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Philippe Orcel

Publications and source records attributed to Philippe Orcel.

18 recordsLinked to original sources
PubMed2007

Paget's disease of bone in the French population: novel SQSTM1 mutations, functional analysis, and genotype-phenotype correlations.

UNLABELLED: Mutation screening of the SQSTM1 gene in 94 French patients with PDB revealed two novel point-mutations (A381V and L413F) and two new compound heterozygous genotypes (P392L/A381V and P392L/A390X). Functional analysis showed an increased level of SQSTM1/p62 protein in PDB patients and truncated forms of the protein encoded by the A390X allele. Clinical data indicate that PDB patients with SQSTM1 mutation are younger at PDB diagnosis and have more extensive bone lesions. INTRODUCTION: Paget's disease of bone (PDB) is a common chronic disease of the skeleton, with a strong genetic component. A recurrent mutation (P392L) was first identified on chromosome 5, in the Sequestosome 1 (SQSTM1) gene. Several other mutations of the SQSTM1 gene have been described in PDB patients, affecting the ubiquitin-associated domain (UBA) of the SQSTM1/p62 protein. The objectives of this study were to evaluate the frequency of the SQSTM1 mutations in French PBD patients, to study the expression of the SQSTM1/p62 protein, and to search for genotype-phenotype correlations. MATERIALS AND METHODS: Blood was obtained from 94 unrelated French PDB patients and 100 controls for mutation screening of exons 7 and 8, encoding for the UBA domain of SQSTM1. Epstein-Barr virus (EBV)-immortalized B-cell lymphocytes were established from 13 patients, giving access to functional analysis of the gene and the SQSTM1/p62 expressions using real-time PCR and Western blot. RESULTS: Mutations of the SQSTM1 gene were identified in 12 of the 94 PDB patients (13%). Eight patients carried P392L. Two novel missense mutations were identified: L413F and A381V. This A381V mutation and A390X were found in distinct patients already carriers of P392L. The SQSTM1/p62 protein expression in PDB patients increased when zero, one, or two mutations were present, and SQSTM1 truncated forms were associated with the A390X mutation. The mean age of PDB diagnosis was younger in patients with the SQSTM1 mutation. PDB was more extensive in patients who carried a SQSTM1 mutation. CONCLUSIONS: Mutations of SQSTM1 are present in the French population. PDB patients with and without the SQSTM1 mutation have an increased level of SQSTM1/p62, caused by overproduction of the protein, probably involved in the pathophysiology of PDB. The presence of the SQSTM1 mutation may be a worsening factor for PDB.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Genetics of Paget's disease of bone.

Paget's disease of bone is a chronic bone disease that affects up to 3% of Caucasians older than 55 years. The cause of Paget's disease is unknown but involves genetic factors. Familial cases display an autosomal dominant pattern of inheritance with incomplete penetrance. Genetic heterogeneity has been demonstrated and eight potential susceptibility loci identified. There is sound evidence incriminating Sequestosome 1 (SQSTM1) on the long arm of chromosome 5 (5q35-qter), of which nine mutations have been described in Paget's disease of bone. These mutations are located in exons 7 and 8, which encode a highly conserved ubiquitin-binding domain. The prevalence of SQSTM1 mutations is about 10% in France. Tests for SQSTM1 mutations should be done in patients with Paget's disease of bone, even where the family history is negative. Detection of a mutation allows evaluation of family members to ensure early diagnosis of the disease before complications develop.

Adaptor Proteins, Signal Transducing↗
PubMed2006

[Management of corticosteroid-induced osteoporosis].

Corticosteroid-induced osteoporosis is common but too often unrecognized, and its management remains insufficient. Bone loss is variable from one patient to another and thus difficult to predict, but all treated patients must be considered at risk. There are tools to assess absolute fracture risk in this case as there are for menopause-associated osteoporosis, and they may help guide the clinician in decision-making. Recent guidelines help the physician to define indications for bone mineral density testing and for therapeutic management. Bisphosphonates are currently the first-line treatment for patients with fractures or elevated fracture risk during corticosteroid treatment.

Adrenal Cortex Hormones↗
PubMed2006

Muscle involvement in sarcoidosis: a retrospective and followup studies.

OBJECTIVE: Muscle involvement is a frequent histopathologic feature of sarcoidosis, but its clinical presentation has been rarely reported and its longterm outcome is unclear. We describe the features and outcome of 5 patients with muscle sarcoidosis. METHODS: A retrospective study from hospital charts over the period 1985-2001 in 2 academic rheumatology centers. RESULTS: Muscle involvement was identified in 5 patients (3 women, 2 men) aged 37 to 61 years, out of a cohort of 45 patients with sarcoidosis. No symptomatic muscle involvement was observed in the 20 patients with Lofgren syndrome of our series. Muscle involvement was the initial feature of the disease in 2 patients. Three patients had nodular type and the 2 others the myositic type. Chronic myopathy was not observed. Followup of patients with muscle disease ranged from 30 to 144 months (mean 72.6). Prednisone was used at a starting dose from about 0.33 to 1 mg/kg/day in all patients, then progressively tapered, and was associated with use of hydroxychloroquine (HCQ) in 2 cases. One poorly compliant patient was persistently prescribed 40 mg/day prednisone and HCQ by his general practitioner and was still complaining of diffuse myalgia at the last 30-month followup visit. One patient also receiving HCQ experienced cardiac and renal relapse, leading to transient increase in steroid dosage, but remained symptom-free 3 years after steroid discontinuation. Muscle relapses occurred in the 3 other patients. Muscle symptoms disappeared after readministration of corticosteroids or increase of prednisone dosage. The first patient was symptom-free without any treatment at the last followup visit. The second was still taking 10 mg/day 144 months after disease onset because of steroid-dependent myalgia. The last patient was asymptomatic with 10 mg/day prednisone at the last evaluation. CONCLUSION: Symptomatic muscle involvement may be an initial feature of chronic, and usually the systemic form of, sarcoidosis. It responds to corticosteroid therapy, but relapse seems to be frequent.

Adult↗
PubMed2005

Prevention and treatment of glucocorticoid-induced osteoporosis in 2005.

Concern about glucocorticoid-induced osteoporosis is warranted in all patients who take glucocorticoids for longer than 3 months, in any dosage. Bone mineral density should be measured and additional risk factors sought in order to determine whether bisphosphonate therapy is appropriate. Bisphosphonate therapy should be considered in postmenopausal women and in patients whose bone densitometry T-score is less than -1.5.

Alendronate↗
PubMed2005

Systemic sarcoidosis: the "leopard-man" sign.

Systemic sarcoidosis is often diagnosed late. A 37 year-old man from the Antilles was admitted for evaluation of arthralgia, subcutaneous and cutaneous nodules, multiple enlarged lymph nodes, and an epididymal lump. He had been given a diagnosis of epididymal and nodal tuberculosis but had not responded to antitubercular agents. Gallium-67 scintigraphy showed multiple hot spots in the soft tissues, skin, muscles, mediastinum, and lachrymal glands, producing a diffuse dappled pattern. Magnetic resonance imaging of the thighs confirmed the muscular and subcutaneous involvement. Systemic sarcoidosis was diagnosed. Prednisone therapy was promptly effective. We suggest the term "dappled-body sign" or "leopard-man sign" to designate the heretofore undescribed scintigraphic pattern in our patient.

Adult↗
PubMed2005

[Paget's disease and its therapeutic management].

Bisphosphonates, potent anti-osteoclastic agents, are nowadays the first-line therapy for Paget's disease of bone. Solid evidence about efficacy and the risk/benefit ratio favor tiludronate and risedronate for oral administration and pamidronate for intravenous administration. Treatment is always intermittent, with the frequency of therapeutic sequences depending on the specific drug and the quality and duration of response. Treatment response is assessed by the extent of the reduction of biochemical markers of bone turnover, especially plasma total alkaline phosphatase. The goal of the treatment is to induce full remission, that is, normal levels of alkaline phosphatase. Bisphosphonates should be used in all patients with bone involvement that might create long-term articular (arthropathy) or neurologic (compression) complications. This aggressive strategy is the most likely to provide effective prevention of complications in the long term.

Administration, Oral↗
PubMed2005

Recommendations for monitoring antiresorptive therapies in postmenopausal osteoporosis.

Antiresorptive agents are effective in preventing and treating postmenopausal osteoporosis, provided they are taken as directed. Regular physical examinations including height measurements may fail to ensure optimal compliance. Bone mineral density (BMD) measurement is indispensable for determining whether treatment is warranted. The measurement can be repeated after 2 years at least, provided quality-control procedures are adequate. BMD changes over time should be compared to the least significant change calculated from the in vivo BMD reproducibility at the measurement center. However, BMD changes are not correlated with the fracture risk reduction induced by antiresorptive treatment. Biochemical markers for bone turnover can be monitored after only 3-6 months provided steps are taken to control for intraindividual variability. They are useful when patient compliance is poor or the treatment response inadequate.

Biomarkers↗
PubMed2005

Hypomagnesemia and chondrocalcinosis in short bowel syndrome.

Chondrocalcinosis is a result of deposition of calcium pyrophosphate dihydrate (CPPD) crystals in cartilage and fibrocartilage. Chondrocalcinosis is usually sporadic but has also been associated with a variety of metabolic diseases including hypomagnesemia. Reported cases of hypomagnesemia associated chondrocalcinosis were mostly due to renal genetic disorders such as Bartter's or Gitelman's syndrome. We describe 3 patients with chronic hypomagnesemia induced by short bowel syndrome who developed symptomatic chondrocalcinosis. CPPD crystals were identified by polarizing light microscopy in one patient. The underlying intestinal pathology was radiation enteritis in 2 patients and mesenteric arterial thrombosis in the third. Our observations strengthen the hypothesis of a role for magnesium in CPPD crystal deposition disease.

Aged↗
PubMed2004

[Diagnosis of osteoporosis].

Osteoporosis is the main cause of bone fragility. The diagnosis is suspected in the presence of low-energy traumatic fracture and/or low bone mineral density. Vertebral fractures may be asymptomatic, and they are under-diagnosed. Dual energy X-ray absorptiometry is the gold standard of bone density measurement, at the lumbar spine, and hip. Providing quality control of the device and assessments, the measurements are accurate and precise; BMD is the basis of osteoporosis diagnostic and risk fracture evaluation. Osteoporosis may be related to malignant and metabolic diseases, which must be checked before any treatment.

Female↗
PubMed2003

Paget's disease of bone.

Paget's disease of bone is characterized by an anarchic bone remodelling, associated with morphological and functional abnormalities of osteoclasts. Its prevalence and incidence rates decreased gradually over the past two decades; the reason for this remains unclear. The aetiology of the disease is still obscure, the paramyxoviral theory being very controversial. Recent advances in understanding of the disease come from genetic studies, with the identification of specific mutations in the p62-sequestosome gene, which could be involved in pathogenetic mechanisms leading to increased osteoclast activity. The disease affects one or several bone pieces, leading to bone pain, deformities, characteristic imaging features, and increased markers of bone remodelling. The long-lasting disease activity leads to complications, including arthropathies, neurological compressions, fissures or fractures and, rarely, osteosarcomatous transformation of a pagetic lesion. Potent bisphosphonates have proven their efficacy in reducing symptoms and disease activity. They are currently used as the first-line treatment with the goal of normalizing bone remodelling and, hopefully, preventing late complications.

Humans↗
PubMed2003

Prognostic value of early computed tomography in radiculopathy due to lumbar intervertebral disk herniation. A prospective study.

OBJECTIVE: To prospectively evaluate the relationship between the early computerized tomography (CT) features of disk herniation and the clinical outcome in patients with recent-onset sciatic or femoral neuralgia treated conservatively. Early CT is often used, despite the absence of data on usefulness for predicting outcomes. METHODS: Of 78 patients with sciatica or femoral neuralgia of less than 1 month's duration, presumably due to a disk herniation, 75 were found by CT to have a disk herniation at the expected level. All patients were treated conservatively. The 60 patients who were reassessed clinically after 3 months were included in the study. Based on the results of the clinical assessment, the patients were classified as having a good outcome (complete or partial recovery) or a poor outcome. CT findings were compared in these two groups. RESULTS: None of the features of disk herniation studied on the CT scans were significantly correlated with the clinical outcome. A larger herniation or presence of a free fragment was more common in the good outcome group, but the differences were not statistically significant (P= 0.07). CONCLUSION: In this study, early CT scan did not predict the clinical outcome of patients with nerve root pain from lumbar disk herniation. None of the CT criteria was associated with a poor clinical outcome. Early CT scan has no prognostic value in this setting.

Adolescent↗
PubMed2002

Bone mineral density and fracture prevalence in long-term kidney graft recipients.

BACKGROUND: Renal transplantation triggers an early bone loss that increases the subsequent risk of osteoporosis and fractures. Little is known about the long-term outcome of bone status and fracture prevalence several years after transplantation. Therefore, we conducted a cross-sectional evaluation of bone status to find out the frequency and predictors of osteoporotic fractures in late kidney graft patients. METHODS: Changes in spinal, hip, and total body bone mineral density were assessed using a DEXA Hologic QRD 1000 scanner, and fractures were quantified in all kidney graft patients presenting for routine evaluation with a minimal follow-up of 5 years after transplantation (with a mean follow-up 8.5+/-3.1 years). We measured biochemical markers of bone metabolism and collected clinical and dietary intake data. RESULTS: Fifty-nine renal graft recipients were enrolled in the study within 9 months. Osteoporosis, according to the World Health Organization definition, was observed in 31 patients (53% of the total population) and fractures occurred in 26 patients (44% of the total population and 51.6% of patients with osteoporosis). Femoral neck bone mineral density was positively correlated with patient's weight and cyclosporin current dosage. Steroid cumulative dosage correlated only to lumbar spine Z score. Dietary calcium, serum 25 hydroxyvitamin D, parathyroid hormone, and urinary N-telopeptides excretion were normal. CONCLUSIONS: These data emphasize the substantial prevalence of osteoporosis and fractures among very long-term kidney graft recipients. Therapeutic intervention in these patients is urgently needed.

Adrenal Cortex Hormones↗
PubMed2002

[Osteoporosis].

Explore the source record for details and available documents.

Aged↗
PubMed2002

[Bone diseases of the hip].

Hip pain is likely to be due to a local or regional bone disease when the hip joint is painless and of normal mobility by physical examination. Targeting the right diagnosis is easy in a patient affected by bone disease (osteoporosis, Paget's disease) or when the background of the patient is suggestive (malignancy, pregnancy). However it could be more tricky in most cases: transient osteoporosis of the hip, bone fissures, Paget's coxopathy, and tumoral cell osteolysis of bones surrounding the hip are the main causes, in addition to femoral head osteonecrosis, which is detailed in another chapter.

Bone Diseases↗
PubMed2002

Bisphosphonates in bone diseases other than osteoporosis.

The range of bone diseases in which bisphosphonates are used has extended far beyond osteoporosis during the last few years. Bisphosphonate therapy is now so well validated as to be the reference standard in Paget's disease and in the prevention of bone complications related to malignant osteolysis. Promising preliminary findings warrant the use of bisphosphonates in conditions that are either rare (fibrous dysplasia) or severe (pediatric osteogenesis imperfecta). The third category of indications encompasses many conditions in which the limited available data do not warrant widespread use: examples include reflex sympathetic dystrophy syndrome, acute back pain after a vertebral crush fracture, and chronic inflammatory joint disease not treated by glucocorticoids.

Acute Disease↗