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Biomedical subjects

François Rannou

Publications and source records attributed to François Rannou.

18 recordsLinked to original sources

Relation of inflammatory modic changes to intradiscal steroid injection outcome in chronic low back pain.

The purpose of this study was to analyze the association between the severity of inflammatory endplate changes (Modic) on MRI and the clinical response to intradiscal injection of corticosteroids (IDIC) in chronic low back pain (LBP). A total of 74 patients with LBP and inflammatory Modic changes who showed no response to 3-month conservative treatment received lumbar IDIC. Two spine specialists and a radiologist assessed independently the endplate marrow changes of the injected discs. We classified patients with a pure edema endplate changes on MRI as Modic type I (n = 37); those with a mixture of Modic type I and type II changes but predominantly edema changes as Modic I-2 (n = 25) and those with predominantly fatty changes as Modic II-1 (n = 12). The primary outcome was the change in LBP intensity between baseline and 1 month after IDIC, as measured on a visual analog scale (range 0-100 mm). At 1 month, reduction in pain score was significantly higher in the Modic I and Modic I-2 groups than in the Modic II-1 group (30.2 +/- 26.6 and 29.4 +/- 21.5 vs 5.3 +/- 25.5; P = 0.009 and P = 0.017, respectively). At 3 and 6 months, IDIC tended to be more effective in the Modic I and Modic I-2 groups but not significantly. No complications such as infection or hematoma were reported. IDIC could be a short-term efficient treatment for patients with chronic LBP and predominantly inflammatory endplate changes when conservative treatments have failed.

Adrenal Cortex Hormones↗

Oestrogens inhibit interleukin 1beta-mediated nitric oxide synthase expression in articular chondrocytes through nuclear factor-kappa B impairment.

OBJECTIVES: To investigate the presence and functionality of oestrogen receptor alpha (ERalpha) in interleukin (IL)1beta-treated rabbit articular chondrocytes in culture, and to determine the mechanisms of 17beta oestradiol (E2) effects on IL1beta-induced inducible nitric oxide synthase (iNOS) expression. METHODS: The presence and functionality of ERalpha were investigated by immunocytochemistry and transient expression of an E2-responsive reporter construct. iNOS expression and production were determined by transient expression of a chimeric iNOS promoter-luciferase construct and protein immunoblotting. Nitric oxide (NO) production was determined by the Griess reaction. DNA-binding activities of nuclear factor-kappaB (NF-kappaB) and activated protein 1 were determined by electrophoretic mobility shift assay (EMSA)-ELISA assays. Nuclear translocation of p65 was studied by immunocytochemistry. RESULTS: ERalpha was identified in the nucleus of chondrocytes. ERalpha efficiently transactivated a transiently expressed E2-responsive construct. On IL1beta treatment, ERalpha partially diffused from its nuclear localisation into the cytoplasm and its transactivation ability was impaired. Nevertheless, E2, tamoxifen and raloxifene efficiently inhibited IL1beta-induced NO production (-34%, -31% and -36%, respectively). E2 decreased IL1beta-induced iNOS protein expression (-40%). Transient expression of an iNOS promoter construct strongly suggested that iNOS expression was inhibited at the transcriptional level, and EMSA-ELISA assays showed that E2 reduced (-60%) the IL1beta-induced p65 DNA-binding capacity. Finally, the p65 nuclear translocation induced by IL1beta was also strongly decreased by E2. CONCLUSIONS: Our data support a reciprocal antagonism between oestrogens and IL1beta, ultimately resulting in the decrease of cytokine-dependent NO production through transcriptional inhibition of iNOS expression. This effect was associated with selective inhibition of p65 DNA binding and nuclear translocation.

Animals↗

Intradiscal corticosteroid injections in spondylotic cervical radiculopathy.

The purpose of this study was to evaluate treatment outcomes with intradiscal injection of corticosteroids (IDIC) in cervical spondylotic radiculopathy. Twenty consecutive patients were treated with intradiscal injection of 25 mg of acetate of prednisolone under fluoroscopic control. All patients had previously received a nonsurgical treatment for at least 3 months without success. Outcomes were assessed 1, 3 and 6 months after IDIC. Radicular pain reduction as scored on a visual analogue scale (VAS 100-mm length) was statistically significant at 1 month (19.0+/-28.0 mm; p=0.008), 3 months (25.2+/-27.5 mm; p=0.002), and 6 months (24.6+/-28.4 mm; p=0.001). In all, 40% of treated patients described at least 50% pain improvement 6 months after treatment. Four patients had complete relief of radicular pain. In conclusion, IDIC should be an alternative in the nonsurgical management of cervical spondylotic radiculopathy.

Adult↗

Cartilage breakdown in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a connective tissue disease characterized by destruction of the joint cartilage and subsequently of the underlying bone. Cartilage destruction is due to proteolysis by enzymes called metalloproteinases (MMPs), whose production and expression are regulated by numerous local mediators such as cytokines, growth factors, prostaglandins, oxygen species, and neuropeptides. MMP activation is largely due to a stimulatory effect of cytokines including IL-1beta and TNFalpha. When these cytokines bind to their membrane receptor, they set off signaling cascades, with activation of TGFbeta-activating kinase (TAK-1), of NF-kappaB by Ikappa-B kinase, of mitogen-activated protein kinases (MAP kinases), and finally of activator protein-1 (AP-1). Tissue inhibitors of MMPs (TIMPs) specifically inhibit MMPs. The interrelations between joint inflammation and joint destruction remain poorly understood. Experimental data suggest that IL-1 may be involved chiefly in joint destruction and TNF in joint inflammation. However, TNF antagonists are potent inhibitors of joint destruction in clinical practice. These results suggest that the mediators function as a network and that inhibition of a single mediator can affect the entire web. Insights gained into the innermost mechanisms of cartilage breakdown in patients with RA have led to major therapeutic breakthroughs. Thus, TNF antagonists have proved highly effective in RA. Future progress will no doubt stem from new knowledge about the extracellular mediators and intracellular signaling pathways that lead to the production and activation of enzymes responsible for cartilage degradation.

Animals↗

Validation of the French version of the fear avoidance belief questionnaire.

STUDY DESIGN: Observational prospective study. OBJECTIVE: To assess the reliability, validity, and responsiveness of the French version of the Fear Avoidance Belief Questionnaire. SUMMARY OF BACKGROUND DATA: Fear, avoidance attitudes, and belief play pivotal roles in disability perceived by patients with chronic low back pain. The Fear Avoidance Belief Questionnaire is a two-part questionnaire assessing fear, avoidance, and beliefs about professional activity and physical activity. METHODS: The Fear Avoidance Belief Questionnaire was translated by use of the forward and backward translation procedure. Test-retest reliability was assessed in 31 patients (Group 1) with the intraclass correlation coefficient and the Bland and Altman method. Construct validity was assessed in two groups of patients (Group 2, n = 147; Group 3, n = 70) with the Spearman rank correlation coefficient and factor analysis. Responsiveness was assessed in Group 3, after they underwent a functional restoration program, by the effect size and the standardized response mean. RESULTS: Test-retest reliability was good, with an intra-class correlation coefficient value of 0.88 and 0.72 for fear, avoidance, and beliefs about professional activity and physical activity, respectively. Use of the Bland and Altman method produced a homogeneous distribution of the differences, with no systematic trend observed. The expected divergent validity was observed in Groups 2 and 3. Factor analysis extracted four factors in Group 2 and the two original factors of the English Fear Avoidance Belief Questionnaire in Group 3. The lowest effect size and standardized response mean values (0.30 and 0.31, respectively) were observed with the fear, avoidance, and beliefs about professional activity. CONCLUSIONS: The psychometric properties (test-retest reliability, construct validity, and responsiveness) of the French version of the Fear Avoidance Belief Questionnaire are acceptable, and fear, avoidance, and belief can now be assessed in French-speaking patients with low back pain.

Adaptation, Psychological↗

[Rehabilitation on effort of low back pain. Functional restoration programs].

Mediocre functional prognosis In industrialised countries, chronic low back pain is the most common cause of disability and work stoppage. Conventional treatments have not reduced the impact of chronic low back pain. Hence new solutions have been searched for. FUNCTIONAL RESTORATION PROGRAMS: These programs consist in heavy and expensive multidisciplinary treatment schedules, lasting from 3 to 6 weeks. The key concepts of these programs are acceptance of pain, treatment of the problem by the patients themselves and a progression contract. POSITIVE RESULTS: Controlled studies published on the percentage of patients returning to work are positive. Maintenance of a job-attached status to the pre-injury employer is often best accomplished by the provision of suitable modified duties. Finally, results of functional restoration programs in term of return-to-work rate probably strongly depend on the social security system of the country in which such programs have been developed.

Chronic Disease↗

The ability to change of three questionnaires for neck pain.

OBJECTIVE: To assess the sensitivity to change of three algofunctional scales for neck pain. METHODS: Observational, prospective study. Patients with neck disorders were included. Pain and patients' perceived handicap assessed on visual analogue scales (VAS Pain, VAS Handicap), and functional disability measures (Neck Disability Index, Neck Pain and Disability Scale, Northwick Park Neck Pain Questionnaire) were recorded twice, at baseline and at an 11-month follow-up assessment. Sensitivity to change was assessed using the effect size (ES) and the standardised response mean (SRM), and the non-parametric Spearman's rank correlation coefficient (r) was used to assess the correlation between quantitative variable changes and patients' overall opinion. Analysis of variance (ANOVA) followed by a Tukey-test was performed to determine if the scales distinguished improved, stable, and deteriorated patients. RESULTS: Seventy-one patients (43 women, mean age 49 years) were included and evaluated twice at an interval of 11 +/- 2 months. The three scales showed good sensitivity to change. The ANOVA showed a group effect, and individual changes in the scales scores were statistically different in two-by-two comparisons (improved, stable or deteriorated patients). Changes in NPDS scores had the highest correlation with patient's overall assessment (r = 0.592). CONCLUSION: The three scales can detect changes in patients with neck disorders. Changes in NPDS score had the best correlation with patients' overall opinion concerning their neck disorder and this questionnaire should be given preference in clinical trials.

Adolescent↗

Disability induced by hand osteoarthritis: are patients with more symptoms at digits 2-5 interphalangeal joints different from those with more symptoms at the base of the thumb?

BACKGROUND: The contribution of osteoarthritis (OA) at the base of the thumb (BT) and digits 2-5 interphalangeal joints (IP) to disability in the hand has never been assessed. OBJECTIVES: To evaluate and compare disability in patients with clinical hand OA and more severe symptoms at BT or IP. DESIGN: Observational, prospective, correlational. SETTING: Rheumatology and rehabilitation departments in two tertiary care teaching hospitals. PARTICIPANTS: One hundred and sixteen patients (107 women, mean age 62+/-7 years) fulfilling the American College of Rheumatology criteria for OA in the hand, with more symptomatic BT (67 patients) or IP (49 patients). MAIN OUTCOME MEASURE: Disability assessment with Cochin hand functional scale (CHFS) was the primary outcome. Assessment of impairment by the visual analog scale of pain (VAS pain), Ritchie articular index (RAI), modified Kapandji index (mKI), Kallman radiological classification and handicap assessment with visual analog scale (VASHd) was the secondary outcome. Group comparisons were assessed by use of Student's t-test for quantitative variables and Chi-square test for categorical variables. Results of the CHFS analysis were assessed by factorial analysis followed by Varimax rotation. Correlation between scores of disability, impairment, and handicap measures were calculated with use of Spearman rank correlation coefficient. RESULTS: Demographic data, disease duration, and level of global pain were similar between the BT and IP groups. The BT and IP groups did not differ significantly according to disability and handicap level (P=0.42 and P=0.94 for CHFS total score and VASHd, respectively). Factor analysis of the CHFS revealed similar results for the two groups of patients, especially for the first extracted factor. Disability scores correlated best with global hand pain (r=0.65) in the BT group and with RAI scores (r=0.71) in the IP group. CONCLUSIONS: Disability and perceived handicap levels are comparable in clinical hand OA patients with more symptomatic BT or IP. These two groups should not be considered different during trials assessing treatments for hand OA when the primary outcome measure assesses disability.

Aged↗

Intervertebral disc degeneration: the role of the mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload.

Degeneration of the intervertebral disk (IVD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Although mechanical stress is an important modulator of the degeneration, the underlying molecular mechanism remains unclear. The association of human IVD degeneration, assessed by magnetic resonance imaging, with annulus fibrosus cell apoptosis and anti-cytochrome c staining revealed that the activation of the mitochondria-dependent apoptosome was a major event in the degeneration process. Mouse models of IVD degeneration were used to investigate the role of the mechanical stress in this process. The application of mechanical overload (1.3 MPa) for 24 hours induced annulus fibrosus cell apoptosis and led to severe degeneration of the mouse disks. Immunostaining revealed cytochrome c release but not Fas-L generation. The role of the caspase-9-dependent mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload was investigated further with the use of cultured rabbit IVD cells in a stretch device. Mechanical overload (15% area change) induced apoptosis with increased caspase-9 activity and decreased mitochondrial membrane potential. Furthermore, Z-LEHD-FMK, a caspase-9 inhibitor, but not Z-IETD-FMK, a caspase-8 inhibitor, attenuated the overload-induced apoptosis. Our results from human samples, mouse models, and annulus fibrosus culture experiments demonstrate that the mechanical overload-induced IVD degeneration is mediated through the mitochondrial apoptotic pathway in IVD cells.

Animals↗

Assessment of the test-retest reliability and construct validity of a modified WOMAC index in knee osteoarthritis.

OBJECTIVE: To assess the test-retest reliability and the construct validity of a modified version of the French-Canadian version of the WOMAC index. METHODS: Open prospective study conducted in departments of Rheumatology, Rehabilitation and Orthopedic surgery of a tertiary care teaching hospital. Eighty-eight patients with symptomatic knee osteoarthritis (OA) fulfilling the revised criteria of the American College of Rheumatology were included. The French-Canadian version of the WOMAC index was completed twice at a 3-h interval. Impairment outcome measures, patients' perceived discomfort in walking and handicap were recorded. An item-by-item analysis was performed. Test-retest reliability was assessed using the intra-class correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated using the Spearman rank correlation coefficient and a factor analysis was performed. RESULTS: Eight questions assessing function (section C) and the two questions assessing stiffness (section B) had insufficient psychometric properties and were excluded. Although test-retest reliability of the questionnaire was fair to good (0.82, 0.85, for the WOMAC section A, and modified section C, respectively), construct validity could not be demonstrated. Factor analysis of the modified form of the WOMAC extracted four factors, which differed from the a priori stratification. However, factor analysis of the modified section C extracted two factors explaining 68.4% of the variance, which could be clinically characterized. CONCLUSION: Despite its good test-retest reliability, the modified WOMAC index is not valid for assessing pain and disability induced by knee OA in a French population. Section A and modified section C could be used separately to assess, respectively, pain and function.

Adult↗

Stent implantation activates Akt in the vessel wall: role of mechanical stretch in vascular smooth muscle cells.

OBJECTIVE: The long-term efficacy of stent implantation is affected by in-stent restenosis (ISR). Multiple factors can contribute to ISR, and the underlying mechanism remains elusive. We investigated the possible role of mechanical stretch and the associated molecular signaling in ISR. METHODS AND RESULTS: Stent implantation in rat abdominal aortas induced neointima formation. Immunohistochemical studies revealed the activation of Akt in the media and neointima of the stented vessels. Western blotting showed increased phosphorylation of Akt at both Thr308 and Ser473 and phosphorylation of GSK-3beta in the stented vessels. A stretch device applying static equibiaxial stretch on cultured vascular smooth muscle cells was used to delineate the molecular mechanism underlying the stretch activation of Akt. Static mechanical stretch induced the sustained activation of Akt and its upstream phosphoinositide 3-kinase (PI3K) and the phosphorylation of GSK-3beta, its downstream effector in vascular smooth muscle cells. LY294002, a PI3K inhibitor, and N-acetylcysteine, a scavenger of reactive oxygen species, inhibited the stretch activation of Akt. Furthermore, N-acetylcysteine and wortmannin, another PI3K inhibitor, reduced the neointima formation after stent implantation. CONCLUSIONS: Mechanical stretch of the vascular wall during stent deployment may contribute to ISR by activating the Akt pathway.

Animals↗

Cyclic tensile stretch modulates proteoglycan production by intervertebral disc annulus fibrosus cells through production of nitrite oxide.

Degeneration of the intervertebral disc is the main pathophysiological process implicated in low back pain and is a prerequisite to disc herniation. Clinically, mechanical forces are important modulators of the degeneration, but the underlying molecular mechanism is not known and needs investigation to identify the biological target. The aim of this work was to study, at the molecular level, the effects of cyclic tensile stretch (CTS) on the production of proteoglycan by intervertebral disc annulus fibrosus cells since proteoglycans seem to be implicated in the dynamic process of intervertebral disc degeneration. Such cells of rabbit were cultured at high density on plates with a flexible bottom. CTS was applied with use of a pressure-operated instrument to deform the plates. With CTS at 1% elongation (1 Hz frequency), the level of (35)S-labeled neosynthesized proteoglycans that accumulated in the cellular pool or were secreted in the culture medium did not change, but at 5% elongation, the level was significantly reduced after 8 h of stimulation (30 and 21%, respectively) and further reduced at 24 h (43 and 41%, respectively). Introducing the protein synthesis inhibitor cycloheximide had no effect on this result. Neither aggrecan and biglycan expression nor proteoglycan physical properties were modified. The level of nitrite oxide production significantly increased by 3.5 times after 8 h of 5% elongation. Introducing the nitric oxide synthase (NOS) inhibitors N(G)-methyl-l-arginine or N-omega nitro-l-arginine diminished the effects of CTS on the production of nitrite oxide and proteoglycans. By contrast, introducing N-iminoethyl-l-lysine (a more specific inhibitor of inductible NOS [iNOS]) had little or no effect. Taken together, these results suggest that cNOS activation seems to be more implicated in the 5% CTS modulation of proteoglycan production than iNOS activation. These results suggest that CTS can help regulate the intervertebral disc matrix by decreasing proteoglycan production through a post-translational regulation involving nitrite oxide. This result could be of interest in the development of local therapeutic strategies aimed at controlling intervertebral disc degeneration.

Animals↗

Reliability, validity, and responsiveness of the modified Kapandji index for assessment of functional mobility of the rheumatoid hand.

OBJECTIVE: To determine the reliability, validity, and responsiveness of the modified Kapandji index (MKI). DESIGN: Prospective study. A cohort of patients planned for surgery of the wrist and/or fingers was evaluated within 48 hours before surgery and at least 6 months after surgery. SETTING: Patients were in hospitalized or private care in France. PARTICIPANTS: Patients with rheumatoid arthritis according to criteria of the American College of Rheumatology. Forty-two patients (36 women; mean age, 57.5y; range, 22-80y) were included in the reliability study. Fifty patients (42 women; mean age, 54.18y; range, 19-77y) were included in the validity study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Clinical outcome measures included the MKI, the overall mobility score of the wrist and fingers, the finger mobility score, a visual analog scale (VAS) of pain in the hands and wrists, morning stiffness duration, total score of tenderness, total score of swelling, grip and pinch strength, the Hand Functional Index (HFI), and the Cochin rheumatoid hand disability scale. Reliability was studied with the intraclass correlation coefficient (ICC) and the Bland and Altman method. Convergent and divergent validity were assessed with the Spearman correlation coefficient. Responsiveness was assessed by the paired t test, the effect size, and the standardized response mean (SRM). RESULTS: Interobserver reliability was good with an ICC of.90, and the Bland and Altman analysis showed homogeneous distribution of the differences, with no systematic trend. The MKI correlated well with the other mobility measures (HFI, the finger mobility score measured with the finger goniometer), indicating a good convergent validity, and the expected divergent validity with the other outcome measures (grip and pinch strength, total score of swelling, total score of Ritchie Articular Index, Cochin scale, VAS of pain) was observed. The 50 patients in the validity study were evaluated twice, before and after surgery, at a mean interval +/- standard deviation of 7.16+/-2.10 months (range, 6-15mo). Thirty-six patients (72%) were very satisfied or satisfied with the results of surgery, 7 (14%) were not satisfied or dissatisfied, and 7 (14%) were dissatisfied or very dissatisfied. The SRM and effect size values of the MKI were -.19 and -.10, respectively. Individual changes in the score had the best correlation (r(s)=.51) with overall patient satisfaction. CONCLUSIONS: The MKI has excellent validity and reliability. Individual changes in the score are clinically relevant. This index can be used in clinical practice and in therapeutic trials; it needs further study concerning its use for hand surgery.

Activities of Daily Living↗

Assessment of the test-retest reliability and construct validity of a modified Lequesne index in knee osteoarthritis.

OBJECTIVES: To assess the test-retest reliability and the construct validity of a modified version of the Lequesne index. METHODS: Patients with symptomatic knee osteoarthritis (OA) fulfilling the revised criteria of the American College of Rheumatology completed the Lequesne index twice at a 3-h interval. Impairment outcome measures and patients' perceived discomfort in walking and handicap were recorded. An item-by-item analysis was performed. Items having insufficient psychometric properties were excluded. Test-retest reliability was assessed using the intra-class correlation coefficient (ICC) and the Bland and Altman method. Construct validity was investigated using Spearman rank correlation coefficient and a factor analysis was performed. RESULTS: Eighty-eight patients were included. One question assessing pain (question IE) had a weak reliability (Kappa (kappa) = 0.39) and was excluded. The test-retest reliability of the modified questionnaire was excellent (ICC = 0.95). Expected convergent and divergent correlations were achieved except for visual analog scale pain (VAS P) and VAS handicap (VAS H) (0.46 and 0.40, respectively), and the "a priori" double stratification was confirmed by factor analysis, explaining 48.7% of the variance. CONCLUSION: The modified form of the Lequesne index has sufficient psychometric properties to be used to assess pain and function in knee OA in a French population.

Activities of Daily Living↗

French translation and validation of 3 functional disability scales for neck pain.

OBJECTIVE: To translate and assess the reliability and the construct validity of 3 functional disability scales for neck pain. DESIGN: Reliability and validity study. SETTING: Tertiary care teaching hospital and outpatient clinic. PARTICIPANTS: One hundred one patients (mean age, 49 y). INTERVENTION: French translations were obtained by using the "translation-backward translation" method. Adaptations were made after a pilot study. MAIN OUTCOME MEASURES: Impairment outcome measures (visual analog scale [VAS] pain, neck range of motion, morning stiffness, score of neck sensitivity, radiologic score of Kellgren) and patients' perceived handicap (VAS) were recorded at the baseline visit. Three functional disability scales (Neck Disability Index [NDI], Neck Pain and Disability Scale [NPDS], Northwick Park Neck Pain Questionnaire [NPQ]) were recorded twice, at baseline visit and 24 hours later. Reliability was assessed by using the intraclass correlation coefficient (ICC) and the Bland and Altman method. Construct (convergent and divergent) validity was investigated by using the Spearman rank correlation coefficient and a factor analysis was performed. RESULTS: Test-retest was excellent for the NPDS and NDI (ICC =.91,.93, respectively) and good for the NPQ (ICC =.84). The Bland and Altman method showed no systematic trend. Expected convergent and divergent validity were observed only for the NPDS; 3 main factors were extracted by factor analysis and explained 78% of the cumulative variance. CONCLUSION: The 3 translated scales are valid, but the NPDS seems to have the best construct validity.

Adult↗

Impact of quality scales on levels of evidence inferred from a systematic review of exercise therapy and low back pain.

OBJECTIVE: To assess whether the scale used affects levels of evidence inferred from a systematic review of studies on exercise therapy and chronic low back pain (LBP). DESIGN: Twenty trials previously analyzed in a systematic review were assessed by 2 readers using 16 different scales. SETTING: Tertiary care teaching hospital in France. PARTICIPANTS: Chronic LBP patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: For the scales allowing classification into high- and low-quality trials, a rating system with 4 levels of evidence was used to summarize conclusions drawn. The Spearman rank correlation coefficient was used to assess correlations between the scores obtained with the different scales. Interrater reliability of the scales was assessed with the intraclass correlation coefficient and the Bland and Altman method, and the degree of agreement between the readers was calculated using the kappa coefficient. RESULTS: Two of the 3 main results of the systematic review (conflicting evidence on the effectiveness of exercise therapy compared with inactive treatments; strong evidence that exercise therapy is more effective than usual care by a general practitioner) were influenced by the scale used. The range of the Spearman rank correlation coefficients between the different scales was wide (range,.49-.94), the interreader reliability of the scales was heterogeneous, and the interreader agreement was often low (kappa<or=.60 for 7/10 tests). CONCLUSIONS: The use of summary scores to identify physical therapy trials of high quality is questionable. Different quality assessment scales should probably be used to assess pharmacologic interventions and physical therapies. Development and validation of quality scales specific to physical treatments are needed.

Chronic Disease↗

Modulation of proteoglycan production by cyclic tensile stretch in intervertebral disc cells through a post-translational mechanism.

Proteoglycan production is one of the major extracellular matrix components implicated in the dynamic process of intervertebral disc degeneration. Mechanical stress is an important modulator of the degeneration, but the underlying molecular mechanism at the proteoglycan level remains unclear. The aim of this work was to study the regulation of proteoglycan production by cyclic tensile stretch applied to intervertebral disc annulus fibrosus cells. Matrix metalloproteinases do not seem to be implicated in the regulation of proteoglycan production. By contrast, nitrite oxide production is induced by cyclic tensile stretch, in a time, intensity, and frequency dependant manner. Using a non-specific nitric oxide synthases inhibitor [NG-methyl-L-arginine (L-NMA)], we suppress totally the inhibition of proteoglycan production induced by cyclic tensile stretch suggesting the implication of nitric oxide synthases in the observed phenomenon. Introducing the transcriptional inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole or a more specific inhibitor of nitric oxide synthases II [N-iminoethyl-L-lysine (L-NIL)] did not affect the decreased proteoglycan production, which suggests a post-translational regulation. In contrast, N-omega nitro-L-arginine (L-NNA) a more specific inhibitor of NOS I and III abrogated the cyclic tensile stretch-dependant inhibition of proteoglycan production. These results suggest that cyclic tensile stretch regulates proteoglycan production through a post-translational mechanism involving nitrite oxide. This result could be of interest in the development of local therapeutic strategies aimed at controlling intervertebral disc degeneration.

Animals↗