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Zolpidem belongs to a new class of hypnotic agents, chemically distinct from the pre-existing ones, and has a unique neuropharmacological profile. It induces sedative/hypnotic effects in rodents at doses much lower than those for anticonvulsant and myorelaxant activities. Clinically, zolpidem is indicated for the short term treatment of insomnia. It has a short half-life (2.4 h), with no active metabolite, and does not accumulate during repeated administration. The pharmacokinetic profile associated with the absence of active metabolites is consistent with the short duration of action and absence of residual effects that have been observed. Polysomnographic experience indicates that zolpidem induces a sleep pattern which is similar to that of physiological sleep, and which produces either no or only minimal effects on sleep architecture after abrupt discontinuation. Aspects of the general safety of zolpidem have been studied in data obtained from healthy volunteers and patients, both adult and elderly, during its clinical development and in post-marketing experience. Zolpidem appears to be well-tolerated in adults and in the elderly, when administered in accordance with prescribing instructions. The available data indicate that, in these circumstances, the risk of abuse or dependence is minimal.

L'efficacite de la prevention d'un risque medicamenteux depend de la precision avec laquelle ses facteurs declenchants ou favorisants sont connus et de la qualite de l'information donnee a son sujet aux prescripteurs et aux utilisateurs. L'identification d'un risque devrait mettre a profit l'ensemble des donnees precliniques et cliniques disponibles pour la specialite pharmaceutique consideree et les confronter aux donnees existantes pour des medicaments partageant un meme mode d'action ou une meme strategie therapeutique. L'information doit s'appuyer sur un plan de communication adapte au contexte de la pathologie traitee, des alternatives therapeutiques existantes et du benefice attendu.

Effective prevention of drug-induced risks depends on an accurate understanding of their triggering or predisposing factors, and the quality of information on these available to prescribing practitioners and users. All preclinical and clinical data available on the proprietary medicinal product concerned should facilitate identification of a risk, and these data should be compared with existing data on drugs sharing the same mode of action or therapeutic strategy. This information should be based on a communication plan adapted to the context of the disease under treatment, the therapeutic alternatives available and the benefits expected.

The development of a drug for the fundamental treatment of osteoarthritis requires that its efficacy should be proven clinically. This implies that there must be a clear definition of the evaluation criterion (slowing down in the progression of osteoarthritic lesions). Marketing of a drug depends on the efficacy/safety relationship, but any assessment of the value of a fundamental treatment for osteoarthritis goes beyond the framework of a study of its efficacy. Its usefulness can be measured in terms of scales estimating the quality of life that are related to the osteoarthritic disease. Overall criteria, such as the level of maintenance treatment, can be used in comparative, randomized, double blinds trials. Pragmatic trials seem to afford a methodology which is suited to the evaluation of usefulness and therapeutic benefit. The basis of cost/effectiveness, cost/usefulness and cost/benefit studies relies on a comparison of the cost of osteoarthritis and its treatment with the benefits brought about by such treatment.

The authors made a comparative study of the effectiveness and tolerance of D-penicillamine (DP) and pyrithioxine (Pyr) and investigated possible prognostic factors for the tolerance and effectiveness of these two treatments. This retrospective study concerned 150 patients with rheumatoid arthritis (RA). 86 patients were treated with DP and 64 were treated with Pyr. The percentage effectiveness, evaluated in terms of morning stiffness and the articular index as well as the need for steroidal and non-steroidal anti-inflammatory agents, attained 67.4 p. cent with DP and 51.6 p. cent with Pyr. Suspension of treatment because of ineffectiveness, was more frequent with Pyr. The changes in the following laboratory parameters were also compared: ESR, rheumatoid serology, ANF, C3 and C4 complement levels, IgG, IgA and IgM levels. The treatment was stopped definitively because of intolerance in 37.2 p. cent of cases with DP and in 29.7 p. cent of cases with Pyr. Serious renal and haematological complications are essentially, but not exclusively, due to DP.

Two cases of classical rheumatoid arthritis complicated by the development of a glomerulopathy independently of drug treatment are presented. Renal biopsy showed membranous glomerulonephritis in one case and fusion of foot processes in the second. The literature is reviewed and the possible relationships between rheumatoid arthritis and these glomerulopathies are discussed. The authors conclude to the absence of causal relationship between these two diseases.

The authors discuss current pharmacological knowledge of D-Penicillamine (DP) in man and its possible mechanism in the treatment of rheumatoid polyarthritis. Dosage by liquid phase chromatography enables study of intestinal absorption, reduced by meals, the distribution made according to a 2 compartment model, urinary and faecal excretion. Metabolism occurs mainly by oxidation of free D-Penicillamine. 20 percent of the plasmatic DP, not bound to proteins, appears in the form of disulphides and free DP. The only known metabolite is S-methyl DP, produced in small amounts. The DP mechanism remains hypothetical. The authors discuss its effects on the metabolism of copper and zinc, dismutatic super-oxide activity, the radical thiol level, collagen metabolism, cartilaginous destruction, prostaglandin synthesis, polynuclear chemotaxis and the immuno-system.

The authors report a follow-up study of 24 patients who initially fulfilled ARA criteria for juvenile chronic arthritis (JCA). After an evolution period of 6 to 50 years, diagnosis was revised in three patients: one suffered from mixed connective tissue disease, another from psoriatic arthropathy and the last one from Crohn's disease. Among the 21 remaining JCA patients, 16 had still an inflammatory disease when last examined and 2 of these 16 died from amyloidosis. The articular involvement appears to be similar in systemic and polyarticular disease. The physical disability can be correctly appreciated only after a 10 years evolution period. Six patients were functionally classed in grade 4. Their loss of motility was due to hip or/and knee involvement. Five of them improved after complex orthopaedic surgery and the last could not undergo anaesthesia. Both articular involvement and the fact of the chronicity of illness account for psychological and social inaptitudes. Different therapeutics are appreciated and compared.

One case of Sharp's syndrome (mixed connective tissue disease) is reported After 11 years without treatment the long-term benign evolution is affirmed. The clinical and biological signs leading to this diagnosis are reviewed and discussed.

Several recent reports emphasize the adverse effects of non-steroidal antiinflammatory drugs on renal function. These reports incriminate several phenylpropionates but none involve ketoprofen. There have been no indications that clometacin has renal toxicity. We report a case of acute renal failure which occurred during therapy with both ketoprofen and clometacin. The onset of renal failure after their administration, the return to normal renal function once therapy was discontinued and the absence of any other detectable etiology make the responsibility of the treatment very likely. The different possible mechanisms and the role of underlying disease and of associated therapy are discussed. In the index case the reduced excretion of urinary prostaglandin E2 suggests inhibition of prostaglandin synthesis rather than direct drug toxicity or an immuno-allergic mechanism.

Eighty four patients with classical rheumatoid arthritis were treated with 300-1 200 mg/day of D-Penicillamine. During follow-up, attention was paid to various clinical and biological parameters including the antinuclear factor (ANF) and anti-deoxyribonucleic acid (DNA) antibodies. Before therapy the ANF was greater than or equal to 1/50 in 22 patients (26 p. 100); it increased significantly in treated patients (p less than or equal to 0.01). In addition, positive ANF were found in 22 of the 62 patients (35.5 p. 100) who had negative ANF before D-Penicillamine therapy. There was no correlation between the appearance of ANF or the increase in ANF levels and the initial clinical and biological status, tolerance of therapy, the percentage of cases in which D-Penicillamine was effective. Anti-DNA antibodies were found in 5 patients but no clinical signs of lupus disease were observed despite treatment periods of up to 3.5 years in one case. Anti-SM antibodies were also found in one female patient. The disappearance of anti-DNA antibodies after reducing the dosage of D-Penicillamine (1 case) or withdrawal of therapy (2 cases) is an argument in favour of the inducing role of the drug. The incidence, signification and consequences of these observations are analysed and compared with previously reported results.

We studied circulating immune complexes using a test involving the precipitation of these complexes with polyethylene glycol 6000 at 2.5 percent, and characterization of the Clq bound in vivo to immunoglobulins in the serum of 126 healthy subjects, 95 hospitalized controls and 181 patients suffering from rheumatoid arthritis (RP). Likewise, the RP benefited from a study of cryoglobulins (CG). The PEG-Clq proved positive (PEG +) in 7 per cent of the healthy controls, 25 per cent in the seronegative RP. ThePEGRP have a level of proteins, gammaglobulins, IgM and IgG that is higher than in patients in whom the test is negative. On the other hand, they have a lower level of C4. One CG was detected in 43 patients who were all PEG +. The level of CG is proportionate to the intensity of the articular inflammation, the sedimentation rate, the level of seric iron and that of hemoglobin. The composition of the precipitins obtained by activity of the PEG is very close to that of the CG.

The authors report a case of Sjögren's syndrome associated with Raynaud phenomenon and mixed IgM-IgG cryoglobulinaemia. Three years after the onset of this association:--Immunoelectrophoresis of the serum showed a monoclonal IgM (lambda) protein, --the level of the mixed IgM-IgG cryoglobulinaemia had increased from 28 mcg/ml up to 12 mg/ml and its IgM component was monoclonal (lambda) with anti-IgG activity. Search for amyloïdosis and for a malignant lymphoma was negative. Such an association of a benign monoclonal gammopathy, mixed cryoglobulinaemia and Sjögren's Syndrome has only exceptionally been reported in the literature.

The authors report the case of a 14 year-old adolescent girl presenting with rickets due to vitamin D deficiency. This rare condition has already been described in young immigrants coming from Asia and North Africa. Most often, symptoms consist of diffuse pains, with radiologic signs of skeletal demineralization and/or signs of bone resorption. Evolution is favourable under vitamin treatment. This condition seems to be induced by an increased requirement for vitamin D at time of adolescent growth spurt. It is promoted by the lack of sunlight and the skin pigmentation. It is likely that a number of these deficiencies are undiagnosed and recover spontaneously.

Two cases of Henoch-Schönlein purpura in adults are reported. Both patients presented with severe digestive symptoms suggesting malabsorption or exudative enteropathy. Roentgenological examinations showed marked anomalies of the small intestine as well as changes suggestive in intra-mural hematoma located in the stomach in one case and in the duodenum in the other. Hypoalbuminemia occurred in both patients during the course of the disease and was highly suggestive of protein-loosing enteropathy. Disseminated intravascular coagulation was seen in one patient. Both patients recovered from their gastrointestinal disease. Roentgenologic changes disappeared in one case; in the other, marked compression and distension of the duodenum were still visible six months after onset.

Analysis of cervical spine involvement is based on data from 29 cases of juvenile chronic arthritis (JCA), (8 systemic and 21 polyarticular forms). Follow-up is a least 5 years and exceeds 10 years in 17 cases. Among these 29 patients, 14 experienced cervical pain. One patient had Arnold neuralgia. No other neurologic complications were recorded. 14 of the 29 patients exhibited one or more roentgenological changes (3 of the 8 systemic patients and 11 of the 21 polyarticular patients). Of these, 4 never had any corresponding clinical symptoms. A chronologic correlation between onset of clinical and radiological signs was clearly established in only three cases. Among roentgenologic features, loss of physiologic lordosis was recorded in four patients. This finding was always associated with other radiologic changes. Seven patients had involvement of the posterior spine: blurred articular outlines and erosion of posterior epiphyses in one patient, fusion of neural arch joints involving C2-C3 in two patients and C2-C3 and C3-C4 in two others, and extensive fusion from C2 to C7 in two cases. Changes in the anterior spine were always accompanied with posterior lesions at the same level. Atlanto-axial or atlanto-occipital involvement was found in 9 of our 29 patients. Seven had forward slipping of C1 over C2. No instances of vertebral slipping below C1-C2 or of vertebral collapse were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

The inhibitory effects of acute pain produced by the Lasegue's manoeuvre on the lower limb nociceptive flexion reflexes induced by electrical sural nerve stimulation were explored in patients complaining of sciatica as a result of an identified unilateral disc protrusion. Lassegue's manoeuvre on the affected side produced a typical radicular pain and resulted in a powerful depression of nociceptive reflexes elicited either in the normal or in the affected lower limb. Simultaneously, patients reported relief of the electrically-induced pain. In contrast, painless Lasegue's manoeuvre on the normal side had no effect on these parameters.