Étude comparative de l’efficacité et de la tolérance de l’étidronate et de l’alendronate au cours de l’ostéoporose postménopausique. Influence de l’adjonction d’un traitement hormonal substitutif

Objectives. To compare the efficacy and safety of etidronate and alendronate in patients with postmenopausal osteoporosis and to assess the efficacy of either bisphosphonate in combination with hormone replacement therapy (HRT). Patients and methods. In this pragmatic study, the main efficacy criterion was the mean annual change in bone mineral density (BMD). Patients who had a past or current history of etidronate or alendronate treatment for postmenopausal osteoporosis with at least 18 months follow-up and an evaluation in 1999 were eligible. Recruitment was in an outpatient clinic with a special focus on metabolic bone diseases. Osteoporosis was defined as at least one low-energy fracture or as a lumbar spine or femoral neck BMD decrease to at least 2.5 SD below the mean in young women. HRT was not an exclusion criterion provided treatment duration was longer than one year. Etidronate was given cyclically (14-day courses in a dosage of 400 mg/d separated by 76-day intervals with calcium and vitamin D supplementation) and alendronate was given daily in a dosage of 10 mg/day. Results. Of the 99 patients who met our inclusion criteria, 53 received etidronate (including 23 on HRT) and 46 alendronate (18 on HRT). Repeat BMD measurements were obtained in 88 patients, including 11 who stopped their bisphosphonate therapy within the first year of use because of adverse events. Lumbar spine BMD (mean ±SD) increased significantly both in the etidronate group (+2.1%±0.7%/year) and in the alendronate group (+5.3%±0.9%/year). The increase was significantly greater with alendronate (P<0.01). The lumbar spine BMD increase was largest in the patients on alendronate and HRT (+6.5%±1.4%/year) and was smallest (and nonsignificant) in the patients on etidronate without HRT (+1.2%±0.8%). Femoral neck BMD showed no significant changes in any group. In the intention-to-treat analysis, fractures occurred in 12 etidronate patients (22.6%) and six (13.0%) alendronate patients (nonsignificant). Adverse events requiring bisphosphonate discontinuation before the scheduled date of the follow-up BMD measurement occurred in one patient (1.9%) in the etidronate group (generalized osteomalacia) and in ten patients (21.7%) in the alendronate group (upper or lower gastrointestinal tract symptoms in six and four patients, respectively; P<0.01). Conclusion. Both etidronate and alendronate significantly increased lumbar BMD, but the effect was significantly more marked with alendronate. Conversely, adverse effects, most notably gastrointestinal symptoms, were more common with alendronate, so that premature treatment discontinuation because of adverse events were more common in the alendronate group. Both differences should be taken into account when selecting the best drug for a patient with postmenopausal osteoporosis.     

Syndromes hémolytiques et urémiques de l’adulte

Hemolytic uremic syndrome (HUS) is related to a renal thrombotic microangiopathy, inducing hypertension and acute renal failure (ARF). Its pathogenesis involves an activation/lesion of microvascular endothelial cells, mainly in the renal vasculature, secondary to bacterial toxins, drugs, or autoantibodies. An overactivation of the complement alternate pathway secondary to a heterozygote deficiency of regulatory proteins (factor H, factor I or MCP) or to an activating mutation of factor B or C3 can also result in HUS. Less frequently, renal microthrombi are due to an acquired or a constitutional deficiency in ADAMTS-13, the protease cleaving von Wilebrand factor. Hemolytic anemia with schistocytes, thrombocytopenia without evidence of disseminated intravascular coagulation, and renal failure are consistently found. In typical HUS, a prodromal diarrhea, with blood in the stools, is observed, related to pathogenic enterobacteria, most frequently E. Coli O157:H7. HUS may also occur in the post partum period, and is then related to a factor H or factor I deficiency. HUS may also occur after various treatments such as mitomycin C, gemcitabine, ciclosporin A, or tacrolimus, and as reported more recently bevacizumab, an anti VEGF antibody. Atypical HUS are not associated with diarrhea, may be sporadic or familial, and can be related to an overactivation of the complement alternate pathway. More recently, some of them have been related to a mutation of thrombomodulin, which also regulates the alternate pathway of complement. In adults, several HUS are encountered in the course of chronic nephropathies: nephroangiosclerosis, chronic glomerulonephritis, post irradiation nephropathy, scleroderma, disseminated lupus erythematosus, antiphospholipid syndrome. Overall the prognosis of HUS has improved, with a patient survival greater than 85% at 1 year. Chronic renal failure is observed as a sequella in 20 to 65% of the cases. Plasma infusions and plasma exchanges are effective in most of the cases to treat hemolysis and thrombocytopenia. Steroid therapy is debated, as well as immunosuppressive drugs, including rituximab, in autoimmune forms. A new monoclonal anti-C5 antibody is tested, and seems to be effective in atypical HUS with abnormal complement alternate pathway activation. If terminal renal failure occurs, renal transplantation can be performed but the risk of recurrence, which very low in post infectious forms of HUS, is about 70 to 80% in genetic forms of complement regulatory protein deficiency.     

Les traumatismes de l’appareil génito-urinaire: Aspects épidémiologiques et lésionnels

Objectives

To analyze the frequency and the etiology of trauma to the genito-urinary tract as well as the types of lesions encountered.

Patients and Methods

This is a retrospective study carried out on 38 patients with genito-urinary trauma seen at Cocody University Hospital, Abidjan, Ivory Coast, between April 2000 and December 2006. The parameters studied were: age, sex, profession, etiology of the trauma, the type of lesions observed and their surgical management.

Results

Out of 16,425 trauma patients, 38 (0.2%) had genito-urinary lesions. Thirty-seven of them were males and one female with a mean age of 26.9 (range 5 to 63) years. The majority of the patients were victims of car accidents (42.1%, 16 cases), while 29% (11 cases) had a work accident, and 23.7% (9 cases) were victims of civil violence (physical assaults). In 81.6% of the cases, the urethra and the bladder were affected, while renal lesions and trauma to the external genital organs were found in 7.9% and 10.5% of the cases, respectively. Twenty-five patients (65.8%) had associated pelvic fracture. The trauma was direct in all patients with blunt trauma in 29 (76.3%) and penetrating trauma in 9 (23.7%). Surgical management consisted of end-to-end urethrorrhapy in the majority of patients (52.6%).

Conclusion

Genito-urinary trauma is rare and is more likely to affect young men. It is primarily caused by car and work accidents. Such trauma is usually associated with serious lesions.     

Rôle de l’ostéoprotégérine dans l’inflammation et la polyarthrite rhumatoïde

Osteoprotegerin (OPG), a member of the TNF-receptor family expressed by osteoblasts, has documented effects on the regulation of bone metabolism. OPG inhibits bone resorption and binds with strong affinity to its ligand RANKL, thereby preventing RANKL from binding to its receptor RANK. This system is regulated by calcium-modifying hormones. OPG may also be pivotal in modulating the immune system. RANKL-deficient mice exhibit both severe immunological abnormalities and osteopetrosis, and activated T cells express RANKL mRNA. RANKL secretion by activated T cells may induce osteoclastogenesis via a mechanism enhanced by several cytokines (TNF-α, IL-1, and IL-17) that promote both inflammation and bone resorption. Conversely, this mechanism is inhibited by OPG, IL-4, and IL-10, which have antiinflammatory effects and inhibit osteoclast formation. Activated T cells in the rheumatoid synovium express RANKL. Synoviocytes can differentiate to osteoclast-like cells under specific conditions, particularly when they are cultured with M-CSF and RANKL. Thus, the bony erosions seen in RA may result from RANKL/RANK system activation by activated T cells. This raises the possibility that OPG therapy to block this mechanism might prove beneficial in patients with RA.     

Bases physiques de l’élastographie et applications au tendon calcanéen normal et pathologique

Elastosonography is an evolution of ultrasound that maps the biomechanical and elastic properties of tissues by measuring their stiffness. Over the past five years, the number of studies on elastosonography in tendon pathologies raised. Indeed, this technique is promising, but how can radiologists use it in daily practice? The purpose of this review article is to summarize the data available to date about elastosonography focused on the calcaneal tendon in order to provide physicians with an overview that may help them understand and use elastosonography routinely. The physical principles of elastosonography are described. The aspects of normal, physiological and pathologic calcaneal tendon are discussed. Transient Shear Wave Elastography (SWE), which is the most recent elastosonographic technique, allowed to quantify tendon stiffening when tendon stress increases, confirmed tendon softening in case of tendinopathy, and shown tendon strength loss when calcaneal tendon is completely ruptured. SWE is still a wide research field on viscoelastic properties of normal, pathologic, aging and operated calcaneal tendon.     

Divergences (et convergences) de perceptions entre patients et néphrologues de l’impact de l’insuffisance rénale chronique non terminale sur l’élan vital en France : résultats de l’enquête MAEVA

RationaleThe impact of chronic kidney disease (CKD) on vital impetus is poorly documented in patients not undergoing renal dialysis and discrepancies can be observed between patients and physicians in perception of QoL and impact of the disease.MethodsA self-questionnaire was sent to 1282 French nephrologists and a mirrored self-questionnaire was given to patients (CKD stage 3, 4 or 5) by their nephrologist. Data were collected prospectively and anonymously.ResultsA total of 261 nephrologists and 172 patients participated in the survey. Sixty-six percent of patients reported a negative impact of the disease on their quality of life, which is also identified by nephrologists: important impact 22% vs 27%, mild or inconstant 44% vs 47%, mild or absent 34% vs 31% in patients and nephrologists, respectively. They had different perceptions about factors contributing to vital force; in particular, nephrologists underestimated their key role in psychological support. Indeed, the optimism and encouragements of nephrologists were considered to be a key factor of vital force for 60% of patients vs 20% of nephrologists (P < 0,001). During consultations, nephrologists were primarily focused on biological abnormalities and adherence to treatment while mood or sexual disorders were rarely investigated. The main objective of treatment was to maintain a normal life for patients and to delay dialysis for nephrologists.ConclusionNephrologists have a relative knowledge of CKD impact on the vital impetus of patients, but there are differences of perception. It could be improved through specific trainings.     

Le polytraumatisé et les anomalies de l’hémostase

Objective

Polytraumatized patients present with defects of haemostasis that manifest clinically either by haemorrhage and/or thrombosis. During the initial, as well as during the later phases of treatment, clinicians should take into account the most recent developments in the understanding, in the evaluation of the risk, and in the prevention of haemorrhagic and thrombotic complications.

Source

A group of experts, convened by the “Groupe d’intérêt en hémostase périopératoire” (Perioperative Haemostasis Interest Group) during the Annual Meeting of the Association of Anaesthetists of Quebec, held a symposium to review and integrate recent developments on haemostatic complications associated with trauma.

Main findings

The normal haemostatic balance is strongly compromised by trauma and shock. The percentage of patients with a coagulopathy and surgically uncontrollable haemorrhage varies between 18 and 40%. Abnormal coagulation after trauma is of multifactorial origin. Coagulopathy secondary to haemodilution is no longer considered the main cause of haemorrhage. Disseminated intravascular coagulation (DIC) is often manifest in the traumatic context. One out of every three polytraumatized patient will develop a deep vein thrombosis despite the preventive measures available at present. Clinical or laboratory detection of venous thrombosis either lacks sensitivity (physical examination or ultrasonography), or cannot be performed serially (phlebography).

Conclusions

Prevention and treatment of disorders of haemostasis relies upon the rapid and effective treatment of shock associated with trauma. Prevention of thromboembolic complications is paramount, taking into account the evolving balance between the risk of haemorrhage and the risk of thrombosis.     

Anatomie et imagerie de l’articulation tarsométatarsienne (articulation de Lisfranc)

The tarsometatarsal joint (Lisfranc joint) is a synovial articulation of plane variety that is made up of three compartments. It is located between the bases of the five metatarsals and the anterior tarsal bones (medial, intermediate, lateral cuneiforms and cuboid bones). A great stability is provided by the particular shape of the joint compared to a mortise created by the cuneiform bones and the base of the second metacarpal, sometimes referred to as the “keystone concept?? as well as strong dorsal, plantar and interosseous ligaments, including mainly the first medial cuneometatarsal interosseous ligament (Lisfranc ligament). Traumatic lesions are the commonest disorders of this joint. Violent accidents including a mechanism of forced plantar flexion combined with rotation are the main causes of injury. Imaging of the tarsometatarsal joint includes conventional radiographs, computed tomography (CT) and magnetic resonance imaging (MR). Conventional radiographic projections remain the first-line imaging modality. However, owing to their often subtle radiographic presentation, Lisfranc lesions are frequently overlooked. Due to its excellent spatial resolution and three-dimensional imaging capabilities, CT is the procedure of choice for the evaluation of the injured foot. MR may be more accurate at detecting ligamentous and synovial disorders particularly owing to its high density resolution.     

Douleurs céphaliques néoplasiques contrôlées par administration intraventriculaire de morphine et de clonidine

A 47-year-old woman suffered from a pharyngeal cancer causing pain only poorly relieved by high doses of oral morphine. Oral administration was switched to the intracerebroventricular (ICV) route but pain relief was only transient despite a daily dosage up to 1.5 mg of morphine. Finally an effective pain relief was achieved with increasing doses of clonidine (5 to 30 μg) in combination with morphine (1.5 mg) by ICV route. Neither arterial hypotension nor sedation occurred and the patient recovered transiently a better quality of Iife.     

Saga de la découverte de l’IL-1 et du TNF et de leurs inhibiteurs spécifiques dans la pathogénie et dans le traitement de la polyarthrite rhumatoïde

In the seventies, the molecule subsequently termed IL-1 was among the first cytokines to attract the attention of rheumatologists due to its biological role in tissue destruction and bone resorption. In the mid-eighties, cachectin/tumor necrosis factor was found to share some of these biological activities, and a strong synergism between the two cytokines became evident. While IL-1 appeared to be more important at the local level, TNF played a more prominent part at the systemic level. In 1984, we became aware of the existence of an antagonist to IL-1 - subsequently termed IL-1Ra (interleukin-1 receptor antagonist) - in urine of febrile patients; its mechanism of action was elucidated in 1987 and the molecule cloned in 1990. The natural inhibitors of TNF were identified in 1996/97 by different investigators and proved to be soluble fragments of the TNF receptor. A concept, commonly accepted at present, is that disease activity and clinical outcome are controlled by the balance between agonistic and antagonistic cytokines, and at present the principal goal is to understand the underlying mechanisms. This concept is illustrated by observations in numerous animal models. The control of IL-1 and TNF is strongly dependent on the contact between activated lymphocytes and monocytes, the main source of these cytokines. Inhibiting this interaction by interfering with ligand and counter-ligand may be a useful approach if it is possible to maintain the production of the cytokine antagonist. Apolipoproteins A-I and A-II as well as β2-integrins are molecules that block ligand/counterligand interaction. According to animal experiments and clinical data, blocking either IL-1 or TNF, or both, is beneficial. However, to determine not only the benefit but also the side effects of combination therapy in the human system, long-term clinical trials will be required.     

Comparaison de l'échographie et de l'imagerie par résonance magnétique pour l’évaluation de l’atteinte du genou dans les arthrites juvéniles idiopathiques

Objective. To examine the role of ultrasound versus MRI in assessing joint inflammation in patients with juvenile idiopathic arthritis (JIA) of the knee. Patients and methods. This study was conducted on 38 patients with juvenile idiopathic arthritis (25 girls and 13 boys), their ages ranged between 2-17 years (mean 8 years), presenting with joint swelling, tenderness, pain on motion and/or limitation of movement. Plain radiography, high resolution ultrasound and MRI examination of the knee (before and after contrast administration) were made to all patients. A control group of 10 subjects were also examined. Results. Compared to the control group, sonographic examination was found to be of great value as regards the joint effusion, popliteal cysts, lymph nodes and to a less extent,  the degree of affection of the articular cartilage. MRI was superior in evaluating the extent of synovial proliferation (pannus), thinning out and erosions of articular cartilage, loculated effusions as well as hypoplastic menisci and ligaments especially after contrast enhancement. Conclusion. Ultrasound is a simple, inexpensive and valuable tool in evaluating the initial stages of JIA. In more advanced stages of JIA and also for monitoring the progression of the disease process and response to therapy, MRI examination following gadolinium proved to be superior in evaluation of the joint affection.