Iron excess limits HHIPL-2 gene expression and decreases osteoblastic activity in human MG-63 cells.

UNLABELLED: In order to understand mechanisms involved in osteoporosis observed during iron overload diseases, we analyzed the impact of iron on a human osteoblast-like cell line. Iron exposure decreases osteoblast phenotype. HHIPL-2 is an iron-modulated gene which could contribute to these alterations. Our results suggest osteoblast impairment in iron-related osteoporosis. INTRODUCTION: Iron overload may cause osteoporosis. An iron-related decrease in osteoblast activity has been suggested. METHODS: We investigated the effect of iron exposure on human osteoblast cells (MG-63) by analyzing the impact of ferric ammonium citrate (FAC) and iron citrate (FeCi) on the expression of genes involved in iron metabolism or associated with osteoblast phenotype. A transcriptomic analysis was performed to identify iron-modulated genes. RESULTS: FAC and FeCi exposure modulated cellular iron status with a decrease in TFRC mRNA level and an increase in intracellular ferritin level. FAC increased ROS level and caspase 3 activity. Ferroportin, HFE and TFR2 mRNAs were expressed in MG-63 cells under basal conditions. The level of ferroportin mRNA was increased by iron, whereas HFE mRNA level was decreased. The level of mRNA alpha 1 collagen type I chain, osteocalcin and the transcriptional factor RUNX2 were decreased by iron. Transcriptomic analysis revealed that the mRNA level of HedgeHog Interacting Protein Like-2 (HHIPL-2) gene, encoding an inhibitor of the hedgehog signaling pathway, was decreased in the presence of FAC. Specific inhibition of HHIPL-2 expression decreased osteoblast marker mRNA levels. Purmorphamine, hedgehog pathway activator, increased the mRNA level of GLI1, a target gene for the hedgehog pathway, and decreased osteoblast marker levels. GLI1 mRNA level was increased under iron exposure. CONCLUSION: We showed that in human MG-63 cells, iron exposure impacts iron metabolism and osteoblast gene expression. HHIPL-2 gene expression modulation may contribute to these alterations. Our results support a role of osteoblast impairment in iron-related osteoporosis.

[Cutaneous lupus induced by etanercept in rheumatoid arthritis]. / Lupus érythémateux cutané induit par étanercept au cours de la polyarthrite rhumatoïde.

Therapy with anti-TNFalpha in rheumatoid arthritis may induce autoimmune disorders. Induction of autoantibodies is frequently observed, but lupus-like syndrome is rare and few cases only have been reported. We report a 41-year-old female, treated with etanercept for a rheumatoid arthritis, who developed a cutaneous lupus induced without any other organ involvement, associated with high ANA and DNA antibody titres. The skin biopsy and the histological analysis with immunofluorescence confirmed the diagnosis. The anti-TNFalpha treatment was stopped. Corticosteroids were increased and hydroxychloroquine administered because skin lesions persist after three months.

High-energy extracorporeal shock-wave therapy for calcifying tendinitis of the rotator cuff: a randomised trial.

In a prospective randomised trial of calcifying tendinitis of the rotator cuff, we compared the efficacy of dual treatment sessions delivering 2500 extracorporeal shock waves at either high- or low-energy, via an electromagnetic generator under fluoroscopic guidance. Patients were eligible for the study if they had more than a three-month history of calcifying tendinitis of the rotator cuff, with calcification measuring 10 mm or more in maximum dimension. The primary outcome measure was the change in the Constant and Murley Score. A total of 80 patients were enrolled (40 in each group), and were re-evaluated at a mean of 110 (41 to 255) days after treatment when the increase in Constant and Murley score was significantly greater (t-test, p = 0.026) in the high-energy treatment group than in the low-energy group. The improvement from the baseline level was significant in the high-energy group, with a mean gain of 12.5 (-20.7 to 47.5) points (p < 0.0001). The improvement was not significant in the low-energy group. Total or subtotal resorption of the calcification occurred in six patients (15%) in the high-energy group and in two patients (5%) in the low-energy group. High-energy shock-wave therapy significantly improves symptoms in refractory calcifying tendinitis of the shoulder after three months of follow-up, but the calcific deposit remains unchanged in size in the majority of patients.

Forceful sacrococcygeal injections in the treatment of postdiscectomy sciatica. A controlled study versus glucocorticoid injections.

UNLABELLED: The role of epidural fibrosis in postoperative sciatica is unclear. Few therapeutic trials have been published. We evaluated the mechanical effects of forceful saline injections through the sacrococcygeal hiatus comparatively with glucocorticoid injections. PATIENTS AND METHODS: Forty-seven patients with postdiscectomy sciatica but no evidence of compression by computed tomography or magnetic resonance imaging were included in a multicenter, randomized, controlled, parallel-group study comparing forceful injections of saline (20 ml) with or without prednisolone acetate (125 mg) to epidural prednisolone acetate (125 mg) alone. Each of the three treatments was given once a month for three consecutive months. Outcome measures were pain severity on a visual analog scale (VAS) and the scores on the Dallas algofunctional self-questionnaire on day 0, day 60, and day 120. Analysis of variance for repeated measures and Student's t test for paired series were used to evaluate the data. RESULTS: Forty-seven patients were evaluated. The VAS score improved significantly between day 0 and day 30 in the glucocorticoid group as compared to the forceful injection group (P = 0.01). No other significant differences were found across the groups. The VAS score improved steadily in the forceful injection group, producing a nearly significant difference on day 120 as compared to baseline (P = 0.08). CONCLUSION: Forceful epidural injections produced a non-significant improvement in postdiscectomy sciatica four months after surgery. Epidural glucocorticoids used alone induced short-lived pain relief.

Analysis of TNFalpha microsatellites in 35 patients with primary Sjögren's syndrome.

OBJECTIVES: Although the cause of Sjögren's syndrome remains unknown, many arguments suggest a role for both environmental and genetic factors. An association with HLA molecules has been established. Other genes on the short arm of chromosome 6 may be involved, most notably the TNF gene, which may be pivotal in the development of the epithelial lesions. METHODS: We investigated TNFalpha microsatellites in 35 patients with primary Sjogren's syndrome and in 146 healthy controls. RESULTS: The frequency of the TNFalpha10 allele showed a non-significant increase in the Sjögren's disease group (28.6% vs 15.8%; P = NS). We found significant increases when we considered only those Sjögren's disease patients with joint manifestations (N = 24; 37.5% vs 15.7%; P < 0.05) or only those with anti-Ro(SSA) antibodies (N = 10; 50% vs 15.7%; P < 0.05). CONCLUSION: Our data support a role for the TNFalpha10 allele in primary Sjögren's syndrome, particularly those forms with joint symptoms and anti-Ro(SS-A) antibodies.

[Bronchial dilatation and rheumatoid arthritis: a little known association]. / Dilatation des bronches et polyarthrite rhumatoïde: une association méconnue.

Since Ellmann's description in 1948 numerous authors have studied the respiratory manifestations associated with rheumatoid arthritis. Amongst the numerous disorders described, dilatation of the bronchi, although one of the most frequent, remains largely under-estimated. The authors report a series of 21 patients presenting jointly with both rheumatoid arthritis and bronchiectasis which was documented using thoracic computed scanning. All the subjects were female. For 20 of these patients, the appearance of bronchial suppuration preceded that of the articular manifestations by several years. Bronchial dilatation in these cases can, only with difficulty, be considered as a complication of arthritis as has been previously suggested. Rather it appears as a possible pre-disposing factor in the occurrence of the rheumatoid disease. These hypotheses explain the pathophysiological mechanisms implicated in this association are discussed.

Sciatica as the first manifestation of synovial sarcoma. Contribution of magnetic resonance imaging to the diagnosis.

A 38-year-old man presented with paralyzing sciatica as the first manifestation of synovial sarcoma of his right leg. Although neurologic symptoms sometimes occur as manifestations of synovial sarcoma, they are exceptionally inaugural. Magnetic resonance imaging is a valuable tool in patients with synovial tumors, both for establishing the diagnosis and for evaluating the extent of the lesion.

[Value of magnetic resonance imaging in the diagnosis of recurrent postoperative lumbosciatica]. / Intérêt de l'imagerie par résonance magnétique dans le diagnostic des lombosciatiques récidivantes post-opératoires.

Twelve patients who had a subsequent lumbar sciatica after surgery were evaluated with computerized tomography (C.T.) and magnetic resonance imaging (M.R.I.). The M.R.I. was performed with a 0.35 T whole body superconducting unit using spin echo technique. Two pulse sequences were realized varying the repetition time (TR) from 500 to 2,000 ms and the echo time (TE) from 28 to 60 ms. For the longer pulse, the twice echo were interpreted. The slide obtained with a surface-coil were performed in sagittal plane for the twice pulse sequences and in transaxial plane for the shorter pulse sequence. In seven cases, the results obtained with C.T. and M.R.I. were correlated. In two cases, the C.T. showed a scar formation, the M.R.I. showed a recurrent disk herniation. In three times, C.T. was unable to differentiate clearly between recurrent disk herniation and scar formation, the M.R.I. showed unequivocally on one case a scar formation and on two cases a recurrent disk herniation.

[Chemonucleolysis in the treatment of disk lumbo-radiculalgia. Cooperative study of 333 cases]. / La chimionucléolyse dans le traitement des lombo-radiculagies d'origine discale. Etude coopérative de 333 cas.

A retrospective study was carried out of 333 patients who had been treated by chemonucleolysis with chymopapain. The efficacy and safety of this treatment were evaluated and factors exerting a statistically significant effect on the quality of the results were selected from clinical and radiological data and the conditions of chemonucleolysis. Results were satisfactory in 70.5% of cases. Complications were seen in 2.8% of cases, all of which developed favorably; three of four started work again within four months, without change of job in 84% of cases. 11% of patients underwent surgery after failure of nucleolysis. There was no statistically significant evidence that results were influenced by age, sex, duration of painful episode justifying nucleolysis, the duration of the first lumbar pains or radiculalgia, the radiographic condition of the treated disc before nucleolysis or the radiographic condition of the lumbar section of the spine. There was also no significant effect of the extent of discoradicular interaction (as seen by radiography), the number of levels treated or the site of nucleolysis. In contrast, the frequency of satisfactory results was significantly higher when nucleolysis was carried out for mono-radicular sciatica, when Lasègue's sign was noted and when marked discal degeneration was seen by discography.

[Multiple bone localizations in hair cell leukemia. Efficacy of treatment with alpha 2 interferon]. / Localisations osseuses multiples au cours d'une leucémie à tricholeucocytes. Efficacité du traitement par interféron alpha 2.

We report a case of hairy cell leukemia with multiple bone lesions (skull, tibia, spine, femoral head) clinically, radiologically, and histologically documented. Radiotherapy failed to improve tibial pain. Treatment with alpha interferon resulted in bone pain improvement. Diagnoses and therapy strategies of these unusual features are discussed with respect cases to previously published in the literature.

[Chronic urticarial eruption with arthritis, papillary edema, and meningoencephalitis of childhood onset]. / Eruption urticarienne chronique avec arthrites, cedème papillaire, méningo-encéphalite à début infantile.

The authors report on a case of chronic urticarial eruption since infancy in a man who is now 27-year-old; the association of numerous chronic symptoms, principally meningo-encephalitis, polyarthritis, hepato-spleno-adenomegaly allows the authors to compare this case to those described by Prieur and Griscelli in 1981 and 16 others cases found in literature. It appears as a "systemic disease" without biological or immunological markers; it might belong to the group of chronic normocomplementemic vasculitis.

[Percutaneous spinal and sacroiliac biopsies for diagnostic purposes]. / Biopsies percutanées rachidiennes et sacro-iliaques à visée diagnostique.

The history of puncture biopsy of the spine is outlined, and a current method using a vertebral disc approach described, including principles (premedication, instrumentation, and puncture techniques), treatment of biopsy samples, and indications and contraindications of the procedure. Results are presented and compared with those reported in the literature.

[Normocalcemic hyperparathormonemia and articular chondrocalcinosis. Study of 69 patients compared to 57 controls]. / Hyperparathormonémie normocalcémique et chrondrocalcinose articulaire. Etude de 69 patients comparés à 57 sujets témoins.

The level of parathyroid hormone was measured by heterologue C terminal radio-immunological assay in 69 patients with clinical or radiological manifestations of the type seen in primary articular chondrocalcinosis. They were divided into three groups: P1 with undetermined clinical arthropathies; P2 with sub-chondral and arthosic arthropathies; P3 with radiologically definite chondrocalcinosis. They were compared with 57 control subjects broken up into four groups: T1 with chronic rheumatic arthritis, T2 with low back pain, T3 with primary hyperparathyroidism due to adenoma, and T4 with secondary hyperparathyroidism with renal insufficiency. A form of normocalcemic hyperparathormonaemia was demonstrated in more than one out of two patients in group P1 (15/29). It was seen in three-quarters of the cases in group P2 (12/16). And it was seen in more than a quarter of the cases in group P3 (7/24). This hyperparathormonaemia was statistically significant only in groups P1 and P2 compared to the normals in groups T1 and T2. The results we obtained in this study seem to be in complete concordance with those we obtained earlier in idiopathic hemochromatosis. This hyperparathormonaemia seems to regress with age and is often only discovered when the characteristic articular lesions have appeared. The discovery of normocalcemic hyperparathormonaemia several years before the appearance of the radiological signs of the disease would appear to be an important argument in favour of the diagnosis of early articular chondrocalcinosis. The existence of raised parathyroid hormone in primary articular chondrocalcinosis as well as in idiopathic hemachromatosis is special etiopathogenic interest even if there remain numerous questions concerning its origin and mode of action.