[Principal techniques of rehabilitation. Referral to physiotherapy and speech therapy. Part I: physiotherapy].
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Persons with Disabilities↗
Biomedical subjects
Michel Revel
Publications and source records attributed to Michel Revel.
C/EBP-delta induction by gp130 signaling. Role in transition to myelin gene expressing phenotype in a melanoma cell line model.
Expression of genes encoding structural myelin proteins marks the inception of the myelinating Schwann cell (SC) phenotype. Earlier embryonic SC as well as adult non-myelinating SC produce the intermediate filament glial fibrillary acid protein (GFAP), which disappears from the myelinating SC. We previously observed that triggering of the gp130 receptor system by the IL6RIL6 ligand, comprising interleukin-6 (IL-6) fused to the soluble IL-6 receptor, induces myelin gene expression in rat embryonic dorsal root ganglia (DRG) cultures as well as in the murine melanoma cell line B16/F10.9. Study of target genes regulated by IL6RIL6 indicates a strong and selective induction of the transcriptional regulator C/EBP-delta in DRG cultures and in the F10.9 cell line. As shown here, silencing of C/EBP-delta mRNA and protein expression by introduction of small interference RNA-producing plasmids in the F10.9 cells prevented the induction of myelin protein zero (P0) and myelin basic protein (MBP) mRNAs by IL6RIL6. Doxycycline-regulated overexpression of C/EBP-delta was sufficient to induce accumulation of P0 and MBP mRNAs, the effect being selective, because C/EBP-delta did not affect several other genes strongly regulated by IL6RIL6. Interestingly, GFAP was inhibited by C/EBP-delta overexpression, leading to a modulation of the ratio between myelin gene products versus GFAP and suggesting that C/EBP-delta plays a role in the switch to a myelinating phenotype. The down-regulation of Pax3, also typical of the transition to myelinating cells, was observed after C/EBP-delta expression in correlation to P0 induction and to decrease of melanogenesis and cell growth. In cultures of dissociated cells of embryonic rat DRG, where we knocked-down the C/EBP-delta mRNA, we found an inhibition of P0 mRNA induction by IL6RIL6, showing that the role of C/EBP-delta on this myelin gene is not unique to the melanoma system.
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↗
Activation of myelin genes during transdifferentiation from melanoma to glial cell phenotype.
Induction of myelin genes occurs around birth in the last stage of Schwann cells differentiation and is reactivated in case of nerve injury. Previous studies showed that activation of the gp130 receptor system, using as ligand interleukin-6 fused to its soluble receptor (IL6RIL6), causes induction of myelin genes such as myelin basic protein (MBP) and myelin protein zero (Po) in embryonic dorsal root ganglia Schwann cells. We also reported that in murine melanoma B16/F10.9 cells, IL6RIL6 causes a shut-off of melanogenesis mediated by a down-regulation of the paired-homeodomain factor Pax3. The present work demonstrates that these IL6RIL6-treated F10.9 cells undergo transdifferentiation to a myelinating glial phenotype characterized by induction of the transcriptional activities of both Po and MBP promoters and accumulation of myelin gene products. For both Po and MBP promoters, a repression by Pax3 and stimulation by Sox10 can be demonstrated. Because after IL6RIL6-treatment, Pax3 disappears from the F10.9 cells (as it does in mature myelinating Schwann cells) whereas the level of Sox10 rather increases, we modulated the relative level of these factors and show their involvement in the induction of myelin gene expression by IL6RIL6. In addition, however, we show that a C/G-rich CACC box in the Po promoter is required for activation by IL6RIL6, as well as by ectopic Sox10, and identify a Kruppel-type zinc finger factor acting through this CACC box, which stimulates Po promoter activity.
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↗
Interferon-beta in the treatment of relapsing-remitting multiple sclerosis.
The role of interferon-beta as a disease-modifying drug (DMD) for the treatment of relapsing-remitting multiple sclerosis (RRMS) is now well established, and its efficacy has been demonstrated unequivocally in large-scale clinical trials. However, current evidence suggests that in order to increase the benefit of therapy, use of an effective drug and dosing regimen should be commenced early in the course of the disease, a finding that places new emphasis on the need for early diagnosis. Indeed, it is now known that MS lesions often develop at a subclinical level and that axonal damage occurs even in the very early stages of the disease. Moreover, such damage may be irreversible, and there is strong evidence to suggest that efficacy lost as a consequence of delay in the onset of treatment or the use of a suboptimal drug regimen cannot be regained. At present, the choice of interferon-beta is complicated by the availability of 3 different products, each with a different dosing regimen. Although the optimal interferon-beta dosing regimen for RRMS has been the focus of much discussion, the issues of dose, and particularly dosing frequency, have not been satisfactorily addressed in clinical trials until recently. Over the last 2 years, however, 3 comparative studies of interferon-beta products have been conducted. The results obtained from these recent trials underline the importance of both dose and dosing frequency and indicate that for improved efficacy in RRMS, interferon-beta therapy should be administered frequently at the highest tolerable, and thus most effective, dose.
Adjuvants, Immunologic↗
Is degenerative disk disease genetically determined?
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Aggrecans↗
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↗
HGF, SDF-1, and MMP-9 are involved in stress-induced human CD34+ stem cell recruitment to the liver.
Hematopoietic stem cells rarely contribute to hepatic regeneration, however, the mechanisms governing their homing to the liver, which is a crucial first step, are poorly understood. The chemokine stromal cell-derived factor-1 (SDF-1), which attracts human and murine progenitors, is expressed by liver bile duct epithelium. Neutralization of the SDF-1 receptor CXCR4 abolished homing and engraftment of the murine liver by human CD34+ hematopoietic progenitors, while local injection of human SDF-1 increased their homing. Engrafted human cells were localized in clusters surrounding the bile ducts, in close proximity to SDF-1-expressing epithelial cells, and differentiated into albumin-producing cells. Irradiation or inflammation increased SDF-1 levels and hepatic injury induced MMP-9 activity, leading to both increased CXCR4 expression and SDF-1-mediated recruitment of hematopoietic progenitors to the liver. Unexpectedly, HGF, which is increased following liver injury, promoted protrusion formation, CXCR4 upregulation, and SDF-1-mediated directional migration by human CD34+ progenitors, and synergized with stem cell factor. Thus, stress-induced signals, such as increased expression of SDF-1, MMP-9, and HGF, recruit human CD34+ progenitors with hematopoietic and/or hepatic-like potential to the liver of NOD/SCID mice. Our results suggest the potential of hematopoietic CD34+/CXCR4+cells to respond to stress signals from nonhematopoietic injured organs as an important mechanism for tissue targeting and repair.
Animals↗
Human reproductive cloning, embryo stem cells and germline gene intervention: an Israeli perspective.
The perspectives of applying the cloning technology to human reproduction have generated much controversy. Israel was one of the first countries to adopt (in 1998) a Law that prohibits reproductive cloning. This is a moratorium for 5 years during which neither cloning of an entire human being nor genetic changes affecting human reproductive cells will be allowed. An aim of the Law is to allow the examination of the moral, legal, and social aspects of these technologies and their implications for human dignity. With the intention of not being an obstacle to the advancement of medical genetics, the Law provides for a yearly report to the Israel Health Minister on the state of scientific knowledge in these technologies. This article reflects the 2002-3 report, relating to scientific issues and bioethical opinions in Israel and in the world on human reproductive cloning, embryonic stem cell research and germline gene manipulation. In the Jewish tradition, the primary importance of saving lives and helping suffering patients can take precedence over the fears generated by modern genetic and reproductive research. Provided that new technologies are applied for medical indications and respecting human rights and human dignity, it is legitimate to explore their beneficial potential.
Bioethics↗
Pax3 down-regulation and shut-off of melanogenesis in melanoma B16/F10.9 by interleukin-6 receptor signaling.
The microphthalmia-associated transcription factor (Mitf) is essential for melanocytic lineage development and for expression of melanogenic enzymes, such as tyrosinase. Interleukin-6 receptor/interleukin-6 chimera (IL6RIL6) induces in B16/F10.9 melanoma cells a loss of melanogenesis preceded by a sharp decrease in Mitf mRNA and gene promoter activity. In the Mitf promoter, the main cis-acting element mediating the IL6RIL6 effect is shown to be the binding site of Pax3, a paired homeodomain factor regulating among other things the development of melanocytes. Pax3 protein and mRNA levels decline steadily after IL6RIL6 treatment, and overexpression of an ectopic Pax3 cDNA suppresses the Mitf promoter inhibition. Loss of the synergism between Pax3 and Sox10, a high mobility group domain costimulatory factor, seems to be critical in the rapid decrease in Mitf gene expression. The Pax3 down-regulation in IL6RIL6-induced F10.9 cell is linked to growth arrest and transdifferentiation to a glial cell phenotype. IL6RIL6 stimulates the interleukin-6 family cytokine receptor gp130, leading to the rapid phosphorylation of Stat3 on tyrosine 705. This phosphorylation is required for Pax3 down-regulation and Mitf promoter silencing since these are inhibited in F10.9 cells overexpressing the Stat3 DN-mutant Y705F.
Animals↗
Beneficial effects of information leaflets before spinal steroid injection.
UNLABELLED: How beneficial is the provision of information leaflets to low back pain patients before steroid injection under fluoroscopy? OBJECTIVES: To compare the value of information leaflets with verbal information on steroid injection under fluoroscopy. METHODS: Alternate month design. One hundred and twenty-three low back pain patients hospitalized for steroid injection under fluoroscopy were enrolled in the trial. Fifty-two patients received both written standardized information and non-standardized verbal information (intervention group), seventy one patients received only non-standardized verbal information (control group). Anxiety assessed at baseline evaluation and just before the injection; satisfaction related to the information received assessed on discharge day; knowledge about steroid injection assessed 4 hours and 1 month after the injection. RESULTS: Patients had a high anxiety level at baseline evaluation. Written standardized information did not decrease significantly anxiety (P = 0.068) before the injection, had no effect on pain during the injection, but increased patients' knowledge about the adverse effects on the day of injection and 1 month later (P = 0.040 and P = 0.084 respectively), and improve satisfaction with information received about potential complications of the steroid injections (P = 0.018). CONCLUSIONS: Providing an information leaflet to low back pain patents undergoing steroid injection under fluoroscopy tends to reduce state anxiety, and increases patients' knowledge and satisfaction with information about the risks of the injection.
Adult↗
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↗
Reproduction by cloning: a new ethical challenge.
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Cloning, Organism↗
Value of Percutaneous Treatments of the Lumbar Spine in Back and Nerve Root Pain.
Percutaneous treatments are widely used in low back pain (LBP) and nerve root pain. The only treatment assessed in several controlled studies is chemonucleolysis. Automated percutaneous discectomy was proven non-effective in two controlled studies and manual percutaneous discectomies still require appropriate evaluation. The problem of facet joint treatments is to select patients with LBP originating from these joints. Epidural injections of steroids are the cornerstone of the medical management in sciatica, but the data from controlled studies are inconsistent. Further studies are needed to give guidelines on the best time after the onset of radicular pain, volume, number, and timing of the injections. In addition, the problem of misplacement of the needle should be considered. Foraminal injections of steroids under fluoroscopic control also need controlled studies. Endoscopic procedures in the epidural space should be studied by leading teams representing the spine specialists in the community. Finally, in addition to their technical aspect, each new percutaneous procedure should be evaluated by a stringent methodology to assess the risk-benefit.
Journal Article↗
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↗
[The concept of discolysis in intervertebral disk disease].
Intervertebral disk disease has multiple radiological expressions and is probably multifactorial, although being generally considered univocal. Mechanical factors have been the best studied etiological factors and appear to be capable of starting and aggravating the different components of disk degeneration. This process also depends on genetic influences such as a collagen type IX mutation, a polymorphism in the aggrecan gene and a polymorphism in the vitamin D receptor gene. Intervertebral disk cells produce numerous cytokines with catabolic and anabolic activity. One of the elements of disk degeneration could be the unbalance between catabolic/inflammatory cytokines (IL1, TNF alpha...) and anabolical/antiinflamatory cytokines (IL 10, IL1 Ra, growth factors...). The main driver force of disk matrix destruction is the unbalance between metaloproteases (collagenases, stromelysines and gelatinases) and its natural inhibitors. It is this process that characterizes the active disk disease. It implies a reduction in the radiological intervertebral space in a few months and a vertebral plate oedema sign in MRI, around degenerated disks. This is clinically manifested as pseudo-inflammatory pain, with increased severity during the morning. These periods of active disk disease respond to non steroidal anti-inflammatory drugs and to steroids, particularly when locally administered. The evidence of the existence of an active disk disease has not only clinical and management pertinence but also scientific, as it allows to better understand the process of disk destruction.
Humans↗