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Biomedical subjects

P Orcel

Publications and source records attributed to P Orcel.

At least 19 recordsLinked to original sources
PubMed2003

[Steroid induced osteoporosis: prevention and treatment].

PURPOSE: Corticosteroid induced osteoporosis (CIO) is the most frequent complication of long-term corticosteroid therapy, and the most frequent cause of secondary osteoporosis. New data from biological, epidemiological and therapeutic studies provide basis for optimal management of this bone disease. MAIN POINTS: Corticosteroids are responsible for both quantitative and qualitative deleterious effects on bone, through their effect on bone cells, mainly on osteoblasts (with both a decrease in osteoblast activity and an increase in apoptosis). Epidemiological studies have shown an increased risk of fractures related to CIO, even for low doses, and during the first 6 months of treatment. Relative risk is 1.3 and 2.6 for peripheral and vertebral fractures respectively. Bone mineral density, measured by dual-energy X-ray absorptiometry, is decreased at spine and hip; the risk of fracture is higher in CIO as compared to post-menopausal osteoporosis, for a similar bone density. Prevention of CIO needs the use of the minimal efficacious dose, and treatment of calcium, vitamin D and gonadal hormones insufficiencies. Patients at risk of fracture, as post-menopausal women with prevalent fractures, should receive a bisphosphonate. PERSPECTIVE: It may be possible to reduce the fracture risk in patients on long-term corticosteroid therapy.

Absorptiometry, Photon↗
PubMed2000

Bone loss. Factors that regulate osteoclast differentiation: an update.

Osteoclast activation is a critical cellular process for pathological bone resorption, such as erosions in rheumatoid arthritis (RA) or generalized bone loss. Among many factors triggering excessive osteoclast activity, cytokines such as IL-1 or tumour necrosis factor (TNF)-alpha play a central role. New members of the TNF receptor ligand family (namely receptor activator of nuclear factor-kappa B [RANK] and RANK ligand [RANKL]) have been discovered whose cross-interaction is mandatory for the differentiation of osteoclasts from hemopoietic precursors, in both physiological and pathological situations. Osteoprotegerin, a decoy receptor which blocks this interaction, decreases osteoclast activity and could have a fascinating therapeutic potential in conditions associated with upregulated bone resorption.

Cell Differentiation↗
PubMed2000

[Bone hyperresorption in multiple myeloma].

OSTEOLYSIS AND HYPERCALCEMIA: Multiple myeloma is a type B high-grade lymphoproliferative syndrome with bone tropism. Bone-related manifestations--osteolysis and hypercalcemia--are observed in 80 and 30% of cases respectively. Excessive bone resorption subsequent to destruction of the bone matrix by osteoclasts is associated with insufficient bone formation. This process plays a determining role in the development of osteolysis and hypercalcemia in multiple myeloma patients. MECHANISM OF BONE DESTRUCTION: The reality and intensity of bone destruction is clearly demonstrated by histomorphometric studies and more recently by biochemical methods using markers of bone resorption. The excessive bone resorption results from complex interactions between tumor plasma cells, bone cells, and stem cells and involves local factors and adhesion molecules. BISPHOSPHONATES: Bisphosphonates are powerful inhibitors of bone resorption. They constitute a substantial advance in the management of bone manifestation in patients with multiple myeloma. Bisphosphonates not only have a well-established curative effect in patients with tumor-induced hypercalcemia, but also inhibit disease progression in bone.

Adult↗
PubMed2000

Calcitonin receptor mRNA in mononuclear leucocytes from postmenopausal women: decrease during osteoporosis and link to bone markers with specific isoform involvement.

Calcitonin inhibits bone resorption via its receptor (CTR) on osteoclasts. Two hCTR isoforms, hCTR1 and hCTR2, give proteins that differ in their structure and signaling pathways. We investigated whether specific isoforms or quantitative changes in total hCTR mRNA were associated with high bone resorption and turnover in menopause or osteoporosis. The hCTR mRNA in mononuclear blood cells of premenopausal (PreM), healthy (PostM), and osteoporotic (OsteoP) postmenopausal women was assessed using reverse-transcriptase polymerase chain reaction. hCTR1 and hCTR2 were investigated for 59 total RNA samples, and semiquantitative analysis of total hCTR mRNA was performed for 71. Serum calcitonin, free urinary deoxypyridinoline (D-Pyr), serum bone alkaline phosphatase (SBAP), and osteocalcin (SOC) were also evaluated. Serum calcitonin levels did not differ in PostM and OsteoP. The prevalence of each isoform was similar in the three groups. Healthy postmenopausal women and OsteoP with hCTR2 had lower bone turnover (D-Pyr: 6.79 +/- 0.54, n = 25; SBAP: 11.63 +/- 1.47, n = 26; SOC: 8.31 +/- 0.58, n = 26) than those without hCTR2 (D-Pyr: 9.90 +/- 1.95, n = 5; SBAP: 21 +/- 5.19, n = 5; SOC: 11.9 +/- 2.10, n = 5; p < 0.05). Total hCTR mRNA levels were not different in PreM and PostM. By contrast, values were strikingly lower in OsteoP (0.57 +/- 0.17, n = 28) than in PostM (2. 25 +/- 0.61, n = 19, p < 0.05) and negatively correlated with bone markers values in both. We suggest that a specific isoform and amounts of total hCTR mRNA are linked to increased bone resorption in postmenopausal osteoporosis.

Adult↗
PubMed2000

Osteoarticular disorders of endocrine origin.

Endocrine diseases may present with musculoskeletal complaints, and their outcome, even after endocrine control, can be impaired by bone and joint disorders. All musculoskeletal structures, including bone, cartilage, synovium, tendons and ligaments, can be involved by some processes triggered by the endocrine disorder and its related disturbances of homeostasis, including that of growth factors. Endocrine disorders may account for 20-30% of all cases of osteopenia or osteoporosis in adults, the main causes being central and peripheral hypogonadism, endogenous and exogenous hypercorticism or hyperthyroidism, and primary hyperparathyroidism. The physician should be aware of these identifiable and treatable causes of bone loss when interpreting bone mineral density measurements. It is also valuable to evaluate bone status in patients diagnosed with these endocrine disorders. Specific bone therapeutic measures could be discussed. Other frequent musculoskeletal features include myopathy and joint and soft tissue involvement. Endocrine myopathy is frequent in most of the endocrine disorders and is non-specific since proximal painless muscle weakness associated with normal serum enzyme levels and an uncommonly encountered electromyogram myopathic pattern are present in these diseases. Soft tissue involvement is also a frequent consequence of acromegaly, hypothyroidism and diabetes mellitus. There is also a risk of nerve entrapment syndromes in these conditions. Specific arthropathies are the hallmark of acromegaly at the spinal and peripheral joints. Neuroarthropathies are a severe complication of diabetes mellitus as a result of infection, neuropathy and vasculopathy. In all these settings, the physician should be aware that endocrine disorders are part of the differential diagnosis and, conversely, that these articular and peri-articular lesions should be managed independently of the control of the underlying endocrine condition, a specific outcome being borne in mind.

Diagnosis, Differential↗
PubMed2000

Multiple domains interacting with Gs in the porcine calcitonin receptor.

The molecular basis for Gs activation by the calcitonin (CT) receptor was investigated. Based upon the analysis of conserved regions in G protein-coupled receptors, two nonoverlapping regions in the heptahelical porcine CT receptor (CTR) were selected as candidate Gs-interacting domains: the third intracellular loop residues 327-344 (KLKESQEAESHMYLKAVR, P3 region) and the C-tail residues 404-418 (KRQWNQYQAQRWAGR, P4 region). To assess their Gs-interacting function, we expressed these sequences in hybrid insulin-like growth factor II receptors in which the receptor native Gi-interacting domain was converted to CTR sequences. In COS cells transfected with either P3- or P4-substituted hybrid receptor, membrane adenylyl cyclase activity significantly increased. The up-regulated activity of cAMP was confirmed by measuring the transcriptional activity of the cAMP response element in cells expressing either hybrid receptor. A mutant CTR lacking the P4 region maintained positive cAMP response but with an attenuated maximal capacity to produce cAMP. In contrast, we could not assess the function of the P3 region using a conventional deletion method, as CT bound poorly to cells transfected with either of the two P3-deficient CTRs (one lacking the P3 region and the other lacking P3 but having the P3 sequence in reverse orientation). These data suggest that the third intracellular loop and the C-tail in CTR have domain-specific roles in Gs activation and that the hybrid receptor approach used here, combined with a conventional mutagenesis approach, is useful for intact cell analysis and functional dissection of G protein-coupled receptors.

Adenylyl Cyclases↗
PubMed2000

[Secondary osteoporosis and glucocorticoid-induced osteoporosis].

In order to assess properly the diagnosis of osteoporosis, a short clinical investigation is required to address potential causes for bone loss. Osteoporosis used to be suspected in a patient with vertebral demineralization, but nowadays it is often diagnosed in a patient with a low bone mass on a screening dual-energy X-ray absorptiometry (DEXA). In this setting, it is important for the clinician to look for secondary osteoporosis, especially in men in whom secondary osteoporosis is more frequent than in women, before discussing any specific therapy. The major causes are longterm glucocorticoid therapy, endocrine (hypogonadism, primary hyperparathyroidism, hyperthyroidism), or digestive diseases.

Adult↗
PubMed1999

Osteonecrosis-like syndrome of the medial tibial plateau can be due to a stress fracture. MR findings in 13 patients.

OBJECTIVE: To demonstrate the contribution of magnetic resonance imaging to the elucidation of mechanisms involved in "osteonecrosis-like syndrome of the medial tibial plateau". PATIENTS AND METHODS: A magnetic resonance study with sagittal and coronal sections was done in 13 patients (age range, 57-95 years) two weeks to four months into a painful syndrome meeting the definition of "osteonecrosis-like syndrome of the medial tibial plateau". Gadolinium injection was used in nine patients. Clinical symptoms resolved within a few weeks in all 13 cases. RESULTS: T1-weighted images without gadolinium showed diffuse low signal from the epiphysis (n = 12) containing an area of even lower signal seen either as a crescent-shaped subchondral image (n = 3/12) or as a linear image (n = 9/12). On postgadolinium images, the low signal was abolished except for a line of low signal parallel to the subchondral bone. T2-weighted images demonstrated diffuse high signal from the medial tibial plateau with persistence of the line of low signal (n = 8/12). CONCLUSION: Magnetic resonance imaging allows to analyze the anatomic lesion responsible for "osteonecrosis-like syndrome of the medial tibial plateau". Our magnetic resonance findings were similar to those seen in stress fractures at other sites.

Aged↗
PubMed1998

Phospholipase D- and protein kinase C isoenzyme-dependent signal transduction pathways activated by the calcitonin receptor.

The calcitonin receptor expressed by the porcine LLC-PK1 renal tubule cells is a seven-transmembrane domain, G protein-coupled receptor activating adenylyl-cyclase and phospholipase C. Salmon calcitonin stimulated dose- and time-dependent release of the phospholipase D-dependent phosphatidylcholine product [3H] choline with an EC50 = 2.5 +/-0.3 x 10(-8) M, similar to that determined for phosphoinositide metabolism (EC50 = 4.5 +/-1.0 x 10(-8)M). The hormone failed to induce release of [3H]phosphocholine and [3H]glycerophosphocholine, ruling out activation of phosphatydilcholine-specific phospholipase C and phospholipase A. Calcitonin stimulated phosphatidic acid, a product of phospholipase D-dependent phosphatydilcholine hydrolysis. Activation of phospholipase D was confirmed by release of [3H]phosphatydilethanol, a specific and stable product in the presence of a primary alcohol. Activation of calcitonin receptor induced diacylglycerol formation, with a rapid peak followed by a prolonged increase, due to activation of phospholipase C and of phospholipase D. Consequently, the protein kinase-C alpha, but not the delta isoenzyme, was cytosol-to-membrane translocated by approximately 50% after 20 min exposure to calcitonin, whereas protein kinase-C zeta, which was approximately 40% membrane-linked in unstimulated cells, translocated by approximately 19%. The human calcitonin receptor expressed by BIN-67 ovary tumor cells, although displaying higher affinity for calcitonin, failed to activate phospholipase D and protein kinase-C in response to the hormone. This receptor lacks the G protein binding consensus site due to the presence of a 48-bp cassette encoding for a 16-amino acid insert in the predicted first intracellular loop. This modification is likely to prevent the calcitonin receptor from associating to phospholipase-coupled signaling.

Animals↗
PubMed1997

Lumbar muscle rhabdomyolysis after abdominal aortic surgery.

Lumbar muscle rhabdomyolysis has been very rarely reported after surgery. The aim of this study was to determine its incidence and main characteristics in a large population undergoing abdominal aortic surgery. Over a 21-mo period, 224 consecutive patients, 209 male and 15 female, mean age 65 +/- 10 yr, underwent abdominal aortic surgery (aortic aneurysm in 142 patients and occlusive aortic degenerative disease in 82 patients). Surgical incision was a midline incision with exaggerated hyperlordosis in 173 patients and a flank incision with a retroperitoneal approach in 51 patients. Postoperative rhabdomyolysis was diagnosed in 20 patients. In these patients, 9 (4%) experienced severe low back pain, and lumbar muscle rhabdomyolysis was confirmed by tomodensitometry (n = 6) or muscle biopsy (n = 3). The remaining 11 patients had lower limb muscle rhabdomyolysis. Rhabdomyolysis occurred after surgery of longer duration, which involved more frequent visceral artery reimplantation, with longer duration of aortic clamping and greater intraoperative bleeding. Lumbar rhabdomyolysis occurred in younger patients who were more frequently obese. On first postoperative day, the mean creatine kinase (CK) value was greater in lumbar rhabdomyolysis than in lower limb rhabdomyolysis (17,082 +/- 15,003 vs 3,313 +/- 3,120 IU/L, P < 0.05). Acute renal failure and postoperative death did not occur in patients with lumbar muscle rhabdomyolysis. Lumbar rhabdomyolysis was not a rare event after abdominal aortic surgery (4%). This syndrome was characterized by postoperative low back pain of unusual severity, which required analgesic therapy, and induced a very high increase in CK with typical findings at tomodensitometry or muscle biopsy but was not associated with postoperative renal failure.

Acute Kidney Injury↗
PubMed1996

Human cord blood monocytes undergo terminal osteoclast differentiation in vitro in the presence of culture medium conditioned by giant cell tumor of bone.

Osteoclasts (OCs), which form by fusion of hematopoietic precursor cells, are typically present in large numbers in giant cell tumors of bone (GCTBs). These tumors may, therefore, contain cells which secrete factors that stimulate recruitment and differentiation of OC precursors. Multinucleated cells resembling OCs also form in cultures of human cord blood monocytes (CBMs) stimulated by 1.25 dihydroxyvitamin D3, but these cells lack the ability to form bone resorption pits, the defining functional characteristic of mature OCs. CBMs may thus require additional stimulation to form OCs; we therefore investigated whether GCTBs are a source of such a stimulus. CBMs were stimulated in long term (21 day) culture by medium conditioned by explants of GCTBs; media collected within 15 days of explant (early-CM) and after 15 days (late-CM) were employed. We also cocultured CBMs with primary GCTB-derived stromal cells as well as immortalized bone marrow stroma-derived cells. CBMs stimulated by early-CM formed resorption pits on cortical bone slices; however, stimulation by late-CM resulted in virtually no resorption. Both early-CM and late-CM increased CBM proliferation, but not the proportion of vitronectin receptor positive or multinucleated cells. Coculture of CBMs with stromal cells of GCTBs or bone marrow did not result in bone resorption, although these stromal cells (most expressing alkaline phosphatase but progressively losing parathyroid hormone receptor expression) expressed mRNA for cytokines involved in OC differentiation, including macrophage-CSF, granulocyte-macrophage-CSF, IL-11, IL-6, and stem cell factor. Our results indicate that CBMs are capable of terminal OC differentiation in vitro, a process requiring 1,25 dihydroxyvitamin D3 as well as diffusible factor(s) which can be derived from GCTB. Stromal cells of GCTB may produce such factors in vivo, but do not support OC differentiation in vitro, possibly through phenotypic instability in culture.

Acid Phosphatase↗
PubMed1996

Diversity of opinions on the management of gout in France. A survey of 750 rheumatologists.

Gout is a common disease. Although effective treatments are available for gout, there is some disagreement as to how they should be used. To study prescription patterns in gout, we conducted a questionnaire survey among 2520 rheumatologists. Seven hundred and fifty completed questionnaires were returned over a two-month period. Among respondents, 35.4% worked in a private office, 21% in a hospital and 43.6% in both. The most widely prescribed treatments in acute gout attack were colchicine alone (63%), colchicine with a nonsteroidal antiinflammatory drug (NSAID) (31.7%) and NSAID alone (5.2%), with significant variations according to the type of practice. Mean duration of treatment in acute gout was 18 +/- 16.8 days (range, 3-180 days). Mean time interval between the attack and initiation of therapy with a xanthine oxidase inhibitor was 21.6 +/- 17.2 days (range 0-180); here also, significant variations were seen according to the type of practice. Concomitant symptomatic therapy was prescribed in 97.3% of cases, for a mean duration of 54 +/- 55.4 days (range 2-365). Thirty per cent of responders never prescribed uricosuric agents. The estimated rate of occurrence of treatment-induced attacks increased with the reported interval between the attack and initiation of urate-lowering therapy. Our data demonstrate that French rheumatologists have widely diverging views on how to treat gout. Whether a waiting period is needed between an acute attack and initiation of urate-lowering therapy, and how long this period should be, are unsettled issues that deserve to be studied.

Adult↗