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Biomedical subjects

Philippe Bertin

Publications and source records attributed to Philippe Bertin.

At least 19 recordsLinked to original sources
PubMed2006

Clinical response to intra-articular injections of hylan G-F 20 in symptomatic hip osteoarthritis: the OMERACT-OARSI criteria applied to the results of a pilot study.

OBJECTIVE: To assess, using the OMERACT-OARSI criteria, the clinical response of patients presenting with symptomatic hip osteoarthritis (OA) to one intra-articular injection of hylan G-F 20. METHODS: Open-label, multi-centre, prospective, pilot study. Fifty-six patients presenting with primary hip OA, Kellgren-Lawrence grade II-III, age > or =40, with walking pain measuring 50-90 mm on a 100 mm visual analogue scale (VAS). Intra-articular injection of a single 2 ml dose of hylan G-F 20 into the hip joint under fluoroscopic guidance. A second injection could be administered at day (D) 30, 60 or 90 if pain was unchanged or returned to baseline levels. EFFICACY CRITERIA: The outcome of the first injection in the intent-to-treat (ITT) population was analysed 90 days after the injection in those patients that received a single injection, and on the day of the second injection in those patients that required two injections, using OMERACT-OARSI responder criteria (obtained from WOMAC A and C indices and the patient's global evaluation) and variation in walking pain on VAS. RESULTS: The percentage of responders according to the OMERACT-OARSI response criteria was 53.6%. An inverse correlation was observed between reduction in pain and joint space narrowing score (P=0.03). CONCLUSION: In the absence of a control group, the efficacy of the treatment cannot be determined conclusively. Nevertheless these data suggest that hylan G-F 20 is a symptomatic treatment of hip OA, particularly in less severe radiological cases. A double-blind, controlled study is required to confirm these data.

Aged↗
PubMed2006

Effects of training on general practitioners' management of pain in osteoarthritis: a randomized multicenter study.

OBJECTIVE: To evaluate the effects of a short interactive training program for general practitioners (GP) on pain management in patients with osteoarthritis (OA). METHODS: A multicenter, parallel-group study. GP were randomized to receive training on relationships and communication, pain evaluation, prescription, and negotiation of a patient contract or to a control group receiving a presentation about obtaining consent in trials. Outcomes were patient assessments of pain and functional ability. We invited 1500 GP to take part in the study. Those who volunteered to receive the training recruited outpatients from May 2001 to April 2002. Patients participating in the evaluation of the effects of the general practitioners' training had lower limb OA and pain on motion [> or = 40 mm on a visual analog scale (VAS)] and had indications for treatment with acetaminophen. The primary endpoint: sum of patient pain relief based on the daily VAS self-evaluation during the 2 weeks of the trial. RESULTS: In total, 180 GP (84 trained, 96 nontrained) enrolled 842 patients (414 and 428, respectively). Mean baseline VAS pain was 63 +/- 14 mm. Patients in the trained-GP group had better overall pain relief (316 +/- 290 mm/day vs 265 +/- 243 mm; p < 0.0001), greater improvement in Lequesne and WOMAC scores (p < 0.0001), and better overall perception of treatment (p = 0.002). Acetaminophen use was slightly higher in the trained group; however, the difference in pain relief remained statistically significant (p = 0.0003) after adjustment for this difference. CONCLUSION: This is the first study to demonstrate a positive effect of physician training on patients with a painful condition.

Aged↗
PubMed2006

[What is the frequency of cardiovascular risk factors and co-morbidity in patients with rheumatic diseases?].

Analysis of national data from the health ministry programme of reduction of the cardiovascular risks (2002-2005) shows a high frequency of cardiovascular disease and cardiovascular risk factors in the general population. It is of interest to analyse these data in relation to the practice of rheumatology. In addition, the frequency of cardiovascular pathologies is higher in patients with rheumatoid arthritis and spondylarthropothy. These notions are also very important since these two populations are often treated with non-steroidal anti-inflammatory drugs for a long duration. General knowledge shown in this article concerning the cardiovascular risk factors and co-morbidities in the patients with rheumatic pathologies allows, within the context of a therapeutic decisional strategy in rheumatology, a better estimation of the individual benefit/risk ratio of each prescription and more particularly that of non-steroidal anti-inflammatory drugs.

Adult↗
PubMed2006

[What are the cardiovascular complications of the analgesics and glucocorticoids?].

When prescribing a non-steroidal anti-inflammatory treatment but also an analgesic or a glucocorticoid, the cardiovascular risk of the patient should be assessed. The analgesics have few cardiovascular side effects and the main complications observed are linked essentially to the vagal action of the opioids. Acetaminophen is considered by several scientific societies to be the first line analgesic treatment, particularly in case of cardiovascular risk but with caution since cardiovascular toxicity of acetaminophen cannot be totally excluded. An overdose of dextropropoxyphene can result in cardiotoxicity. On the other hand, the glucocorticoids need to be prescribed cautiously, at the lowest possible dose and for the shortest possible duration due to the non-negligible cardiovascular risk, hypertension, dyslipidemia, hypokaliemia.

Acetaminophen↗
PubMed2005

Effects of the active metabolite of leflunomide, A77 1726, on cytokine release and the MAPK signalling pathway in human rheumatoid arthritis synoviocytes.

Inflammatory cytokines or soluble factors are essential in the pathogenesis of rheumatoid arthritis (RA). Leflunomide is an effective disease modifying antirheumatic drug (DMARD) in RA. The objective of the present study was to evaluate for the first time the effects of A77 1726 on cytokine (interleukin (IL)-8, IL-10, IL-11 secretion and tumor necrosis factor-alpha soluble receptor I (sTNFRI)) shedding in human RA fibroblast-like synoviocytes (FLS). At 100 microM, we observed an increase in IL-10 secretion, a decrease in IL-11 release and no effect on sTNFRI shedding and IL-8 secretion in IL-1beta-stimulated human RA FLS. Furthermore, at this dose, our results also confirmed that A77 1726 decreased IL-6 and prostaglandin E2 (PGE2) synthesis while it increased IL-1 receptor antagonist secretion (IL-1Ra). The mitogen-activated protein kinases (MAPKs) represent an attractive target for RA because they can regulate cytokine expression. At 100 microM, the effect of A77 1726 on IL-10 and IL-11 secretion seemed to be associated with the status of p38 MAPK activation. Our results confirmed the immunoregulatory action of leflunomide in the cytokine network involved in RA pathogenesis. It could shift the balance from cytokine mediated inflammation to cytokine directed inhibition of the inflammatory process.

Active Transport, Cell Nucleus↗
PubMed2005

Is restless legs syndrome underrecognized? Current management.

Restless legs syndrome (RLS) is a poorly understood sensory-motor neurological disorder whose prevalence in Caucasian populations ranges from 10% to 15%. The patient reports unpleasant sensations in the lower limbs with dysesthesia resulting in an urge to move the legs. The symptoms occur during periods of inactivity, increasing in the evening and at night. Moving the legs provides relief. In 80% of cases, polysomnography shows periodic leg movements during sleep. Patients with idiopathic RLS often report similar symptoms in family members. Secondary RLS may be due to medications, diabetes mellitus, renal failure, iron deficiency, neurological disorders, or rheumatoid arthritis. In secondary RLS, the management rests on treatment of the cause. Symptomatic treatment is warranted in patients with moderate-to-severe symptoms that adversely affect the quality of life. Dopaminergic agents are tried first. When they fail or induce adverse effects, weak opioids, benzodiazepines, anticonvulsants or, if needed, strong opioids, may be used.

Diagnosis, Differential↗
PubMed2005

Guidelines for the use of antidepressants in painful rheumatic conditions.

OBJECTIVES: Antidepressants are widely used to treat painful chronic rheumatic conditions but, contrary to neuropathic conditions, little is known about their true analgesic properties and value in these situations. Our group, which focuses on pain in rheumatology, aimed to develop recommendations for the use of antidepressants in rheumatology, based on evidence-based review of published data and expert opinion. METHOD: We identified relevant drugs and conditions and searched Medline, Embase and Pascal (1966-2003) for relevant publications in a number of European languages. We scored each study for quality, and used an expert consensus approach to formulate recommendations. RESULTS: We identified 77 studies and 12 meta-analyses and literature review on the use of antidepressant to treat painful rheumatological conditions. Forty-nine of these clinical studies were considered valid and were used to develop the recommendations. When evidence was lacking we based recommendations on our clinical experience. CONCLUSIONS: These recommendations for the treatment of painful rheumatological conditions with antidepressants were developed using evidence-based and expert consensus approaches and are the first of their kind in this field. Our review of the literature highlights the need for further, well-designed clinical studies of the use of antidepressants to treat painful rheumatological conditions.

Antidepressive Agents↗
PubMed2005

[Data recording using a personal digital assistant. Experience of prospective survey on pain in 3196 patients].

OBJECTIVE: To assess the interest of a personal digital assistant (PDA) when used as data collector in a prospective survey on pain in general practice. METHODS: Prospective, multicentre and national survey concerning the identification of 4g/24h paracetamol prescription conditions as well as the characterization of the pain justifying it. Data were collected with a dedicated PDA including an electronic visual analogue scale (VAS). It also included a data controlling program of probability, consistency, date recording and time of data entry. RESULTS: 3.196 patients were enrolled by 830 general practitioners (GPs). For 1.066 of them enrolled by 277 GPs, the consistency analysis showed an a posteriori data entry. However, for assessment of pain intensity using the VAS, the physical presence of the patient is mandatory because self-evaluation is the rule. CONCLUSION: The use of an electronic questionnaire permits the collection of good quality data and the possibility of a posteriori control and hence the identification of breaches in clinical trial protocols.

Acetaminophen↗
PubMed2004

Acetaminophen as symptomatic treatment of pain from osteoarthritis.

Osteoarthritis is a major public health burden. The incidence of osteoarthritis increases with advancing age. Symptomatic treatments aimed at alleviating the pain and thereby restoring joint function form the basis of the treatment. The chronic course requires long-term treatment with special attention to minimizing the side effects of drugs. Acetaminophen has a good risk/benefit ratio that has prompted international consensus panels to recommend its use as first-line therapy in dosages of up to 4 g/day. This review discusses safety and efficacy data from randomized double-blind trials of acetaminophen used to alleviate pain caused by osteoarthritis.

Acetaminophen↗
PubMed2004

Outcome of patients with undifferentiated chronic monoarthritis: retrospective study of 46 cases.

OBJECTIVE: To determine the natural history of undifferentiated monoarthritis of more than 3 months' duration and to evaluate the usefulness of classic diagnostic tools for identifying factors associated with outcomes. METHOD: Retrospective study of 46 patients with undifferentiated monoarthritis of more than 3 months' duration. RESULTS: Full resolution was the outcome in 50% of cases. Rheumatoid arthritis and spondyloarthropathy were the most common diagnoses in the remaining patients. HLA-B27 status was the only significant predictor of outcome: progression to spondyloarthropathy was significantly more common (P = 0.05) among HLA-B27-positive patients. Mean time to full recovery was significantly shorter than mean time to disease progression (12 vs. 45 months, P = 0.0015). Intraarticular glucocorticoid injections were effective in over 50% of patients. Arthritis relief during the month following the injection was associated with self-limited disease. The role for magnetic resonance imaging in managing patients with undifferentiated monoarthritis remains unclear. CONCLUSION: In patients with undifferentiated monoarthritis, the likelihood of a full recovery is 50%. The only significant predictor of outcome was positive HLA-B27 status, which was associated with progression to spondyloarthropathy.

Arthritis↗
PubMed2004

AstR-AstS, a new two-component signal transduction system, mediates swarming, adaptation to stationary phase and phenotypic variation in Photorhabdus luminescens.

Photorhabdus luminescens is an insect-pathogenic bacterium that forms a symbiosis with specific entomopathogenic nematodes. In this bacterium, a symbiosis-'deficient' phenotypic variant (known as the secondary variant or form II) arises at a low frequency during prolonged incubation. A knock-out mutant was generated of the regulator of a newly identified two-component regulatory system, designated AstR-AstS. Interestingly, this mutation altered the timing of phenotypic switching. Variant cells arose in the mutant strain several days before they did in the wild-type population, suggesting that AstRS is directly or indirectly involved in the genetic mechanism underlying variant cell formation. This mutation also affected motility and antibiotic synthesis. To identify AstRS-regulated genes, a comparative analysis using two-dimensional gel electrophoresis was performed. Seventeen proteins with modified synthesis in stationary phase were identified by mass spectrometry and shown to be involved in electron-transport systems, energy metabolism, iron acquisition and stress responses. The results imply that AstRS is involved in the adaptation of cells to the stationary phase, whilst negatively affecting the competitive advantage of form I cells. The link between AstRS-dependent stationary-phase adaptation and phenotypic variation is discussed.

Adaptation, Physiological↗
PubMed2004

GadE (YhiE): a novel activator involved in the response to acid environment in Escherichia coli.

In several Gram-positive and Gram-negative bacteria glutamate decarboxylases play an important role in the maintenance of cellular homeostasis in acid environments. Here, new insight is brought to the regulation of the acid response in Escherichia coli. Overexpression of yhiE, similarly to overexpression of gadX, a known regulator of glutamate decarboxylase expression, leads to increased resistance of E. coli strains under high acid conditions, suggesting that YhiE is a regulator of gene expression in the acid response. Target genes of both YhiE (renamed GadE) and GadX were identified by a transcriptomic approach. In vitro experiments with GadE purified protein provided evidence that this regulator binds to the promoter region of these target genes. Several of them are clustered together on the chromosome and this chromosomal organization is conserved in many E. coli strains. Detailed structural (in silico) analysis of this chromosomal region suggests that the promoters of the corresponding genes are preferentially denatured. These results, along with the G+C signature of the chromosomal region, support the existence of a fitness island for acid adaptation on the E. coli chromosome.

AraC Transcription Factor↗
PubMed2003

[Justification and indications for coxib therapy combined with gastro-protective agents].

UNLABELLED: IN THEORY: Combination use of a coxib with a gastro-protective agent does not appear justified since results of studies conducted on patients of all types demonstrated that the upper-digestive tract safety and tolerability profile of coxibs is good. IN SUMMARY: On the other hand, prescription-related descriptive data demonstrate that in real-life situations such a combination occurs in approximately 25% of cases. Two cases should be differentiated: in about half of cases, patients are receiving long-term therapy with a proton pump inhibitor (PPI) (for reflux oesophagitis, oesophagitis or dyspepsia) and when an NSAID is necessary, the prescribing physician logically turns to a coxib; in the other half of cases, it involves a true simultaneous co-prescription of a coxib and a gastro-protective agent (most often by far a PPI). Thus, it is only in 10-15% of patients that prescription of a coxib leads to prescription of a PPI. A SAFETY ATTITUDE: This approach can be justified by the physician's desire to be as cautious as possible in dealing a patient at high risk of GI disorders (elderly patients, previous history of digestive bleeding, co-prescription of aspirin and/or a steroid, co-morbidity) or in patients for whom the occurrence of GI bleeding would be very serious (i.e. a patient in poor condition due to multiple disorders, treatment with an oral anti-coagulant or heparin). In both cases, if the prescription of an NSAID cannot be avoided, it is therefore logical first to choose a coxib and second to prescribe simultaneously a gastro-protective agent.

Age Factors↗
PubMed2003

[Physician and patient knowledge of NSAID digestive complication risks].

REQUIREMENT: Information given to the patient is a topic which is especially of current interest, and which has been taken into account in the recent law of March 4, 2002 on patient's rights. But what about non-steroidal anti-inflammatory agents, that is, one of the most widely prescribed classes of medicinal products worldwide and which induce the highest number of sometimes fatal adverse effects (adverse drug reactions)? FREQUENT MISREADING: The aim of this update is thus to review once again the rare studies published on this topic, a review necessary prior to the formulation of recommendations regarding information to be given to the patient before prescribing him/her an NSAIDs. A review of the literature illustrates the common misunderstanding that patients have (nearly 1/4 to 1/2) regarding the potential serious gastro-intestinal adverse effects of NSAIDs. RECOMMENDATIONS: We propose that the subjects at the very least, be informed first of the risk of dyspepsia, which is the most common side-effect but usually not predictive of a serious adverse effect; then we would point out the risk of gastro-duodenal ulcer whose complications certainly are rare but can be fatal; and lastly the existence of prophylactic strategies, including the recognition of main risk factors and some medical options, such as use of synthetic prostaglandins, proton pump inhibitors or the preferential use of coxibs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Crystal structure of the N-terminal dimerisation domain of VicH, the H-NS-like protein of Vibrio cholerae.

The histone-like nucleoid structuring (H-NS) protein is a global modulator of gene expression in Gram-negative bacteria. VicH, the H-NS protein of Vibrio cholerae, regulates the expression of certain major virulence determinants implicated in the pathogenesis of cholera. We present here the 2.5A crystal structure of the N-terminal oligomerisation domain of VicH (VicH_Nt). VicH_Nt adopts the same fold and dimeric assembly as the NMR structure of Escherichia coli H-NS_Nt, thus validating this fold against conflicting data. The structural similarity of V.cholerae VicH_Nt and E.coli H-NS_Nt, despite differences in origin, system of expression, experimental conditions and techniques used, indicates that the fold determined in our studies is robust to experimental conditions. Structural analysis and homology modelling were carried out to further elucidate the molecular basis of the functional polyvalence of the N-terminal domain. Our analysis of members of the H-NS superfamily supports the suggestion that the oligomerisation function of H-NS_Nt is conserved even in more distantly related proteins.

Amino Acid Sequence↗
PubMed2003

Ralstonia metallidurans, a bacterium specifically adapted to toxic metals: towards a catalogue of metal-responsive genes.

Ralstonia metallidurans, formerly known as Alcaligenes eutrophus and thereafter as Ralstonia eutropha, is a beta-Proteobacterium colonizing industrial sediments, soils or wastes with a high content of heavy metals. The type strain CH34 carries two large plasmids (pMOL28 and pMOL30) bearing a variety of genes for metal resistance. A chronological overview describes the progress made in the knowledge of the plasmid-borne metal resistance mechanisms, the genetics of R. metallidurans CH34 and its taxonomy, and the applications of this strain in the fields of environmental remediation and microbial ecology. Recently, the sequence draft of the genome of R. metallidurans has become available. This allowed a comparison of these preliminary data with the published genome data of the plant pathogen Ralstonia solanacearum, which harbors a megaplasmid (of 2.1 Mb) carrying some metal resistance genes that are similar to those found in R. metallidurans CH34. In addition, a first inventory of metal resistance genes and operons across these two organisms could be made. This inventory, which partly relied on the use of proteomic approaches, revealed the presence of numerous loci not only on the large plasmids pMOL28 and pMOL30 but also on the chromosome. It suggests that metal-resistant Ralstonia, through evolution, are particularly well adapted to the harsh environments typically created by extreme anthropogenic situations or biotopes.

Adenosine Triphosphatases↗
PubMed2003

Aggressive systemic mastocytosis.

Systemic mastocytosis is a rare and occasionally aggressive condition that raises major diagnostic challenges. We report a case in a 72-year-old patient in whom the diagnosis of malignant mastocytosis required two bone marrow smears and three bone marrow biopsies examined using specific staining techniques. Despite interferon therapy, a mast-cell sarcoma of the sternum developed 1 year after symptom onset, followed 1 year later by acute myeloblastic leukemia, which was rapidly fatal.

Aged↗