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Biomedical subjects

M Revel

Publications and source records attributed to M Revel.

At least 91 records · Page 5Linked to original sources

Forceful epidural injections for the treatment of lumbosciatic pain with post-operative lumbar spinal fibrosis.

OBJECTIVE: To evaluate the efficacy of forceful epidural corticosteroid injections in lumbosciatic pain ascribed to post-operative lumbar spinal fibrosis. METHOD: Randomized controlled study comparing forceful injections via the sacral hiatus of 125 mg prednisolone acetate + 40 ml saline (treatment group) and injections via the same route of 125 mg prednisolone acetate alone (control group). Results were compared after six and 18 months. The main evaluation criterion was a subjective assessment of overall efficacy done by the patient using a seven-level scale. RESULTS: After six months, the proportion of patients who were relieved of their sciatica was significantly higher in the forceful injection group (n = 29; 45%) than in the control group (n = 31; 19%) (p = 0.03). Success rates for low back pain were 29% and 6% in the forceful injection and control groups, respectively. Among secondary efficacy criteria, nerve root pain evaluated on a visual analog scale and by Schöber's index showed significantly greater improvement in the forceful injection group than in the control group. After 18 months, results were still in favor of the forceful injection group, with success rates of 39% for the sciatica and 31% for the low back pain. The proportion of patients who returned to work was similar in the two groups. CONCLUSION: Although mediocre overall, the results of forceful epidural corticosteroid injections are better than those of simple epidural injections of a corticosteroid alone. Given the paucity of effective treatments for lumbosciatic pain apparently due to postoperative fibrosis, forceful injections should be given a place in the treatment of this condition.

Adult↗

Development and validation of a rheumatoid hand functional disability scale that assesses functional handicap.

OBJECTIVE: To construct a functional disability scale for the rheumatoid hand and to determine if this scale also assesses functional handicap. METHODS: Outpatients and inpatients with rheumatoid arthritis (RA) according to the ACR criteria answered a set of questions on their daily hand activities. Intrarater and interrater reliability were examined. Criterion referenced validity, and convergent and divergent validities were investigated. Factor analysis followed by varimax rotation was performed. Spearman's (rs) correlation coefficients between 2 quantitative variables were examined. The level of significance was p < 0.05. RESULTS: 96 patients with RA were recruited. The provisional scale had 41 questions. The elimination process left 18 hand activity questions with 6 levels of answers. The intrarater and interrater reliabilities of the scale were 0.97 and 0.96, respectively. Correlation of the scale's total score with visual analog scale (VAS) measure of functional handicap (rs = 0.78) showed good criterion referenced validity. The scale had good convergence with Revel's Functional Index (rs = 0.91) and a moderate relation to the Hand Functional Index (HFI) (rs = 0.58). The scale had a moderate, fair, or no relation to age, morning stiffness, pain measures, and hand swelling. The scale had 3 main factors by factor analysis. An English translation of the scale was validated. CONCLUSION: We have developed a practical functional disability scale for rheumatoid hands that also assesses functional handicap. It has 18 hand activity questions and has been validated in a French population.

Adolescent↗

Methods used to develop clinical guidelines in France. The example of common lumbosciatic syndrome.

A number of Regulatory Medical References, or criteria for quality health care, have been worked out in France by a committee of physicians' union and national health insurance agency representatives, based on clinical guidelines developed using predefined methods. For each guideline, the level of evidence was evaluated, and when this level was inadequate a strong professional consensus was sought. For common lumbosciatic syndrome, the ANDEM (Agence Nationale pour le Développment de l'Evaluation Médicale, or national agency for the development of medical evaluation) worked with a multidisciplinary study group (specialists and nonspecialists, physicians from teaching hospitals, regional hospitals and private practices, primary care practitioners and specialists) whose members were from different areas of France. A computerized and manual literature search was conducted. The project director and the study group chairperson reviewed each document using predefined criteria to evaluate the methodology and level of scientific evidence. When this level was inadequate, a strong consensus expressing an opinion accepted by the medical profession was looked for. Bold type was used to indicate data resting on very high levels of evidence. The committee of physicians' union and national health insurance agency representatives used these documents to select a number of situations for which "regulatory medical references" would be useful. Each reference was written as one or a few sentences starting by "It is inappropriate to...". The study group found that subjectivity and pragmatism significantly influence the selection of diagnostic and therapeutic strategies for common lumbosciatic syndrome. The review and discussion of the high-quality literature on this condition led the study group members to modify their opinions and facilitated the development of a consensus. The group noted the paucity of scientific data on the natural history of common lumbosciatic syndrome and on the value of drug therapy and other commonly used therapeutic modalities.

France↗

5' upstream sequences of MyD88, an IL-6 primary response gene in M1 cells: detection of functional IRF-1 and Stat factors binding sites.

Transcription regulatory elements have been analyzed in upstream sequences of an Interleukin-6 (Il-6) primary response gene, MyD88. MyD88 2.3 kb mRNA is strongly and persistently induced in the course of myeloleukemic M1 cells differentiation with Il-6. MyD88 cDNA sequences were found in a region of 12 kb of mouse genomic DNA. Using Il-6 treated M1 cell RNAs, two transcription start sites have been localized, approximately 100 bp upstream from the 5' end of the cloned cDNA. We sequenced 1.4 kb of 5' genomic DNA including the first exon. In 5' of mRNA transcription start site, MyD88 nucleotidic sequence is 85% identical to 5' complementary sequences of the rat 3'-ketoacetyl CoA thiolase gene, over 1.2 kb. A DNA element conferring Il-6-inducible transcription to reporter genes, and localized 30 bp upstream of MyD88 first RNA start site, contains overlapping binding sites for cytokine activated transcription factors Stat and for the Interferon Regulatory Factor-1 and -2 (IRF-1 and IRF-2). In vitro binding assays showed that attachment of Stat factors to this element early in Il-6 treatment requires tyrosine kinase activation. IRF1, an activator of transcription, is also induced to bind to this sequence at later times. A model of persistent activation of MyD88 gene through these two types of factors is proposed.

Adaptor Proteins, Signal Transducing↗

A quantitative model of post-laminectomy scar formation. Effects of a nonsteroidal anti-inflammatory drug.

STUDY DESIGN: A quantitative model of peridural post-laminectomy fibrosis in rats was designed in this study. Concurrently, the effects of a nonsteroidal anti-inflammatory drug (ketoprofen) were evaluated. OBJECTIVES: To quantify the amount of fibrotic tissue, the extent of adhesion to the dura mater, and the cell nature and density for drug trials requiring large series of animals. SUMMARY OF BACKGROUND DATA: Most of the previous analyses of experimental post-laminectomy fibrosis were qualitative in nature. Only one quantitative analysis was reported in the rabbit, and the rat has seldom been used. The effects of nonsteroidal anti-inflammatory drugs on post-laminectomy scar formation have never been evaluated. METHODS: L5 laminectomies were performed in 32 rats. The treated group (16 rats) received a systemic injection of ketoprofen (5 mg/kg, once daily from the day before the operation to the seventh postoperative day), the other 16 rats constituted a control group. The post-laminectomy scar formation was evaluated on postoperative days 8, 15, 30, and 90 using a semiautomatic image analysis system. RESULTS: The course of post-laminectomy scar formation was similar to that described in larger animals. There was a good correlation among the measurements of fibrous tissue area obtained by 2 independent observers. The mean amount of peridural scar tissue was significantly smaller in the treated group than in the control group. The extent of adherence to the dura mater and the density of fibroblasts and fibrocytes was not different between the two groups. The density of inflammatory cells was significantly less in the treated group than in the control group only at day 8. CONCLUSION: Quantitative evaluation of post-laminectomy fibrosis can easily be performed in rats and is reproducible. This model could allow trials with drugs administered locally or systemically as preventive treatment of post-laminectomy scar formation. Nonsteroidal anti-inflammatory drugs could decrease the amount of fibrotic tissue.

Animals↗

Surface electrodes are not appropriate to record selective myoelectric activity of splenius capitis muscle in humans.

Splenius capitis (SPL) electromyograms were recorded using conventional surface and intramuscular wire electrodes simultaneously during various head-neck movements and isometric tasks to test the selectivity of surface electrodes for SPL myoelectric signals. The insertion of bipolar wire electrodes was aided by a computerized tomographical study of each subject's neck. Surface electrodes were placed over the superficial SPL area. Head motion was recorded with an electromechanical device. The selective SPL wire recordings confirmed that SPL has two main functions: ipsilateral rotation and extension. It also plays a subordinate role in ipsilateral tilting of the head. Intramuscular and surface recording results were contradictory mainly for flexion and contralateral rotation. These discrepancies appeared to be due to 'cross-talk' from adjacent muscles, particularly from the sternocleidomastoid muscle. We conclude the validity of electrode recordings is questionable for SPL and most dorsal neck muscles, especially during isometric tests.

Adult↗

Effect of topical interferon-beta on recurrence rates in genital herpes: a double-blind, placebo-controlled, randomized study.

The aim of this randomized, double-blind placebo-controlled trial was to evaluate the effect of IFN-beta cream applied at the time of recurrent eruptions of genital herpes during 6 months on the overall rate of recurrence. Therapy was initiated at the clinic for the first treated recurrence, and thereafter by the patient for early treatment of eventual subsequent eruptions. Each recurrence was ascertained at the clinic in all 35 evaluable patients. The mean recurrence rate was significantly lower in the group using IFN-beta cream than in the placebo group (p = 0.03). Complete responders without recurrence for the duration of the trial were 36.4% of all patients and 46% among women versus 15.4 and 16.6% in the placebo groups, respectively. A total of 77.3% of all patients were defined as complete or partial responders, their average recurrences/year decreasing from 11 to 2.2 (p < 0.0001). The topical episodic IFN-beta treatment was well tolerated by patients and without side effects. It is concluded that IFN-beta cream application reduces the overall rate of recurrence of genital herpes.

Administration, Topical↗

Rehabilitation of low back pain patients. A review.

Numerous methods have been developed for the rehabilitation of low back pain patients, including spinal flexion and extension exercises, lumbar spine locking in an intermediate position, enhancement of spinal and pelvic proprioceptive sensibility, swimming pool therapy, back schools, and functional restoration. Each seeks to achieve a goal assumed to be central to the prevention of a first or recurrent episode of low back pain. Goals include short-term pain relief, an improved ability to achieve self-sedation, abdominal and lumbar muscle strengthening, increased hip and lumbar spine mobility, improved lumbar and pelvic proprioceptive sensibility, intervertebral joint stabilization, lumbar posture modification and improved general fitness. Less than 30 studies meeting widely accepted validity and applicability criteria for therapeutic trials have addressed the clinical efficacy of rehabilitation in low back pain patients. Most studies of the back school approach have found no benefit. Spinal flexion and extension exercise programs have yielded short-lived improvements, with no differences across methods. There is evidence that functional restoration programs based on graded activity may provide long-term benefits including better social and occupational outcomes. We have evaluated the physical therapy methods most commonly taught to and used by physical therapists in France.

Back Pain↗

Predictors of the need for total hip replacement in patients with osteoarthritis of the hip.

RATIONALE: the natural history and risk factors for hip osteoarthritis are still unknown. OBJECTIVE: to identify factors predicting a need for total hip replacement at some time during the course of hip osteoarthritis. PATIENTS AND METHODS: outpatients evaluated between 1981 and 1986 for hip osteoarthritis were studied retrospectively. The date of diagnosis and the characteristics of the patients and hip disease at diagnosis were recorded. The risk of eventual total hip replacement was estimated using the Kaplan-Meier method. Uni- and multivariate Cox proportional hazard models were used to determine the value of each variable for predicting total hip replacement. RESULTS: we included 149 patients (50 males). The risk of total hip replacement was estimated at 36 +/- 4% five years after diagnosis. Factors with significant effects in the multivariate analysis were age older than 54 years at diagnosis (relative risk 3.15), body mass index greater than 27 (relative risk 2.97), and severe radiological joint space narrowing at diagnosis (relative risk 2.26). CONCLUSION: this study confirmed the often severe course of hip osteoarthritis and identified several factors possibly associated with rapid progression.

Aged↗

Antagonism of interferon beta on interferon gamma: inhibition of signal transduction in vitro and reduction of serum levels in multiple sclerosis patients.

Interferon gamma (IFN-gamma acts as a mediator of multiple sclerosis (MS) exacerbations through a number of biological effects, such as induction of major histocompatibility class II complexes (MHC-II), macrophage activation and potentiation of tumor necrosis factor (TNF-alpha). The clinical efficacy of interferon beta (IFN-beta) therapy in reducing exacerbations of relapsing-remitting MS has been related to antagonistic effects on various activities of IFN-gamma, including MHC-II gene induction. However, there is no model to explain such antagonistic effects of IFN-beta and IFN-gamma, and the two cytokines are also known to act synergistically against viruses and in the induction of MHC-I. We show that IFN-beta does inhibit an immediate molecular event of IFN-gamma, namely activation and DNA binding of the transcription factor Stat1. We propose a model of direct interference of the IFN-gamma and IFN-alpha,beta signal transduction pathways accounting for antagonistic effects on some genes, which in turn activate MHC-II transcription, as well as for synergistic effects on other genes. In addition, study of MS patients treated with natural IFN-beta shows that IFN-beta significantly reduces serum levels of IFN-gamma while increasing IL-4, strongly suggesting that IFN-beta also controls the relative activation of TH1- and TH2-type T lymphocytes.

Adjuvants, Immunologic↗

Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-alpha and IFN-beta.

The human interferon alpha-receptor (IFNAR gene product) is a transmembranal protein of 557 amino acids with an intracytoplasmic domain of 100 amino acids containing four tyrosines. Antibodies to a C-terminal peptide (residues 521-536) were developed which efficiently immunoprecipitate the 105 kDa IFNAR protein from detergent extracts of human cells. We show that the IFNAR protein becomes tyrosine phosphorylated within 5 min after treatment of human myeloma U266 cells with IFN-alpha 2, IFN-alpha 8 or IFN-beta. The IFNAR chain interacts with both IFN-alpha 2 and IFN-beta, as demonstrated by cross-linking. Among elements involved in signal transduction by type I IFNs, the tyrosine kinase Tyk2 but not Jak1, and the ISGF3 transcription factor subunit Stat2 (p113) but not Stat1 (p91), are found associated with the IFNAR protein. After IFN-beta treatment for 5 min, a tyrosine-phosphorylated protein of approximately 95 kDa (beta-PTyr) is found bound to IFNAR, but can be dissociated by denaturation. The beta-PTyr protein is present on the cell surface, like IFNAR, as shown by extracellular biotin tagging. The ratio of beta-PTyr to IFNAR tyrosine phosphorylation is much higher with IFN-beta than with IFN-alpha 2 or 8. Both are IFN dependent and abrogated by a monoclonal antibody which blocks IFNAR action. The beta-PTyr component may represent an important difference in the action of IFN-beta as compared with IFN-alpha in their shared receptor system.

Amino Acid Sequence↗

Interleukin-6 signaling via four transcription factors binding palindromic enhancers of different genes.

Interferons (IFNs), as well as some interleukins, growth factors, and hormones, all induce tyrosine phosphorylation of STAT1 and additional transcription factors of similar sizes. These factors are activated to translocate to nucleus and bind to enhancers of consensus sequence TTnCnnnAA (gamma-IFN activated sequence-like enhancers). In mammary cells or hybridoma B9 cells, four distinct tyrosine-phosphorylated transcription complexes activated by interleukin-6 (IL-6) and IFN-beta were observed: pIRFA and complexes I, II, and III (of increasing electrophoretic mobility). The factors have unequal affinities for enhancers of different genes; they are activated with distinct kinetics and to different extents by IL-6 and IFNs. The pIRFA band isolated from IL-6-stimulated B9 hybridoma cells revealed three DNA-interacting components: two large subunits of 91 and 98 kDa, as well as a small component of 46 kDa not seen in other complexes analyzed. One of the large pIRFA subunits may be APRF/STAT3, since pIRFA reacted with anti-APRF antibodies as do complexes I and II. However, pIRFA did not react with antibodies to STAT1, indicating STAT1 is not the other large component of pIRFA. Complex II, which reacted to anti-acute phase response factor antibodies also reacted to anti-STAT1 antibodies, whereas complex III reacted only to anti-STAT1 and was the only complex resistant to N-ethylmaleimide. By its multimeric subunit structure and its cytokine and enhancer sequence specificities, the slowly migrating pIRFA band appears as a novel tyrosine-phosphorylated transcription complex acting on a subset of gamma-IFN activated sequence-like enhancers.

Animals↗

Induction by interleukin-6 of interferon regulatory factor 1 (IRF-1) gene expression through the palindromic interferon response element pIRE and cell type-dependent control of IRF-1 binding to DNA.

The effects of interleukin-6 (IL-6) on interferon regulatory factor 1 (IRF-1) gene expression were studied in B-hybridoma B9 cells which are growth-stimulated by IL-6 and breast carcinoma T47D cells which are growth-inhibited. IL-6 induced the production of IRF-1 mRNA and protein in both cell types, but IRF-1 binding activity to its target DNA sequence was induced only in T47D cells. With B9 cells, there was no IRF-1 binding but instead strong constitutive binding of the IRF-2 repressor, indicating that binding of IRF-1 to DNA is an important regulatory step. The IRF-1 gene promoter element, palindromic IFN-response element (pIRE), was found to respond to IL-6 with high efficiency as compared with IFN-gamma or IFN-beta. On this palindromic TTC...GAA sequence, two protein complexes (pIRE-a and pIRE-b) were induced within minutes by IL-6. pIRE-b is similar to the main complex induced by IFN-gamma and contains the Stat91 protein. pIRE-a predominantly induced by IL-6 is a slowly migrating complex which does not contain Stat91 and has low affinity for IFN-gamma activated sequence (GAS)-type sequences. Comparison of the relative effects of IL-6 and IFN-gamma shows that pIRE enhancers are differently regulated than GAS elements. Distinct transcription complexes, forming in ratios dependent on the inducer, help explain how various cytokines sharing effects through Stat91 on related enhancers can produce specific patterns of gene expression. Activation of the pIRE-a factors defines a novel transcriptional activity of IL-6 in epithelial and lymphoid cells.

B-Lymphocytes↗

Similar radiologic lesions of localized Scheuermann's disease of the lumbar spine in twin sisters.

SUMMARY OF BACKGROUND DATA: Hereditary and mechanical factors are considered to be the principal etiologic factors of Scheuermann's disease. OBJECTIVES: The authors report identical twins presenting similar lesions of localized lumbar osteochondrosis, which were worse in the one twin that practiced strenuous sports activities. CONCLUSIONS: These observations suggest, at least in some of these patients, a basic role for genetic factors in the occurrence of the disease and an influence of mechanical strain on its severity.

Adolescent↗

Potential use of interleukin-6 in bone marrow transplantation: effects of recombinant human interleukin-6 after syngeneic and semiallogeneic bone marrow transplantation in mice.

The potential of recombinant glycosylated human interleukin-6 (rhIL-6) for enhancing immunohematopoietic reconstitution and survival after syngeneic and semiallogeneic bone marrow transplantation (BMT) in BALB/c mice subjected to total body irradiation (TBI) was investigated. rhIL-6 produced enhanced reconstitution of white blood cells as assessed on days 8 and 14 after syngeneic BMT and of platelets as assessed on day 10. Moreover, rhIL-6 treatment produced significant improvement of survival in lethally irradiated mice receiving either syngeneic or semiallogeneic BMT with limiting number of BM cells. This effect of IL-6 was not seen with large BM cell inocula producing high survival by themselves. rhIL-6 showed no toxic effects and did not affect the survival of mice that were lethally irradiated but not reconstituted by BM cells. However, the sensitivity of mice to sublethal irradiation was increased by rhIL-6 in the absence of BM cell transplantation. In experimental conditions inducing graft-versus-host disease (GVHD), in which lethally irradiated (BALB/c x C57BL/6)F1 mice received mixtures of BM and spleen cells from C57BL/6 donors, rhIL-6 was found to enhance GVHD manifestations. No consistent enhancement of T-cell in vitro proliferative responses to allogeneic spleen cells or T- and B-cell-dependent mitogens were seen in the splenocytes obtained from recipients of syngeneic or semiallogeneic BMT. Our data suggest that rhIL-6 may be useful in BMT procedures to enhance thrombopoiesis and hematologic recovery, as well as to increase overall survival rates. In addition, the potentiation of GVHD, which is considered to correlate with graft-versus-leukemia effects, may be of interest in enhancing GVHD-dependent antitumor effects in protocols combining radiochemotherapy with BMT.

Animals↗

Identification of mRNAs encoding two different soluble forms of the human interferon alpha-receptor.

Transcripts of the human IFN alpha-receptor (IFNAR) gene, lacking the transmembrane (TM) domain were found in human myeloma U266S cells, in addition to the transmembranal IFNAR cDNA. Two different cDNAs encoding such soluble IFNAR forms were identified. Form 1 has a deletion causing a frameshift toward the end of the extracellular (EC) domain predicting a tail of 7 amino acids. Form 2 has two in-frame deletions and conserves most of the intracytoplasmatic domain of IFNAR. The transcripts for the two soluble forms are still found in U266R cells which have lost the transmembranal IFNAR transcript. Human cells seem to have independent mechanisms to synthesize soluble IFN receptors, which may act as competitors outside the cells or carry IFN-mediated functions inside the cell.

Alternative Splicing↗