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Biomedical subjects

Guy Trudel

Publications and source records attributed to Guy Trudel.

At least 19 recordsLinked to original sources

Genetic influences on joint contractures secondary to immobilization.

The primary research question of this study queries whether, beyond environmental conditions, genetic factors affect the development of joint contractures. We hypothesized that intrinsic genetic factors influence the severity of joint contractures developing secondary to joint immobilization. Forty rats from four inbred rat strains had one leg immobilized in knee flexion for 4 weeks. The contracture was measured mechanically as the lack of range of motion to a standardized torque. Using the contralateral leg as a control, the average severity of the contracture could be calculated and compared between strains. All immobilized legs presented knee contractures after 4 weeks of immobilization. Two strains (Dark Agouti and Fisher 344) showed a larger mean knee contracture than those of the two other rat strains (Augustus Copenhagen Irish and Brown Norway). Environmental factors, such as immobility, are usually identified as a cause of a joint contracture. These results demonstrate that, in addition to mechanical factors in the environment of a joint, intrinsic genetic factors participate in the process leading to joint contracture. This demonstration has important consequences for directing future research and may lead to interventions to help patients at risk of developing joint contractures.

Animals↗

Space flight rehabilitation.

The weightless environment of space imposes specific physiologic adaptations on healthy astronauts. On return to Earth, these adaptations manifest as physical impairments that necessitate a period of rehabilitation. Physiologic changes result from unloading in microgravity and highly correlate with those seen in relatively immobile terrestrial patient populations such as spinal cord, geriatric, or deconditioned bed-rest patients. Major postflight impairments requiring rehabilitation intervention include orthostatic intolerance, bone demineralization, muscular atrophy, and neurovestibular symptoms. Space agencies are preparing for extended-duration missions, including colonization of the moon and interplanetary exploration of Mars. These longer-duration flights will result in more severe and more prolonged disability, potentially beyond the point of safe return to Earth. This paper will review and discuss existing space rehabilitation plans for major postflight impairments. Evidence-based rehabilitation interventions are imperative not only to facilitate return to Earth but also to extend the safe duration of exposure to a physiologically hostile microgravity environment.

Adaptation, Physiological↗

Delay of supraspinatus repair by up to 12 weeks does not impair enthesis formation: a quantitative histologic study in rabbits.

The purpose of this study was to find out whether supraspinatus repair delayed by up to12 weeks affects the formation of a new enthesis when compared to an immediate repair. In 67 rabbits, the supraspinatus fibrocartilaginous enthesis of one shoulder was resected. The tendon was attached to the greater tuberosity either immediately, after a 6-week, or after a 12-week delay. Five histologic variables were used to assess enthesis formation: number of non-chondrocytes, number of chondrocytes, alignment of chondrocytes in rows, area of metachromasia on toluidine blue (TB)-stained sections indicating proteoglycan content, and area of diffracted polarized light indicating spatial alignment of collagen fibers. For every variable, progressive enthesis formation was observed. Again, for every variable and at every time point studied, no statistically significant difference was observed between tendons repaired immediately, after 6, or after 12 weeks (all p>0.05). Supraspinatus tendon repairs delayed by 6 and 12 weeks constituted an enthesis which proceeded identically to one immediately repaired. Formation of a fibrocartilaginous enthesis depended on the elapsed time after repair and not on the duration between detachment and repair. Despite stated limitations, these results support both a trial of conservative treatment after a rotator cuff tear and a positive outcome of rotator cuff repair even if delayed by up to 12 weeks.

Animals↗

Comparative anatomy of rabbit and human achilles tendons with magnetic resonance and ultrasound imaging.

We sought to describe the comparative anatomy of the Achilles tendon in rabbits and humans by using macroscopic observation, magnetic resonance imaging, and ultrasonography. The calcaneus-Achilles tendon-gastrocnemius-soleus complexes from 18 New Zealand white rabbits underwent ultrasound (US) and magnetic resonance (MR) imaging and gross anatomic sectioning; these results were compared with those from a cadaveric gastrocnemius-soleus-Achilles tendon-calcaneus specimen from a 68-y-old human male. The medial and lateral gastrocnemius muscle tendons merged 5.2 +/- 0.6 mm proximal to the calcaneal insertion macroscopically, at 93% of their course, different from the gastrocnemius human tendons, which merged at 23% of their overall course. The rabbit flexor digitorum superficialis tendon, corresponding to the flexor digitorum longus tendon in human and comparable in size with the gastrocnemius tendons, was located medial and anterior to the medial gastrocnemius tendon proximally and rotated dorsally and laterally to run posterior to the Achilles tendon-calcaneus insertion. In humans, the flexor digitorum longus tendon tracks posteriorly to the medial malleolus. The soleus muscle and tendon are negligible in the rabbit; these particular comparative anatomic features in the rabbit were confirmed on the MR images. Therefore the rabbit Achilles tendon shows distinctive gross anatomical and MR imaging features that must be considered when using the rabbit as a research model, especially for mechanical testing, or when generalizing results from rabbits to humans.

Achilles Tendon↗

Thawing of frozen calcaneus bone specimens has no effect on the bone mineral density using dual energy x-ray absorptiometry: a study in rabbits and humans.

The purpose of this paper is to study whether the deep freezing of bone and later thawing affects the bone mineral density (BMD) measurement. We used 56 calcanei from 28 adult female New Zealand white rabbits and 102 human calcanei from 51 donors post-mortem (27 men and 24 women, age 30-89). Dual energy x-ray absorptiometry evaluated BMD of the frozen specimen and of the thawed specimen. A main analysis compared BMD of each specimen in the frozen and thawed states. The mean BMD of 224 areas of frozen rabbits' calcanei was 0.31 +/- 0.08 g cm(-2) (95% confidence interval (CI) from 0.30 to 0.32 g cm(-2)) while the mean BMD of thawed rabbits' calcanei was 0.31 +/- 0.08 g cm(-2) (95% CI from 0.30 to 0.32 g cm(-2); paired t-test p > 0.01). The mean BMD of 306 areas of frozen human calcaneus was 0.73 +/- 0.22 g cm(-2) (95% CI from 0.70 to 0.76 g cm(-2)) while the mean BMD of thawed human calcaneus was 0.73 +/- 0.22 g cm(-2) (95% CI from 0.70 to 0.76 g cm(-2); p > 0.01). For both the rabbit and the human calcanei, a Bland-Altman analysis showed a mean difference between the BMD in the frozen and thawed states of 0.00 (limits of agreement, rabbit: -0.07 to 0.08 g cm(-2), human: -0.16 to 0.21 g cm(-2)). A high correlation was observed between calcaneus BMD in the frozen and thawed states (r = 0.94, 0.97, 0.92 and 0.99 respectively in all rabbit calcanei, all human calcanei, immobilized rabbit calcanei and osteopenic human calcanei, all p < 0.01). Bone mineral density is not affected by deep freezing and later thawing of the specimen. Therefore, the specimens need not be thawed to obtain valid and precise BMD measurement. These results are relevant to general musculoskeletal as well as osteoporosis research where the specimens undergo multiple tests in series.

Absorptiometry, Photon↗

Contrasting alterations of apposed and unapposed articular cartilage during joint contracture formation.

OBJECTIVE: To quantify histologic articular cartilage alterations after immobilization, distinguishing between apposed and unapposed sites in an animal model of joint contracture. DESIGN: Experimental controlled trial. SETTING: Laboratory, in vivo study. ANIMALS: Adult male Sprague-Dawley rats (N=128). INTERVENTIONS: One hundred seventeen animals had 1 knee internally immobilized or sham-operated for 2, 4, 8, 16, or 32 weeks. One knee in 11 nonoperated animals served as controls. Main outcome measures On standardized sections, we identified femur and tibia cartilage sites that were apposed or that were unapposed. We quantified 4 characteristics: number of chondrocytes in the superficial and deep cartilage; matrix staining intensity to toluidine blue; surface irregularity of articular cartilage; and thickness of cartilage. RESULTS: Immobilized knees harbored fewer chondrocytes in the superficial cartilage at apposed sites and in the deep cartilage at unapposed sites. Matrix staining decreased only at unapposed sites. Cartilage surface became significantly more irregular at both sites but cartilage thickness remained unchanged. Noncartilaginous tissues appeared only at unapposed sites in the superficial and deep cartilage. CONCLUSIONS: Immobilization led to contrasting patterns of cartilage degeneration at apposed sites compared with unapposed sites. These results suggest distinct pathogenetic pathways for cartilage alterations, possibly through absence of mechanical forces (negative mechanotransduction) at unapposed sites and cyclic pressure at apposed sites. Considering the limited potential for cartilage self-repair, these results support the need for early diagnosis and aggressive mobilization of joints that are developing contractures.

Animals↗

Formation of a new enthesis after attachment of the supraspinatus tendon: A quantitative histologic study in rabbits.

PURPOSE: To quantify in a longitudinal study non-chondrocytic cells and chondrocytes, tissular architecture as well as extracellular matrix restoration during the formation of an enthesis following supraspinatus tendon attachment to the humerus. METHODS: In 89 rabbits, one supraspinatus fibrocartilaginous enthesis was resected and the tendon either attached to the greater tuberosity (n=75) or not attached (n=14). The animals were sacrificed after 2, 6, 8, 12 or 24 weeks. The operated and contralateral shoulders were processed for histologic sections. Number of non-chondrocytes, chondrocytes and alignment of chondrocytes in rows were assessed histologically. Extracellular matrix restoration was measured based on (1) area of toluidine blue metachromasia indicating proteoglycan content and (2) on area of diffracted polarized light indicating spatial collagen fiber alignment. RESULTS: In the attached tendon, the number of non-chondrocytic cells sharply increased at 2 weeks, progressively decreased thereafter but remained higher than controls at all time points. Chondrocytes appeared at 2 weeks and their number reached control levels by 6 weeks (136+/-14 vs 144+/-15 controls, p>.05). The percentage of chondrocytes aligned in rows increased from 19+/-4% at 2 weeks to reach near normal values at 24 weeks (71+/-3% vs 78+/-2% controls, p>.05). Area of metachromasia increased from 0.1+/-0.1 mm(2) at 2 weeks to 3.8+/-0.3 mm(2) at 24 weeks, still below contralateral enthesis levels (4.6+/-0.1 mm(2), p<.05). Area of diffracted polarized light enlarged from 12+/-2 x 10(3) microm(2) at 2 weeks to 151+/-19 x 10(3) microm(2) at 24 weeks, still significantly smaller than contralateral levels (177+/-13 x 10(3) microm(2), p<.05). Neither chondrocytes nor metachromasia were observed in the non-attached tendons. CONCLUSION: A new enthesis was formed after attachment of the supraspinatus tendon into bony trough. Histomorphometry allowed to document extensive non-chondrocytic proliferation that was followed by appearance of chondrocytes and their spatial organization, a process was complete by 24 weeks. Extracellular matrix formation as well as spatial alignment of collagen fibers were delayed and not complete by 24 weeks. This first longitudinal investigation on the formation of the supraspinatus enthesis using quantitative outcome measures cautions against too early and too aggressive a rehabilitation program.

Animals↗

Dual cryogenic fixation for mechanical testing of soft musculoskeletal tissues.

Mechanical testing of soft musculoskeletal structures like tendons and ligaments are essential to medical advances. A long-standing limitation for testing these structures in isolation has been the ability to solidly fix both ends of the tendon. Cryogenic fixation technology was leveraged into the development of a dual cryogenic fixation (DCF) device. Results of the study show that the DCF allows tendons to be tested in isolation, at physiologic temperatures, with excellent reproducibility.

Animals↗

Prothrombin gene expression in articular cartilage with a putative role in cartilage degeneration secondary to joint immobility.

OBJECTIVE: To test the hypothesis that thrombin is expressed by chondrocytes from human and animal articular cartilage and to monitor its levels of expression during cartilage degeneration induced by joint immobility in a rat model. METHODS: Rat knees were immobilized for periods of 2 or 4 weeks, after which the articular cartilage was harvested, total RNA extracted, and the differential display (ddPCR) protocol applied to identify differentially expressed genes. One differentially expressed fragment showed 100% homology with the prothrombin gene. Results were verified by RT-PCR, Northern and Western blot analysis, and immunohistochemistry in human, rat, and rabbit articular cartilage. RESULTS: In our rat model of cartilage degeneration induced by joint immobilization, increases in the levels of prothrombin mRNA, thrombin protein, and fibrin deposition were observed. Expression of the prothrombin gene by chondrocytes was confirmed by ddPCR (rat), RT-PCR (rat and human), and by Northern blot analysis (rabbit). In addition, thrombin-like immunoreactivity was increased in chondrocytes after a 4 week immobilization period compared with rat knees receiving sham surgery. Thrombin activity was reflected by the presence of fibrin immunoreactivity in operated rat knee joints. CONCLUSION: Articular chondrocytes express the prothrombin gene and its local expression in joints is translated into thrombin protein. Prothrombin expression is increased in response to joint immobility. Our results support generation of thrombin locally in joints and an upregulation of thrombin expression in cartilage degeneration secondary to immobility. These results may provide information on the source of increased thrombin activity in various animal models and in clinical forms of arthritis.

Animals↗

Relevance of pathology and basic research to the surgeon treating rotator cuff disease.

For any physician expecting a successful outcome of a treatment regimen a thorough understanding of the underlying pathogenetic mechanism and the pathology of the disease process is an absolute prerequisite. In addition, the surgeon, obviously wishing to obtain a positive outcome of the procedure, must know the reaction of the body to his or her surgical actions. In particular, he or she must be familiar with the factors guaranteeing an uneventful healing process. For example, with rotator cuff disease it is important to realize that the site of degeneration leading eventually to tearing does not lie in the tendon itself but at its insertion into bone. Moreover, the cells and vessels needed for healing after surgical repair do not originate from the torn tendinous stumps. An important source of cells and vessels is the subacromial bursa overlying the site of tearing. Consequently, the bursa must be preserved at all cost. The subchondral bone trough into which the medial tendon stump is usually anchored during repair represents the other source of healing tissue. Whereas surgeons understandably concentrate their attention on the site of tearing, the fate of the muscle in the torn bone-tendon-muscle unit must not be neglected. In experimental studies we were able to measure muscle atrophy and fat accumulation and could quantify their evolution over time. Finding no reversal of these two parameters after successful repair was disturbing. Shoulder surgeons will benefit from this comprehensive review of updated concepts.

Animals↗

Mechanical effects of immobilization on the Achilles' tendon.

OBJECTIVE: To measure the biomechanical effects of immobilization on the Achilles' tendon. DESIGN: Experimental, controlled study. SETTING: Physiatry research laboratory. ANIMALS: Twenty adult rabbits. INTERVENTION: One hindlimb immobilized in a cast for 4 weeks (n=10) or 8 weeks (n=10). The contralateral legs (n=20) served as controls. MAIN OUTCOME MEASURES: Cross-sectional Achilles' tendon area, mode of failure, mean failure load, and tendon stiffness. RESULTS: The Achilles' tendon cross-sectional area did not change. Achilles' tendon-calcaneus units failed at insertion at 4 weeks and in controls. Calcaneus fracture was the most prevalent mode of failure at 8 weeks. The mean load to failure of both immobilized groups (4wk: 187.5+/-45.7N; 8wk: 162.6+/-39.3N) was significantly smaller than that of the control group (549.2+/-93.7N, both P<.005). The mean tendon stiffness of both immobilized groups (4wk: 64.6+/-24.8N/mm; 8wk: 53.9+/-19.9N/mm) was significantly lower than that of the control group (125.1+/-26.5N/mm, both P<.005). CONCLUSIONS: Immobility for up to 8 weeks caused decreased stiffness but no atrophy or rupture of the Achilles' tendon, suggesting that immobility does not constitute a risk factor for Achilles' tendon midsubstance rupture. Clinically, graded reloading is required after immobilization to restore the tendon insertion and to reverse calcaneal disuse osteoporosis.

Achilles Tendon↗

Localized and adaptive synoviocyte proliferation characteristics in rat knee joint contractures secondary to immobility.

OBJECTIVE: To investigate the proliferative activity of synoviocytes in joint contracture. DESIGN: Experimental controlled trial. SETTING: Laboratory in vivo study. ANIMALS: Adult male Sprague-Dawley rats (avg weight, 340g). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We immobilized the knee joints of 24 rats, in 135 degrees of flexion, for up to 32 weeks. Controls were 24 sham-operated and 5 unoperated rats. On sagittal sections, synoviocytes that stained with a proliferating cell nuclear antigen antibody were counted over the anterior and posterior synovial intima. The length of the synovial intima was also measured. RESULTS: The absolute number of proliferating synoviocytes decreased markedly in the posterior capsule of knee joints immobilized for more than 2 weeks (2.4+/-1.0 vs 22.7+/-7.1 at week 16, P<.05), and so did the synovial intima length (1.4+/-0.1mm vs 8.6+/-0.5mm at week 16, P<.05). No change occurred anteriorly. CONCLUSION: A decreased number of proliferating synoviocytes and increased intima adhesion in the posterior capsule characterized joint contractures. The data further suggest that the synovial intima adapted to the new position of the joint. Phenomena of mechanotransduction could explain the fact that adaptations were restricted to the posterior synovial intima.

Animals↗

Early reattachment does not reverse atrophy and fat accumulation of the supraspinatus--an experimental study in rabbits.

INTRODUCTION: Reattachment of the supraspinatus (SSP) tendon after spontaneous rupture leads to improved shoulder function. Whether this improvement of function is due to a reversal of muscle atrophy and fat accumulation known to occur after SSP rupture is still debated. Our previous study of late reattachment of SSP (12 weeks) failed to confirm a reversal of muscle atrophy and of fat accumulation. PURPOSE: To find out whether earlier reattachment (6 weeks) reverses atrophy and fat accumulation of the SSP. MATERIAL AND METHODS: Reattachment group: in seven rabbits unilateral supraspinatus detachment, reattachment after 6 weeks and killing 6 weeks later. Detachment group: in seven rabbits unilateral supraspinatus detachment and killing 12 weeks later. The contralateral shoulders served as controls (n=14). Determination of the supraspinatus constituents: muscle, extra- and intramuscular fat in volume and cross-sectional area. RESULTS: Muscle tissue in the reattachment group (8.6 ml+/-1s.d.=0.6) and in the detachment group (8.9 ml+/-0.9) were less than in control supraspinati (10.2 ml+/-0.9, both p<0.05). Extra- and intramuscular fat in the reattachment group (8.7%+/-3.2) was greater than in both, the detachment group (4.6%+/-3.5), and control supraspinati (2.8%+/-1.7, both p<0.05). CONCLUSION: In the rabbit, reattachment of the SSP at 6 weeks did neither reverse muscle atrophy nor fat accumulation during the ensuing 6 weeks. However, earlier reattachment (6 weeks) when compared with later reattachment (12 weeks) prevented an increase in fat accumulation. On the other hand, the delay before reattaching the tendon did not lead to an increase in muscle atrophy.

Adipose Tissue↗

Measurement of articular cartilage surface irregularity in rat knee contracture.

OBJECTIVE: To design novel quantitative methods to evaluate the irregularity of articular cartilage surface; and to apply these methods for assessment of surface irregularity in a rat knee contracture model. METHODS: A total of 117 rat knees were either immobilized or sham-operated and harvested after 2, 4, 8, 16, or 32 weeks, and 11 knees were not operated. Standardized histologic sections were digitized and the contours of femoral and tibial cartilage surfaces were delineated. The rates of change in cartilage contour were calculated. Rate of change above a defined threshold constituted surface irregularity. RESULTS: In non-operated knees, cartilage surface irregularity in femur and tibia amounted to 3.1 +/- 0.5%. Immobilized knees showed significantly more irregularities than the sham-operated knees at all time points (2 weeks: 5.3 +/- 0.6% vs 3.1 +/- 0.4%; 4 weeks: 10.5 +/- 0.9% vs 4.4 +/- 0.9%; 8 weeks: 12.0 +/- 1.8% vs 4.9 +/- 0.2%; 16 weeks: 13.7 +/- 2.0% vs 4.9 +/- 0.4%; and 32 weeks: 13.8 +/- 1.4% vs 3.4 +/- 0.6%; all p < 0.05). No difference was observed between sham-operated and non-operated knees. Increasing duration of immobilization in weeks (t) significantly correlated with more surface irregularity, described by the logarithmic formula: % irregularity = 6.6 + 2.1 ln (t), (F = 59.3, p < 0.001). This formula showed that irregularity progressed rapidly after immobilization and plateaued after 8 weeks. CONCLUSION: We designed methods to quantify cartilage surface irregularity and applied them to a contracture model. Cartilage surface irregularities appeared after 2 weeks of immobilization and progressed rapidly to plateau after 8 weeks. Combined with microscopic magnetic resonance imaging, this measurement of cartilage surface irregularity may constitute a sensitive tool to detect cartilage degeneration clinically.

Animals↗

Delayed tendon reattachment does not reverse atrophy and fat accumulation of the supraspinatus--an experimental study in rabbits.

Muscle atrophy and fat accumulation occur after rotator cuff tearing. Whether these changes are reversible after a successful repair is still unknown. Imaging allows only a semi-quantitative assessment of muscle atrophy and fat deposition. As only experimental studies permit a quantification of both, a unilateral detachment and wrapping in a polyvinylidine fluoride membrane of the supraspinatus was done in 22 rabbits. After 12 weeks, the polyvinylidine fluoride membrane was removed in 10 rabbits and the tendon inserted into a bony trough. The opposite shoulder served as control. All rabbits were killed at 24 weeks. Accumulation of fat on the muscle surface as well as between the muscle fascicles and occasionally in the sarcoplasm was increased in both experimental groups when compared to controls (non-reattached 12.8%, reattached 23.5% vs controls 5.4%; all p < 0.005). The muscle atrophy was significant (non-reattached 9.2 ml, reattached 9.1 ml vs controls 10.7 ml; both p < 0.005). Neither atrophy nor fat accumulation were reversed by surgical reattachment of the supraspinatus tendon. On the contrary, the fat accumulation was higher in the reattached group (p < 0.005). The trauma of reattachment, the delay between detachment and reattachment or an insufficient duration of recovery may have contributed to both, the lack of reversibility of supraspinatus atrophy and fat accumulation.

Adipose Tissue↗

Bilateral anterior superior iliac spine pressure ulcers: a case report.

The most frequent sites for pressure ulcers are the occiput, sacrum, ischial tuberosities, trochanters, lateral malleoli, and posterior heels. A 27-year-old woman with Wegener's granulomatosis was admitted to our rehabilitation unit after spending 65 days in an intensive care unit and 40 days in an internal medicine ward. She required mechanical ventilation because of respiratory failure. Adequate oxygenation was only achieved in the prone position. As a result, she developed bilateral anterior superior iliac spine pressure ulcers. Pressure ulcers in this location have not been reported in the literature. Complicating factors included variable levels of oxygenation, malnutrition, anemia, and steroid therapy. Complete healing, documented with serial photographs, occurred over 9 months. Although prone positioning can improve pulmonary gas exchange, it exposes the patient to unique complications. When it is required, specific care should be directed to the unusual weight-bearing surfaces to avoid pressure ulcers.

Adult↗

High collagen type I and low collagen type III levels in knee joint contracture: an immunohistochemical study with histological correlate.

We studied the levels of collagen type I and type III in the knee joints of rats immobilized for periods of 2, 4, 16 and 32 weeks and sham-operated controls. The intensities of immunostaining of the anterior and posterior synovial intima, anterior and posterior subintima, and patellar tendon were graded on a scale from 0 to 3. We found higher type I collagen levels in immobilized legs than in sham-operated legs in the anterior subintima after 4 and 16 weeks (mean score 2.1 vs 1.3, 2.2 vs 1.3, respectively) and posterior subintima after 2, 4 and 16 weeks of immobility (2.4 vs 1.7, 2.3 vs 1.5, 2.2 vs 1.3, respectively). Lower type III collagen levels were found in immobilized legs than in sham-operated legs in the anterior synovial intima after 32 weeks (1.3 vs 2.3), and posterior synovial intima and posterior subintima after 16 weeks of immobility (1.4 vs 2.8, 1.2 vs 1.7, respectively). The higher type I collagen levels in the subintima combined with lower type III suggests that the contracture process is marked by fibrosis, not new tissue proliferation. In this respect, contractures differ from granuloma, scar tissue and the pannus of inflammatory arthritis.

Animals↗