describing ligament injury as a function of stain rate, which has been published during the last 30 years.
Methods
Three modes of injury are presented as a function of strain rate, and they are used to analyze the published cases. The number of avulsions is larger than that of ligament tearing in mode I. There is no significant difference between the number of avulsions and ligament tearing in mode II. Ligament tearing happens more frequently than avulsion in mode III.
Results
When the strain rate increases, the order of mode is mode I, II, III, I, and II. Analytical models of ligament behavior as a function of strain rate are also presented and used to provide an integrated framework for describing all of the failure regimes. In addition, this study showed the failure mechanisms with different specimens, ages, and strain rates.
Conclusion
There have been several a numbers of studies of ligament failure under various conditions including widely varying strain rates. One issue in these studies is whether ligament failure occurs mid-ligament or at the bone attachment point, with assertions that this is a function of the strain rate. However, over the range of strain rates and other conditions reported, there has appeared to be discrepancies in the conclusions on the effect of strain rate. The analysis and model presented here provides a unifying assessment of the previous disparities, emphasizing the differential effect of strain rate on the relative strengths of the ligament and the attachment.
doi:10.1186/1471-2474-3-3
PMCID: PMC65677  PMID: 11860613
23.  Expression and localization of estrogen receptor-β in annulus cells of the human intervertebral disc and the mitogenic effect of 17-β-estradiol in vitro 
Background
Recent evidence suggests that estrogens exert effects in different tissues throughout the body, and that the estrogen receptor β (ERβ) may be important for the action of estrogen (17-β-estradiol) on the skeleton. The cellular localization of ERβ in the human intervertebral disc, however, has not yet been explored.
Methods
Human disc tissue and cultured human disc cells were used for immunocytochemical localization of ERβ. mRNA was isolated from cultured human disc cells, and RT-PCR amplification of ERβ was employed to document molecular expression of this receptor. Cultured human disc cells were tested to determine if 17-β-estradiol stimulated cell proliferation.
Results
In this report data are presented which provide evidence for ERβ gene expression in human intervertebral disc cells in vivo and in vitro. Culture of annulus cells in the presence of 10-7 M 17-β-estradiol significantly increased cell proliferation.
Conclusions
These data provide new insight into the biology of cells in the annulus of the intervertebral disc.
doi:10.1186/1471-2474-3-4
PMCID: PMC65546  PMID: 11846890
24.  Norepinephrine-evoked pain in fibromyalgia. A randomized pilot study [ISRCTN70707830] 
Background
Fibromyalgia syndrome displays sympathetically maintained pain features such as frequent post-traumatic onset and stimuli-independent pain accompanied by allodynia and paresthesias. Heart rate variability studies showed that fibromyalgia patients have changes consistent with ongoing sympathetic hyperactivity. Norepinephrine-evoked pain test is used to assess sympathetically maintained pain syndromes. Our objective was to define if fibromyalgia patients have norepinephrine-evoked pain.
Methods
Prospective double blind controlled study. Participants: Twenty FM patients, and two age/sex matched control groups; 20 rheumatoid arthritis patients and 20 healthy controls. Ten micrograms of norepinephrine diluted in 0.1 ml of saline solution were injected in a forearm. The contrasting substance, 0.1 ml of saline solution alone, was injected in the opposite forearm. Maximum local pain elicited during the 5 minutes post-injection was graded on a visual analog scale (VAS). Norepinephrine-evoked pain was diagnosed when norepinephrine injection induced greater pain than placebo injection. Intensity of norepinephrine-evoked pain was calculated as the difference between norepinephrine minus placebo-induced VAS scores.
Results
Norepinephrine-evoked pain was seen in 80 % of FM patients (95% confidence intervals 56.3 – 94.3%), in 30 % of rheumatoid arthritis patients and in 30 % of healthy controls (95% confidence intervals 11.9 – 54.3) (p < 0.05). Intensity of norepinephrine-evoked pain was greater in FM patients (mean ± SD 2.5 ± 2.5) when compared to rheumatoid arthritis patients (0.3 ± 0.7), and healthy controls (0.3 ± 0.8) p < 0.0001.
Conclusions
Fibromyalgia patients have norepinephrine-evoked pain. This finding supports the hypothesis that fibromyalgia may be a sympathetically maintained pain syndrome.
doi:10.1186/1471-2474-3-2
PMCID: PMC65524  PMID: 11860612
25.  Open antero-lateral dislocation of the elbow. A case report 
Background
Open dislocations are infrequent, often associated with damage to the neuro vascular structures. We present an unusual case of an open antero-lateral dislocation of the elbow, which was not associated with any vascular or neural injury.
Case presentation
A 34 year female dance instructor sustained an open dislocation of her elbow. Surgical exploration was undertaken. No major neurovascular injury was present. There was almost complete disruption of all the muscular and ligamentous attachments to the distal humerus and the proximal radius and ulna, which were not formally repaired during surgery. The elbow was found to be very unstable, and was placed in a back slab. The functional recovery was complete in about six months, the patient regaining full range of elbow movement. Elbow dislocations without associate fractures are adequately treated by manipulation and reduction, in spite of the almost complete disruption of the soft tissues around the joint.
doi:10.1186/1471-2474-3-1
PMCID: PMC64646  PMID: 11806760

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