[Prolongation of anti vitamin K treatment for 18 months versus placebo after 6 months treatment of a first episode of ideopathic pulmonary embolism: a mutlicentre, randomised double blind trail. The PADIS-EP Trial]. / Prolongation d'un traitement par antivitamine K pendant dix-huit mois versus placebo au décours d'un premier épisode d'embolie pulmonaire idiopathique traité six mois: un essai randomisé multicentrique en double aveugle. Essai "PADIS-EP".

BACKGROUND: After stopping a 3 to 6 months course of oral anticoagulation for a first episode of idiopathic venous thromboembolism (VTE), the risk of recurrent VTE is high (10% per year). In this setting, international guidelines recommend at least 6 months treatment. However, this recommendation is not satisfactory for the following reasons: (1) no randomized trial has compared 6 months to extended duration (2 years) anticoagulation; and (2), even though the frequency of recurrent VTE is similar after pulmonary embolism (PE) and deep vein thrombosis (DVT), the fatality rate of recurrent VTE after PE is higher than that after DVT. METHODS: A French multicentre double blind randomized trial. The main objective is to demonstrate, after a first episode of symptomatic idiopathic PE treated for 6 months using a vitamin K antagonist, that extended anticoagulation for 18 months (INR between 2 and 3) is associated with an increased benefit / risk ratio (recurrent VTE and severe anticoagulant-related bleeding) compared to placebo. The double blind evaluation is ensured using by active warfarin and placebo, and blinded INR. The protocol was approved by the ethics board of the Brest Hospital on the 7th of March 2006. For an alpha risk of 5% and a beta risk of 20%, the estimated sample size is 374 patients. EXPECTED RESULTS: This study has the potential to: (1) demonstrate that the benefit / risk ratio of extended anticoagulation for 18 months is higher than that observed with placebo in patients with a first episode of idiopathic PE initially treated for 6 months, during and after the treatment period; and (2) to validate or invalidate the contribution of isotope lung scans, lower limb Doppler ultrasound and D-Dimer at 6 months of treatment as predictors of recurrent VTE (medico-economic analysis included).

[Horton's disease in elderly patients aged over 75: clinical course, complications of corticotherapy. Comparative study of 164 patients. Towards a reduced initial dose]. / Maladie de Horton du sujet âgé de plus de 75 ans: particularites évolutives, complications de la corticothérapie. Etude comparative sur une série de 164 patients. Vers une dose d'attaque réduite.

PURPOSE: Our study compares clinical and therapeutic courses (corticosteroid response, corticosteroid amount, complications) in people with giant cell arteritis before and over 75 years, during the first year of treatment. METHODS: A series of 164 patients was retrospectively analysed (mean age: 73.3 years) among the two subgroups: before 75 and over 75 years. Patient received (monitoring of reduction in the corticosteroid dosage) a 240 mg intravenous bolus of methylprednisolone followed by 0.5 or 0.7 mg/kg/d of prednisone, or 0.7 mg/kg/d of prednisone without the bolus. RESULTS: Corticosteroid response was identical for the two groups, before and over 75 (patients with corticoresistance: 15% vs 11.4%; NS) and giant cell arteritis-related complications were equivalent (n = 2 vs n = 2; NS). Corticosteroid load was slightly lower in the elderly group (cumulative dose of corticosteroids during the first year of treatment 5.2 g vs 5.8 g; P = 0.03). Patients with rheumatic side effects (collapses of vertebral bodies, mainly) were more frequent in the elderly group (15.5% vs 4.3%; P = 0.01), in spite of a limited mean follow-up period (10.7 months). CONCLUSION: Even if steroid response was identical in the therapeutic course of giant cell arteritis, rheumatic side effects appeared more frequent in the elderly group (over 75 years). In order to obtain a corticosteroid-sparing effect, new studies are necessary to evaluate a reduced initial dosage of corticosteroids.

A randomized, multicenter, controlled trial using intravenous pulses of methylprednisolone in the initial treatment of simple forms of giant cell arteritis: a one year followup study of 164 patients.

OBJECTIVE: (1) To evaluate the corticosteroid sparing effect of an initial intravenous (i.v.) pulse of methylprednisolone (MP) in the treatment of simple forms of giant cell arteritis (GCA). (2) To analyze corticosteroid response, steroid related side effects, and GCA complications. METHODS: Patients received a 240 mg i.v. pulse of MP followed by 0.7 mg/kg/day oral prednisone (Group 1) or 0.7 mg/kg/day prednisone without an i.v. pulse (Group 2, controls), or a 240 mg i.v. pulse of MP followed by 0.5 mg/kg/day prednisone (Group 3). Corticosteroid dosage was reduced after normalization of 2 biological inflammatory variables to obtain half-dosage after 4 weeks in Groups 1 and 2 and 20 mg/day after 2 weeks in Group 3. Tapering was systematically attempted from the 6th month of treatment. RESULTS: One hundred sixty-four patients were included in the trial (1992-96). Cumulative doses of corticosteroids after one year were identical for all groups (p = 0.39). No significant differences were observed in the time required for normalization of C-reactive protein, corticosteroid resistance (13.5%), and corticosteroid related side effects (39% of patients; p = 0.37). Corticosteroid resistant patients received larger doses and showed a high risk of GCA related complications (p = 0.02). CONCLUSION: MP pulses have no significant longterm, corticosteroid sparing effects in the treatment of simple forms of GCA and should be limited to complicated forms. Moreover, corticosteroid resistance is a real risk factor for GCA complications.

[Extrapulmonary tuberculosis in the central western region. Retrospective study of 217 cases (Gericco 1991-1993)]. / Tuberculose extrapulmonaire dans la région centre-ouest. Etude rétrospective de 217 cas (Gericco 1991-1993).

OBJECTIVES: To analyze the epidemiological, clinical and diagnostic characteristics of extrapulmonary tuberculosis in western France observed from 1991 to 1993 in different patients populations (HIV+ infected patients, immunosuppressed non-HIV infected patients, non-immunosuppressed patients) and according to various localizations (lymph nodes, bone and joints, genital organs, nervous system and meninges, miliary disease). METHODS: This retrospective study included 217 cases of extrapulmonary tuberculosis diagnosed from 1991 to 1993 in western France by GERICCO (Groupe d'Epidémiologie et de Recherche en Infectiologie Clinique du Centre-Ouest). Demographic, clinical, biological, microbiological and radiographic characteristics as well as clinical course on specific therapy were assessed. RESULTS: Extrapulmonary tuberculosis generally occurred most often in immunosuppressed patients but 34% of cases were observed in people without any underlying disease or risk factors. Delay to diagnosis was especially long in the non-immunosuppressed patients (mean = 96 days) but shorter in the HIV-infected patients (mean = 59 days). It was shorter in case of nervous system involvement (mean = 52 days) or military disease (mean = 80 days) than in bone and joints (mean = 120 days) and lymph nodes (mean = 102 days). Microbiologically proven tuberculosis represented only 75% of cases despite numerous investigations. Overall prognosis was good except in nervous system and meninges localizations. Failures were mainly due to death in immunosuppressed patients. CONCLUSION: Extrapulmonary tuberculosis remains frequent even in patients lacking risk factors. In 50% of cases, confirmation of diagnosis takes more than one month. In case of doubt, clinicians should not wait for laboratory results before implementing empirical specific therapy.

[Multifocal tuberculosis. Apropos of 49 cases in the midwest region. GERICCO (Group for Epidemiology and Research in Clinical Infections of the Central West of France), 1991-1993]. / Tuberculose multifocale. A propos de 49 cas dans la région Centre-Ouest (Géricco, 1991-1993).

Diffuse or multifocal tuberculosis (TB) accounts for 9% to 10% of cases of extrapulmonary TB and carries a poor prognosis with a mortality rate of 16% to 25%. Forty-nine cases of multifocal TB defined as involvement of two extrapulmonary sites with or without pulmonary TB were reviewed. Mean patient age (+/- SD) was 50 +/- 18 years. Twenty-three per cent of patients were immigrants. A history of TB and contact with a TB patient were found in 23% and 18% of cases, respectively. Of the 52% of immunocompromised patients, 38% were HIV-positive. The skin tuberculin test was positive in 67% of cases. Mean time from symptom onset to admission was 80 +/- 77 days (median, 58 days). The 49 patients had a total of 128 TB foci. Six patients had positive blood cultures. The tubercle bacillus was recovered from the extrapulmonary sites in 88% of cases. Mean treatment duration was nine months. Recovery from the TB was achieved in 64% of cases. The overall mortality rate was 47%, and 33% of patients died as the direct result of TB. Most deaths occurred in immunocompromised patients. A high index of suspicion for multifocal TB should be maintained in immunocompromised patients, even those who test negative for the HIV.

Repair of a myelin lesion by Schwann cells transplanted in the adult mouse spinal cord.

In multiple sclerosis and experimental demyelination, oligodendrocytes and Schwann cells are able to repair myelin lesions of the central nervous system. However, spontaneous myelin repair is often insufficient. Several approaches to enhance remyelination have been considered and transplantation of myelin-forming cells has been proposed as one of them. In this paper, we present results which confirm the ability of transplanted Schwann cells to remyelinate an induced demyelinated lesion of the spinal cord. Schwann cells were either purified Schwann cells isolated from 1-2-day-old rat sciatic nerves, or immortalized Schwann cells (MSC80) arising from a purified culture of 7-day-old mouse sciatic nerves. They were transplanted into or at a distance from a lysolecithin-induced lesion of the Shiverer spinal cord. Labelling of the Schwann cells with the fluorochrome Hoechst 33342 enabled us to trace them after transplantation in their host and evaluate their ability to reach and to repair the demyelinated lesion. Using the Hoechst-Shiverer model, we show that when transplanted in the lesion, cultured Schwann cells, even immortalized, are able to remyelinate such a lesion efficiently. In addition, when transplanted at a distance from the lesion, they are able to reach and repair the lesion in time frames which allow them to compete actively with host oligodendrocytes.

The fate of Schwann cells transplanted in the brain during development.

Purified rat Schwann cells labeled with Hoechst 33342 fluorescent fluorochrome were transplanted into the brain of the newborn shiverer mouse. The grafted cells survived and were able to migrate through the host parenchyma. However, Schwann cell migration was restricted to the grafted hemisphere and to structures adjacent to the graft. With time, Hoechst labeled cells, present at the site of implantation or dispersed in the host parenchyma, decreased progressively in number. Instead, they concentrated along the blood vessels, meninges and ventricles. Despite the presence of Hoechst labeled Schwann cells in white matter tracks during the process of central myelination, Schwann cell myelination could not be evidenced by immunodetection of the peripheral myelin protein or by ultrastructural observation of the typical Schwann cell basement membrane surrounding peripheral myelin. A series of additional transplantations involving Schwann cells of mouse or rat origin, grafted either as cell suspensions or as nerve fragments, demonstrated that transplanted Schwann cells formed myelin around developing host axons only when included in a nerve fragment. Immunodetection of GFAP in astrocytes and type IV collagen in basement membranes as well as electron microscopy showed that reactive astrocytes invaded the grafted area after the first week of transplantation and sometimes formed basement membranes isolating partially the graft from the host parenchyma. During host myelination, astrocytes, which were present in most white matter structures, surrounded grafted cells. Occasionally, they enclosed Schwann cells in basement membranes or encircled host axons. Later, reactive astrocytes were associated with Schwann cells restricted to blood vessel and ventricular walls, and meninges. Our results suggest that in the presence of competitive developing oligodendrocytes, astrocytes are able to limit migration and prevent myelination of Schwann cells transplanted in the newborn shiverer brain. In addition, astrocytes seem to be able to expel the grafted cells and finally exclude them from the host parenchyma.

[Massive medullary forms of Hodgkin's disease and acute myelofibrosis (author's transl)]. / Formes médullaires massives de la maladie de Hodgkin et myélofibroses aiguës.

Ten cases of Hodgkin's disease was massive bone marrow invasion. This particular form of the disease is seen either at the outset or in Stage IIIB with a rapid course. It is reflected by a pancytopaenia with poor marrow with little or no superficial nodes. These very atypical forms of Hodgkin's disease must thus always be considered as a possibility in the context of acute malignant myelofibrosis. They indicate a special and unexplained behaviour of the host to the Hodgkin's tumour.