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Gilles Hayem

Publications and source records attributed to Gilles Hayem.

14 recordsLinked to original sources
PubMed2006

Predominant cervical involvement in patients with psoriatic arthritis: report of two cases.

Cervical spine involvement is common but usually delayed in patients with psoriatic arthritis. We report two cases with early and predominant involvement of the upper cervical spine. Synovitis of the atlanto-odontoid joint and fusion of multiple facet joints were noted in one patient. In the other patient, the main finding was atlanto-axial subluxation with erosions of the odontoid process and anterior arch of C1. No abnormalities were noted in the peripheral joints, sacroiliac joints, or thoracolumbar spine. Analgesics and conventional antiinflammatory agents were only minimally effective. TNFalpha antagonist therapy (infliximab followed by etanercept) in one patient and phenylbutazone therapy in the other improved the symptoms and led to shrinkage of the pannus.

Adult↗
PubMed2006

A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites.

Neutrophil NADPH oxidase plays a key role in host defense and in inflammation by releasing large amounts of superoxide and other ROSs. Proinflammatory cytokines such as GM-CSF and TNF-alpha prime ROS production by neutrophils through unknown mechanisms. Here we used peptide sequencing by tandem mass spectrometry to show that GM-CSF and TNF-alpha induce phosphorylation of Ser345 on p47phox, a cytosolic component of NADPH oxidase, in human neutrophils. As Ser345 is located in the MAPK consensus sequence, we tested the effects of MAPK inhibitors. Inhibitors of the ERK1/2 pathway abrogated GM-CSF-induced phosphorylation of Ser345, while p38 MAPK inhibitor abrogated TNF-alpha-induced phosphorylation of Ser345. Transfection of HL-60 cells with a mutated p47phox (S345A) inhibited GM-CSF- and TNF-alpha-induced priming of ROS production. This event was also inhibited in neutrophils by a cell-permeable peptide containing a TAT-p47phox-Ser345 sequence. Furthermore, ROS generation, p47phox-Ser345 phosphorylation, and ERK1/2 and p38 MAPK phosphorylation were increased in synovial neutrophils from rheumatoid arthritis (RA) patients, and TAT-Ser345 peptide inhibited ROS production by these primed neutrophils. This study therefore identifies convergent MAPK pathways on Ser345 that are involved in GM-CSF- and TNF-alpha-induced priming of neutrophils and are activated in RA. Inhibition of the point of convergence of these pathways might serve as a novel antiinflammatory strategy.

Amino Acid Sequence↗
PubMed2005

Rheumatoid nodulosis. Two cases with destructive polyarthritis after 20 years.

The term "rheumatoid nodulosis" was coined by Ginsberg in 1975 to designate a rare and distinctive form of rheumatoid disease. Anecdotal case reports suggest a benign nondestructive course, although prolonged follow-up data are usually unavailable. We describe two cases of typical rheumatoid nodulosis with follow-ups exceeding 25 years. Onset occurred at 14 and 22 years of age, respectively. Both patients presented with palindromic rheumatism, positive tests for rheumatoid factors, negative tests for other biological markers, and normal radiographs. Multiple subcutaneous nodules developed after 4 and 6 years with palindromic flares, respectively. Functional impairments and disfigurement required several surgical procedures to remove nodules. Histology was typical for rheumatoid nodules. Neither patient responded to disease-modifying anti-rheumatic drugs (gold, antimalarials, and D-penicillamine). Treatment consisted of nonsteroidal anti-inflammatory drugs combined with prednisone as needed. After 20 and 22 years of follow-up, respectively, both patients had typical rheumatoid arthritis with deformities and radiological joint destruction. In conclusion, these two cases establish that rheumatoid nodulosis can occur as a presentation of rheumatoid arthritis with a potential for severe joint damage after many years.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study.

OBJECTIVES: To characterize the risk factors, rate of occurrence, onset, nature and impact of mild to moderate muscular symptoms with high-dosage HMG-CoA reductase inhibitor (statin) therapy in general practice. METHODS: The Prédiction du Risque Musculaire en Observationnel (Prediction of Muscular Risk in Observational conditions, PRIMO) survey was an observational study of muscular symptoms in an unselected population of 7924 hyperlipidemic patients receiving high-dosage statin therapy in a usual care, outpatient setting in France. Information on patient demographics, treatment history and muscular symptoms was obtained by questionnaires. RESULTS: Multivariate analysis revealed the strongest predictors for muscular symptoms to be a personal history of muscle pain during lipid-lowering therapy (odds ratio, OR, 10.12, 95% CI 8.23-12.45; P < 0.0001), unexplained cramps (OR 4.14; 95% CI 3.46-4.95; P < 0.0001) and a history of creatine kinase (CK) elevation (OR 2.04; 95% CI 1.55-2.68; P < 0.0001). Overall, muscular symptoms were reported by 832 patients (10.5%), with a median time of onset of 1 month following initiation of statin therapy. Muscular pain prevented even moderate exertion during everyday activities in 315 patients (38%), while 31 (4%) were confined to bed or unable to work. Fluvastatin XL was associated with the lowest rate of muscular symptoms (5.1%) among individual statins. CONCLUSION: PRIMO demonstrated that mild to moderate muscular symptoms with high-dosage statin therapy may be more common and exert a greater impact on everyday lives than previously thought. Knowledge of the risk factors for muscular symptoms will allow identification and improved management of high-risk patients. The risk of muscular symptoms with fluvastatin XL treatment may be lower than with high dosages of other statins.

Aged↗
PubMed2005

Spondylitis due to Mycobacterium xenopi in a human immunodeficiency virus type 1-infected patient: case report and review of the literature.

Nontuberculous mycobacterial infections are well known to occur in patients with human immunodeficiency virus infection. However, spondylitis due to mycobacteria other than Mycobacterium tuberculosis is uncommon. We report a case of biopsy- and culture-proven Mycobacterium xenopi spondylitis in an AIDS patient and discuss approaches to diagnosis and therapy. This case serves to highlight the potential pathogenic role of this usually environmental commensal organism in severely immunosuppressed AIDS patients and uncertainties in their management, given the scarce data on appropriate therapy for this organism.

Acquired Immunodeficiency Syndrome↗
PubMed2004

[SAPHO syndrome].

Explore the source record for details and available documents.

Acquired Hyperostosis Syndrome↗
PubMed2004

Inefficacy of infliximab in primary Sjögren's syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjögren's Syndrome (TRIPSS).

OBJECTIVE: There is no effective treatment for patients with primary Sjögren's syndrome (SS). Since tumor necrosis factor alpha (TNF alpha) could be a key element in the pathogenesis of primary SS, we conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of infliximab in primary SS. METHODS: A total of 103 patients with primary SS were randomly assigned to receive infliximab infusions (5 mg/kg) or placebo at weeks 0, 2, and 6 and were followed up for 22 weeks. All patients fulfilled the new American-European Consensus Group criteria for SS and had active disease as assessed by values >50 mm on 2 of 3 visual analog scales (VAS) (0-100 mm) that evaluated joint pain, fatigue, and buccal, ocular, skin, vaginal, or bronchial dryness. A favorable overall response was defined as the patient having > or =30% improvement between weeks 0 and 10 in the values on 2 of the 3 VAS. Secondary end points were values on each VAS separately, the number of tender and swollen joints, the basal salivary flow rate, results of the Schirmer test for lacrimal gland function, the focus score on labial salivary gland biopsy, the level of C-reactive protein, and the erythrocyte sedimentation rate evaluated at weeks 0, 10, and 22, as well as quality of life evaluated by use of the generic Short Form 36 questionnaire administered at weeks 0, 10, and 22. RESULTS: At week 10, 26.5% of patients receiving placebo and 27.8% of patients treated with infliximab had a favorable overall response (P = 0.89), and at week 22, 20.4% of the placebo group and 16.7% of the infliximab group had a favorable response (P = 0.62). In addition, the 2 groups did not differ in any of the secondary end points over the 22 weeks of the trial. Severe adverse events reported in the infliximab group did not differ from those observed in previous studies. CONCLUSION: This randomized, double-blind, placebo-controlled study of an anti-TNF agent did not show any evidence of efficacy of infliximab in primary SS.

Aged↗
PubMed2003

JC virus leukoencephalopathy complicating Wegener's granulomatosis.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by the JC virus. It occurs in association with immunodepression due, for instance, to a hematological malignancy, HIV infection, or immunosuppressive therapy for an organ transplant or systemic disease. We describe the fourth reported case of PML in a patient receiving immunosuppressants for Wegener's granulomatosis. A 71-year-old woman receiving azathioprine and glucocorticoid therapy experienced onset of right-sided hemiplegia within a few days, became comatose, and died within a few days. MRI of the brain showed a subcortical lesion in the left parietal lobe generating low signal on T1 images and high signal on T2 images. The initial diagnosis was cerebral vasculitis. However, the postmortem examination showed PML. The diagnosis of PML rests on JC virus detection in the cerebrospinal fluid by PCR assay and on demonstration in a brain biopsy of the typical histological pattern with presence of the JC virus within the demyelinated lesions. No specific or effective treatments are available. Immunosuppressant drugs should be discontinued if possible.

Aged↗
PubMed2003

Inability of 99mTc-ciprofloxacin scintigraphy to discriminate between septic and sterile osteoarticular diseases.

UNLABELLED: Ciprofloxacin labeled with (99m)Tc specifically binds to various bacteria. Thus, it potentially constitutes a specific marker allowing discrimination between septic arthritis/osteomyelitis and aseptic osteoarticular diseases. The aim of this prospective study was to evaluate such properties in patients with skeletal diseases. METHODS: We prospectively investigated 2 groups of patients: patients with suspected osteoarticular infections (G1, n = 16) and a control group of patients with a presentation of osteoarticular diseases and no sign suggestive of infection (G2, n = 11). All had clinical, biologic, and radiologic evaluations and had 1-, 4-, and 24-h images from (99m)Tc-ciprofloxacin scintigraphy (370 MBq) before planned biopsy or surgery. For 23 patients, the scintigraphic results were compared with histologic and bacteriologic analyses of biopsy tissue samples; for 4 patients, the scintigraphic results were compared with the findings from 23 +/- 5 mo of follow-up. RESULTS: In G1, (99m)Tc-ciprofloxacin findings were true-positive in all 11 infected sites, true-negative in 2 cases, and false-positive in 3. In G2, (99m)Tc-ciprofloxacin was true-negative in 4 cases and false-positive in 7. Neither the location of (99m)Tc-ciprofloxacin activity nor its intensity or kinetics between 1, 4, and 24 h allowed discrimination between infection and aseptic diseases (sterile loosened joint replacement, pseudoarthrosis, or arthrosis). Sensitivity, specificity, and accuracy were 100%, 37.5%, and 63%. CONCLUSION: (99m)Tc-Ciprofloxacin scintigraphy showed good sensitivity and a high negative predictive value for the detection of bone and joint infection, but it did not discriminate between infected and aseptic osteoarticular diseases in symptomatic patients referred for surgery.

Adult↗
PubMed2002

Monoarthritis secondary to joint metastasis. Two case reports and literature review.

Synovial metastases from neoplasms are uncommon. We report two cases of knee monoarthritis due to joint metastasis. Joint fluid cytology established the diagnosis. In one patient, an epidermoid carcinoma of the ureter metastasized to the left knee. The other patient had chronic monoarthritis of the left knee unresponsive to conventional treatment and was found to have distal femoral metastases from a lung adenocarcinoma. Only 28 cases of synovial metastases from solid tumors have been reported in the literature. The knee is the most common target, the lung the most common site of the primary (12 cases), and adenocarcinoma the most common histological type (12 cases). Joint metastasis carries a poor prognosis with a mean survival of less than 5 months.

Adenocarcinoma↗
PubMed2002

NADPH oxidase priming and p47phox phosphorylation in neutrophils from synovial fluid of patients with rheumatoid arthritis and spondylarthropathy.

Superoxide anion (O2(o)-)production by neutrophil NADPH oxidase participates in arthritic joint lesion formation. Proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), interleukin 8 (IL-8) and granulocyte/macrophage-colony stimulating factor (GM-CSF) have a priming effect on neutrophil NADPH oxidase activity. NADPH oxidase activation is dependent on phosphorylation of p47phox, a cytosolic component of the enzyme. We studied O2(o)-production and p47phox phosphorylation in synovial fluid (SF) from patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA) according to TNFalpha, IL-8 and GM-CSF levels. O2(o)-production by neutrophils isolated from SF of all the arthritis patients (RA and SpA) was higher than that of circulating resting neutrophils and when stimulated with fMLP or PMA. In addition, p47phox was partially phosphorylated in SF neutrophils compared to circulating neutrophils. High levels of TNFalpha and IL-8 (but not GM-CSF) are detected in patient's SF (compared to circulating blood levels). TNFalpha levels were significantly higher in RA than in SpA SF. These results suggest that increased NADPH oxidase activity could be involved in arthritic joint inflammation through increased p47phox phosphorylation. This could be the result of the presence of high levels of priming agents such as TNFalpha and IL-8 but not GM-CSF.

Arthritis, Rheumatoid↗
PubMed2002

Differential role of neutrophils and alveolar macrophages in hepatocyte growth factor production in pulmonary fibrosis.

Neutrophils may participate in the development of lung fibrosis. Hepatocyte growth factor (HGF), a growth factor for type II pneumocytes, is produced by neutrophils. We measured the production of HGF by blood and alveolar neutrophils from patients with either idiopathic pulmonary fibrosis (n = 11) or connective tissue disease-associated pulmonary fibrosis (n = 10) and from control patients (n = 10). HGF secretion by alveolar macrophages and the expression of the HGF receptor by alveolar epithelial cells in pulmonary fibrosis were also evaluated. HGF was not detected in bronchoalveolar lavage fluid from controls. HGF concentration in the epithelial lining fluid from patients was 4-fold higher than in plasma, suggesting a local production within the alveolar space. Alveolar neutrophils secreted HGF in vitro. Basal HGF secretion by alveolar neutrophils positively correlated with HGF in the epithelial lining fluid (p = 0.05, rho = 0.582). HGF secretion by alveolar neutrophils could not be further stimulated with lipopolysaccharide, whereas HGF secretion by blood neutrophils doubled with lipopolysaccharide. Alveolar macrophages did not secrete HGF in vitro. The expression of the HGF receptor was greatly increased in the fibrotic lung, supporting the local function of HGF secreted by neutrophils. We conclude that neutrophils are a source of HGF in patients with pulmonary fibrosis.

Hepatocyte Growth Factor↗