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Thirty-five male patients, aged 34–79 yr, with definite rheumatoid arthritis (RA) were recruited from out-patient clinics and randomized to receive monthly injections of testosterone enanthate 250 mg or placebo as an adjunct therapy for 9 months. Endpoints included disease activity parameters and bone mineral density (BMD). At baseline, there were negative correlations between the ESR and serum testosterone (r = - 0.42, P < 0.01) and BMD (hip, r = − 0.65, P < 0.01). A total of 29.6% of all patients had at least one vertebral fracture, most having multiple fractures. Back pain, however, was not more prevalent in fracture patients (55% vs 50%). Disease activity was significantly higher in the fracture group (joint score P < 0.05, rheumatoid factor P < 0.01). Thirty patients completed the trial, 15 receiving testosterone and 15 receiving placebo. There were significant rises in serum testosterone, dihydrotestosterone and oestradiol in the treatment group. There was no significant effect of treatment on disease activity overall, five patients receiving testosterone underwent a ‘flare’. Differences in mean BMD following testosterone or placebo were non-significant (spine: +1.2% vs −1.1%; femur −0.3% vs +0.3%). There was no suggestion of a positive effect of testosterone on disease activity in men with RA. [ABSTRACT FROM PUBLISHER]

Presents a letter to the editor about rheumatoid arthritis, kaposi's sarcoma and drug interaction published in the May 1, 1997 issue of the "Journal of European Academy of Dermatology and Venereology".

Autoimmune and autoinflammatory diseases (AIDs) are a heterogeneous group of diseases. They can occur in childhood and account for significant morbidity and mortality. Transitioning from pediatric to adult healthcare can be difficult for patients and their families. It can interfere with patient follow-up and management, and eventually lead to complications. Although recommendations exist for the successful transition of patients with chronic diseases, few are specifically adapted to children and adults with AIDs (Suris et al., 2015-Solau-Gervais, 2012). The French working group on transition of the rare autoimmune and autoinflammatory diseases presents its reflections and recommendations for a successful transition. Preparation for transition should start early. Its goals are to empower adolescents by providing them with the knowledge to manage their own care, respond appropriately to changes in their condition, and evolve within the adult healthcare system. This requires the active participation of the patient, his or her family, as well as the pediatric and adult medical teams. The transition process involves multidisciplinary care and dedicated therapeutic education programs. Finally, the identification of medical specialists by region, trained in rare AIDs and accompanied by expert patients, may improve the management of patients with rare AIDs from adolescence to adulthood., (Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Bisphosphonates are indicated for the treatment of bone lesions in patients with solid tumours or multiple myeloma. Bisphosphonates have proven their effectiveness in reducing the number of bone complications (hypercalcemia, pain, disease-related fractures, spinal cord compression) and delaying their occurrence in patients with bone tumours; they have also been shown to reduce the need for bone surgery and palliative or pain-relieving radiotherapy in these patients. International recommendations for the treatment of bone lesions related to malignant solid tumours and multiple myeloma have been established. We have elaborated clinical practice guidelines on the use of bisphosphonates to assist treatment decision-making in bone oncology. The guide contains decision trees and tables with information to guide pre-treatment evaluation and patient follow-up, as well as indications and conditions of use of bisphosphonates. In 2007, the regional cancer network of Rhône-Alpes, ONCORA, formed a working group (GIP ONCORA) to elaborate the guideline. The final version was then discussed and adopted at a plenary session in July 2009, during a collaborative workshop on supportive care recommendations organized by ONCORA and the regional cancer network of Lorraine., (Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

We report the results of the cross-cultural adaptation and validation into the French language of two health status instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health related quality of life instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. Five hundred children were enrolled including 306 patients with JIA classified into systemic (23%), polyarticular (22%), extended oligoarticular (25%), and persistent oligoarticular (30%) subtypes, and 194 healthy children. Both instruments were reliable with intra-class correlation (ICC) coefficients for the test-retest procedure of 0.91 for the CHAQ, and 0.87 and 0.89 for the physical and psychosocial summary scores of CHQ, respectively. Agreement between parents and children evaluated for the CHAQ was high with an ICC of 0.89 for the disability index; weighted kappa coefficients for the 8 domains ranged from 0.61 to 0.72. Convergent validity was demonstrated by significant correlations with the JIA core set of variables (physician and parent global assessment, scores for active joints and joints with limited range of motion, erythrocyte sedimentation rate) for both instruments. Both CHAQ and CHQ discriminated between healthy and JIA children, but only the disease specific CHAQ questionnaire discriminated clearly between the 4 JIA subtypes. In conclusion, the French versions of the CHAQ and the CHQ are reliable, and valid health assessment questionnaires to be used in children suffering from JIA.

One of the strongest known association between human leukocyte antigen (HLA) phenotype and disease is that of ankylosing spondylitis and HLA-B27. Thus, the determination of HLA-B27 status is an useful tool in the diagnosis of ankylosing spondylitis. To date, the 2 reference methods for HLA typing (microlymphocytotoxicity and molecular biology techniques), are costly in terms of both technician time and materials, and require a great deal of experience. In total, these techniques are not well-suited for routine application in clinical immunology laboratories. Use of flow cytometry has recently been applied for HLA-B27 typing. Nevertheless, it requires an extensive validation protocol. We developed a flow cytometry technique as standardized as possible (whole blood, automated lysing system, automated photomultiplier voltage calibration, definition of thresholds stable with time) and validated our results by comparison with microlymphocytotoxicity. In total, 326 samples were analyzed. We found 99% of concordant results between the 2 techniques, and neither false positive results nor false negative results with flow cytometry could be observed. These results illustrate the reliability of the protocol. It should be remembered that reference technique remains necessary to confirm the few results (< 1%) found in "grey zone" by flow cytometry. Standardization of flow cytometry techniques, as described in this work for HLA B27, seems to be a reasonable goal for the next decade in clinical immunology laboratories.

Specific features of upper lumbar disk herniations are reviewed based on data from the literature and from a retrospective study of 24 cases treated surgically between 1982 and 1994 (seven at L1-L2 and 17 at L2-L3). Clinical manifestations are polymorphic, misleading (abdominogenital pain suggestive of a visceral or psychogenic condition, meralgia paresthetica, isolated sciatica; femoral neuralgia is uncommon) and sometimes severe (five cases of cauda equina syndrome in our study group). The diagnostic usefulness of imaging studies (radiography, myelography, computed tomography, magnetic resonance imaging) and results of surgery are discussed. The risk of misdiagnosis and the encouraging results of surgery are emphasized.

Objective: To test the effects of synovial fluids (SF) on human cartilage in an in vitro model., Methods: Freshly collected SF were incubated with cryostat sections of articular cartilage, and glycosaminoglycan (GAG) loss determined by microdensitometry after alcian blue staining., Results: Of 20 rheumatoid SF, 11 induced significant GAG loss compared with only 3 out of 15 osteoarthritic SF. The effect of rheumatoid fluids appeared to be related to disease activity. GAG loss was partially prevented by a broad spectrum serine protease inhibitor and a specific elastase inhibitor. Cartilage degrading activity was lost on storage which may explain why it has not been widely reported before., Conclusion: Rheumatoid SF can directly degrade cartilage through the action of proteases. There is an involvement of serine proteases, elastase in particular.

Objective: Rheumatoid arthritis is associated with a worse prognosis in females and is influenced by sex hormone changes. Similar observations in osteoarthritis support the hypothesis that gender differences in cartilage make a hitherto unrecognized contribution to gender differences in arthritis. The aim of the present study was to investigate potential gender differences in articular cartilage biochemistry, metabolism and response to inflammatory mediators., Methods: Femoral head cartilages from age-matched male and female Wistar rats were analysed for the water, glycosaminoglycan, hydroxyproline and collagen crosslink contents. Proteoglycan loss and synthesis were assessed in vitro, and in the presence and absence of serum and interleukin-1. An in vivo model of inflammation-induced cartilage degradation was employed to investigate gender differences in cartilage susceptibility to erosion caused by granulomatous tissue., Results: Articular cartilage from male Wistar rats presented higher levels of both proteoglycan and collagen and showed a lower spontaneous glycosaminoglycan loss and higher proteoglycan synthesis in vitro than cartilage from females. Proteoglycan synthesis from female, but not male, cartilage was significantly stimulated by foetal calf serum. Female cartilage was more sensitive to IL-1 inhibition of proteoglycan synthesis while the opposite was observed in IL-1-induced proteoglycan loss. Female cartilage was more susceptible to granuloma-induced degradation than male when implanted into female mice, but no differences were observed between male and female cartilage implanted in male mice., Conclusion: These results demonstrate important gender differences in cartilage biochemistry, metabolism and susceptibility to inflammatory mediators which may have important consequences for the joint destruction in arthritis and support a role for hormone therapy.

Objective: To investigate sex differences in granulomatous inflammation and its effects upon articular cartilage and to assess the potential role of sex steroids in the process., Methods: The cotton-pellet cartilage implant model was used with male and female mice in the presence and absence of gonadectomy and hormone replacement. The effects of granulomatous tissue upon articular cartilage was assessed and tissue content of interleukin 1 (IL-1) was determined. The expression of sex hormone receptors in inflammatory tissue was investigated by immunocytochemistry., Results: Female mice showed a higher ability than males to degrade cartilage irrespective of the sex of the cartilage implanted. Gonadectomy resulted in a significant acceleration of cartilage damage in both sexes, which was reverted by estrogen replacement in females and androgen replacement in males. Female granulomata had significantly higher IL-1 content than those from males. Gonadectomy was associated with an increased IL-1 content in males but not in females, the effects being abolished by androgen replacement in males. Estrogen and androgen receptors were identified in inflammatory cells from the granulomatous tissue., Conclusion: Our data demonstrate that sex hormones affect inflammation induced cartilage degradation in male and female mice probably through the modulation of cytokine production and release in the granulomatous tissue. Further investigation on the effects of sex steroids in inflammation induced cartilage degradation may help elucidate their pathogenic role and therapeutic potential in human disease.

The effects of three antiarrhythmic drugs were investigated in anesthetized, open-chest pigs, in a left ventricular area, under pacing at a constant high rate (180 beats/min), in the absence and presence of ischemia. Ischemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin. In addition to the surface electrocardiogram, conduction time and monophasic action potential were recorded in the contractile fibers. In the absence of ischemia, intravenous flecainide and propafenone 2.5 mg/kg, and intravenous cibenzoline 2.0 mg/kg considerably lengthened conduction time (by 50-90%) but had no significant effect on the monophasic action potential duration. Consequently, the cited antiarrhythmic drugs enhance the prolongation of conduction time by 60% but do not limit the 30% shortening of the monophasic action potential caused by ischemia. Contrary to what was expected, they largely reduced the time to onset of the fibrillation due to ischemia from about 120 to 25 seconds. Thus, they manifested profibrillatory properties (more pronounced than those of other antiarrhythmic drugs of class I), which might be explained by their potent action on depolarization.

The effects of the calcium channel modulators, Bay k 8644, infused i.v. at a rate of 2.5 micrograms/kg/min, and diltiazem, injected i.v. in a dose of 0.5 mg/kg, on the susceptibility to fibrillation induced by ischaemia, were investigated in anaesthetized, open-chest pigs. Ischaemia was produced, under ventricular pacing at constant high rate (180 beats/min), by transient complete occlusion of the left anterior descending coronary artery, near its origin. It was maintained till the triggering of fibrillation. The propensity to fibrillation was judged from the time elapsing between the onset of occlusion and the onset of fibrillation (time to fibrillation). In addition to the surface electrocardiogram, conduction time and monophasic action potential were recorded in the ventricular contractile fibres, as were dP/dtmax in the left ventricle and blood pressure in the carotid artery. At the end of a 10 min infusion, Bay k 8644 lowered to a large extent (about 40%) the time to fibrillation, which returned to its control values within the following 20 min. Conversely, diltiazem increased the time to fibrillation by a factor 4 or 5 at 5 min after its administration. This time to fibrillation remained substantially increased 25 min later. These changes were not associated with alterations in conduction time or monophasic action potential duration in the absence of ischaemia, but with significant alterations in myocardial contractility and blood pressure: in the direction of an increase with Bay k 8644 and of a decrease with diltiazem. These results are in agreement with the enhancement by Bay k 8644 and the prevention by diltiazem of cell calcium overload which is at present recognized as being the essential determinant of the fibrillatory process.

Kaposi's sarcoma appeared 8 months after the start of captopril treatment in a 70-year-old woman with rheumatoid arthritis. A marked reduction of cutaneous and gastric lesions occurred when captopril was stopped. These findings are compared to immunosuppressive drug induced forms of Kaposi's sarcoma.

The effects of three Ic antiarrhythmic drugs were investigated in anaesthetized, open-chest pigs, in a left ventricular area under pacing at constant high (180/min) rate, outside and during an ischaemia produced by temporary complete occlusion of the left anterior descending coronary artery, 1-1.5 cm from its origin. In addition to surface ECG, conduction time and monophasic action potential were recorded in the contractile fibres. Measurement of effective refractory period was added outside the periods of ischaemia. In this event, flecainide and propafenone, in 2.5 mg/kg dose, and cibenzoline, in 2.0 mg/kg dose, i.v. injected, lengthened considerably (50 to 90%) conduction time, but did not affect or hardly affected monophasic action potential and effective refractory period. During ischaemia, they did not hinder the abbreviation of monophasic action potential (30%) and reduced to a large extent (about 120 to 25 s) the onset time of fibrillation. The profibrillatory effect of Ic antiarrhythmic drugs, certainly more pronounced than those of other antiarrhythmic drugs, might be explained by their potent action on depolarization of the contractile fibres coincident with an almost total absence of action on repolarization.

Typical cauda equina syndrome secondary to long-standing ankylosing spondylitis is reported in a 63-year-old man. Radionuclide cisternography demonstrated a resorption defect of cerebrospinal fluid in the enlarged lumbosacral dural sac. After transient symptomatic improvement with acetazolamide, a lumboperitoneal shunt was placed. The rate of cerebrospinal fluid, isotope resorption became normal. In the 5 years of follow-up, partial remission has been observed.

The authors studied the special features of the vertebral location of this benign tumour of osteoblastic origin in eight cases of spinal osteoblastoma. Clinically, neurological complications are frequently present and scolioses may arise and persist after treatment; radiologically, new imaging techniques enable the limits of the tumour to be assessed with greater accuracy with respect to the neighbouring bone and their relationship to the components of the vertebral canal; surgically, there are difficulties specific to this location raised by the proximity of nervous components, and also by the vertebral destabilization entailed by the considerable bone involvement. Anatomicopathological diagnosis remains difficult, particularly in the case of osteoid osteoma.