Search

Introduction: Colchicine is a narrow therapeutic margin drug that does not have the adverse effects of corticosteroids and immunosuppressants. Its use in non-severe ocular inflammatory disease excluding Behcet's disease has not been studied., Methods: We included patients seen in the internal medicine department of Dijon University Hospital consecutively between September 2020 and September 2021 if they had received colchicine during their pathology. Patients with suspected Behçet's disease were excluded. Treatment efficacy was studied in patients with at least one year of disease progression who had received more than one year of colchicine. Successful treatment was defined as a 50 % reduction in the number of annual relapses on colchicine., Results: Sixteen patients were included (9 women and 7 men). They had recurrent anterior uveitis (n=10), recurrent scleritis (n=5) and intermediate uveitis. Opthalmological involvement was neither severe nor complicated. All patients combined, the annual relapse ratio (ARR) decreased from 1.8 (0.8-3.5) to 0.3 (0-1.6), (P=0.06). Colchicine was considered effective in three of 10 analyzable patients. In only one patient, treatment was stopped for adverse effects after six weeks., Conclusion: In view of the interesting benefit-risk ratio of colchicine, it seems appropriate to focus on this molecule in non-granulomatous anterior uveitis and non-severe recurrent scleritis., (Copyright © 2022 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To analyze the factors associated with response (control of ocular inflammation and corticosteroid-sparing effect) to biologics (anti-tumor necrosis factor [TNF]-α agents and tocilizumab) in patients with refractory uveitic macular edema (ME)., Design: Multicenter, retrospective, observational study., Participants: Adult patients with uveitic ME refractory to systemic corticosteroids, disease-modifying antirheumatic drugs, or both., Methods: Patients received anti-TNF-α agents (infliximab 5 mg/kg at week 0, 2, 6, and every 4-6 weeks [n = 69] and adalimumab 40 mg/2 weeks [n = 80]) and tocilizumab (8 mg/kg every 4 weeks intravenously [n = 39] and 162 mg/week subcutaneously [n = 16])., Main Outcome Measures: Analysis of complete and partial response rates, relapse rate, low vision (visual acuity in at least 1 eye of ≥ 1 logarithm of the minimum angle of resolution), corticosteroid-sparing effect, and adverse events at 6 months., Results: Two hundred four patients (median age, 40 years [interquartile range, 28-58 years]; 42.2% men) were included. Main causes of uveitis included Behçet's disease (17.2%), birdshot chorioretinopathy (11.3%), and sarcoidosis (7.4%). The overall response rate at 6 months was 46.2% (21.8% of complete response) with anti-TNF-α agents and 58.5% (35.8% of complete response) with tocilizumab. In multivariate analysis, treatment with tocilizumab (odds ratio, 2.10; 95% confidence interval [CI], 1.06-4.06; P = 0.03) was associated independently with complete response of uveitic ME compared with anti-TNF-α agents. Anti-TNF-α agents and tocilizumab did not differ significantly in terms of relapse rate (hazard ratio, 1.00; 95% CI, 0.31-3.18; P = 0.99) or occurrence of low vision (odds ratio, 1.02; 95% CI, 0.51-2.07; P = 0.95) or corticosteroid-sparing effect (P = 0.29). Adverse events were reported in 20.6% of patients, including serious adverse events reported in 10.8% of patients., Conclusions: Tocilizumab seems to improve complete response of uveitic ME compared with anti-TNF-α agents., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Traumatic experiences, such as conditioned threat, are coded as enduring memories that are frequently subject to generalization, which is characterized by (re-) expression of fear in safe environments. However, the neurobiological mechanisms underlying threat generalization after a traumatic experience and the role of stress hormones in this process remain poorly understood., Methods: We examined the influence of glucocorticoid hormones on the strength and specificity of conditioned fear memory at the level of sparsely distributed dentate gyrus (DG) engram cells in male mice., Results: We found that elevating glucocorticoid hormones after fear conditioning induces a generalized contextual fear response. This was accompanied by a selective and persistent increase in the excitability and number of activated DG granule cells. Selective chemogenetic suppression of these sparse cells in the DG prevented glucocorticoid-induced fear generalization and restored contextual memory specificity, while leaving expression of auditory fear memory unaffected., Conclusions: These results implicate the sparse ensemble of DG engram cells as a critical cellular substrate underlying fear generalization induced by glucocorticoid stress hormones., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Behçet's disease (BD) is a recurrent multisystemic disease responsible for occlusive vasculitis with arterial, venous and capillary involvement. The aim of this study was to determine the frequency and the features associated with the use of biotherapy in the management of patients followed in our department for BD., Methods: This is a retrospective study of patients medical records followed for BD in a department of internal medicine from January 2005 to August 2018., Results: A total of 41 patients were included with a mean age at diagnosis of 42.5±12.1 years (range 16 to 63) and a sex ratio men/women of 1.05. Oral and/or genital aphtosis was present in 70.7% of the patients. Other lesions were: ocular (78.0%), articular (46.3%), cutaneous (41.5%), central neurological (34.1%), vascular (26.8%), digestive (7.3%), pericardial (2.4%) and epididymal (2.4%). A biotherapy, interferon α and monoclonal antibodies, was used in 15 patients (36.6%), after failure of conventional treatments. The monoclonal antibodies were anti-TNFα (infliximab, adalimumab, certolizumab and golimumab) except in one patient for whom ustekinumab was used. Biotherapy was used in 46.9% of the patients with ocular involvement and never used in those patients without ocular involvement (P=0.01)., Conclusion: Biotherapy is effective and represents a solution to the failures of conventional treatments in severe forms of Behçet's disease with ocular involvement., (Copyright © 2019 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Inflammatory orbitopathies relate to an inflammatory state originating within the orbit and its adnexes, except the inner ocular globe. Orbital inflammation (OI) may be either localized manifestation of a proven or like autoimmune disease, or local response from immune system against infectious, structural or tumoral antigens. We review the clinical manifestations of OI, which provide helpful clues to the diagnosis and describe the inflammatory, infectious and neoplastic conditions classically associated with OI. Autoimmune diseases are probably the most common causes of OI associated with a bilateral dacryoadenitis (e.g., sarcoidosis, granulomatosis with polyangiitis, IgG4-related disease). We focused on a major part of the IgG4-RD spectrum, the IgG4-related orbital disease which has been recently described and the idiopathic orbital inflammation syndrome that one should consider in patients 40 years of age or older with non specific inflammation OI on biopsy but without underlying local or systemic disease. An algorithm for the diagnostic approach of OI was proposed. If systemic explorations fail to diagnose an underlying disease, histopathologic control is required for distinguishing non-specific OI from other differential diagnosis, especially lymphoma. In the cases of pure myositic locations and posteriorly located tumours where biopsy could damage to the optic nerve, analysis of orbital lesions in T2W IRM sequence may be helpful to distinguish idiopathic OI (IOI) from lymphoma. When the diagnostic work-up fails, a corticosteroid trial could be used, but its beneficial effect has to be cautiously interpretated before definitively diagnosing IOI. Finally, treatments used in main infllammatory orbitopathies were also reviewed., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Diagnostic work-up of uveitis involves many uncertainties. Search for an etiology should take into account the epidemiology of uveitis and focus on the most severe diseases or those, which can be treated. This work was undertaken to establish recommendations for the diagnosis work-up of uveitis., Methods: Recommendations were developed by a multidisciplinary panel of 15 experts, including internists, ophthalmologists and a rheumatologist and are based on a review of the literature with regard to effectiveness of investigations and the results of the ULISSE study, which is the first prospective study assessing the efficiency of a standardized strategy for the etiological diagnosis of uveitis. Children, immunocompromised patients, severe retinal vasculitis and specific ophthalmological entities are excluded from these recommendations., Results: Investigations should be first guided by the history and physical examination. Serological screening for syphilis is the only test appropriate in all forms of uveitis. If no diagnosis is made after this stage, we propose investigations guided by the anatomic characteristics of uveitis. It includes HLA B27 testing (in unilateral acute anterior non-granulomatous uveitis), serum angiotensin converting enzyme, interferon-gamma release assay and chest CT (chronic uveitis), cerebral MRI and anterior chamber tap with IL10 analysis (intermediate or posterior uveitis in patients over 40 years). Investigations ordered in the absence of orientation are almost always unhelpful., Conclusions: We propose a strategy for the etiologic diagnosis of uveitis. The recommendations should be updated regularly. The efficiency of more invasive investigations has yet to be evaluated., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Despite extensive investigations, including the use of Interferon-gamma release assays (IGRA), the diagnosis of intraocular tuberculosis (TB) remains challenging. Ocular evidence of Mycobacterium tuberculosis in low endemic countries for TB is extremely rare, leading mostly to a TB-related ocular inflammation presumptive diagnosis. This present work aims: to highlights the main clinical patterns suggestive of ocular TB; and the latest recommended guidelines for diagnosing ocular TB to clarify interferon-gamma release assay (IGRA) contribution and accuracy to the management of intraocular TB and its diagnosis, in addition to other available diagnostic tools, such as tuberculin skin test, bacteriologic and histologic analysis from intra/extra ocular sample and radiographic investigations; to define the accuracy of these diagnostic tools according to the endemic TB prevalence; and finally to identify therapeutic strategies adapted to the main clinical presentations of ocular TB. Our review of the literature shows that management of suspected ocular TB differs significantly based on whether patients are from high or low TB prevalence countries since accuracy of chest X-ray, tuberculin skin test and IGRA is significantly different. Taking into account these discrepancies, distinct guidelines should be determined for managing patients with suspected ocular TB, taking into consideration home prevalence of TB-patients., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Conventional immunosuppressive drugs, anti-TNF alpha and other biotherapies used in clinical practice are capable of controlling non-infectious anterior uveitis, posterior uveitis and panuveitis. The present work has been led by a multidisciplinary panel of experts, internists, rheumatologists and ophthalmologists and is based on a review of the literature. In case of corticodependency or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or anti-TNF alpha (adalimumab, infliximab) are used to achieve and maintain remission. Interferon is an efficient immunomodulatory treatment, as a second-line therapy, for some therapeutic indications (refractory macular edema, Behçet's vascularitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (corticosteroids, sirolimus etc.) are adjuvant therapies in case of unilateral inflammatory relapse. Therapeutic response must be evaluated precisely by clinical examination and repeated complementary investigations (laser flare photometry, multimodal imaging, perimetry, electroretinography measures)., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Scleritis is an inflammatory disease of the sclera; outer tunic of the eye on which the oculomotor muscles are inserted. It can be associated with a systemic disease up to one time out of 3. These associated diseases are mainly rheumatoid arthritis, vasculitis, including granulomatosis with polyangiitis in the first line and spondyloarthropathies. Before mentioning such an etiology, it is necessary to eliminate an infectious cause, mainly herpetic, which is regularly underestimated. The classification of scleritis is clinical. We distinguish between anterior scleritis and posterior scleritis. Anterior scleritis is diffuse or nodular, usually of good prognosis. Anterior necrotizing scleritis with inflammation is often associated with an autoimmune disease, necrotizing scleritis without inflammation usually reflects advanced rheumatoid arthritis. The treatment of these conditions requires close collaboration between internists and ophthalmologists to decide on the use of corticosteroid therapy with or without immunosuppressors or biotherapies., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Hyper-IgE may be found under many pathological conditions. The role of IgE is essentially associated with the occurrence of allergic manifestations, which may be accompanied by an increase of their serum levels. Elevation of total IgE has also been reported in association with certain rare genetic immune deficiencies called hyper-IgE syndromes. Other circumstances such as infectious diseases, tumors or autoimmune diseases may also be accompanied by an excessive synthesis of IgE. Considering the diversity of these situations, discussion of the prognostic value of total IgE is useful to the internist., (Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Purpose: ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance., Methods: ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not., Results: Among the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first step's systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second step's most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon® (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed., Conclusion: Only a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Systemic lupus erythematosus (SLE) is a chronic disease that considerably hampers patient's daily living. Qualitative studies with patients' interviews have been conducted to describe the experiences and perspectives of adults living with SLE. Among existing generic and disease-specific quality of life (QOL) questionnaires, none succeeded to exhaustively measure patient's preoccupations. However, these tools are useful to quantify the burden of the disease. Social precariousness, socioeconomic status and education level are intimately correlated to QOL measures, either generic or disease-specific. Musculoskeletal disease activity is also associated with a lower QOL. Using disease-specific tools may be useful because of a better aptitude to record an improvement in health status. Moreover, using generic and disease-specific questionnaires together may help to identify factors associated with a lower quality of life but not related to SLE from the patient's perspective (such as smoking or obesity). Developing new ways of recording QOL data in the future may help to evaluate the real benefit of using QOL scales in daily practice., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Purpose: Diagnosis of uveitis is difficult. Etiologic investigations should take into account the epidemiology of uveitis and should focus on the most severe forms of the disease and those which can be treated. This study was undertaken to establish recommendations for the diagnosis of uveitis., Methods: Recommendations were developed by a multidisciplinary panel of 14 experts, including internists, ophthalmologists, and rheumatologists, and are based on a review of the literature and the results of the ULISSE study, which was the first prospective study to assess the efficacy of a standardized strategy for the etiologic diagnosis of uveitis. The following groups of patients are not included in these recommendations: children, immunocompromised patients, patients with severe retinal vasculitis, and those with specific eye diseases diagnosed by ophthalmologic examination only., Results: Diagnosis should be guided by the medical history of the patient and physical examination. Serologic screening for syphilis is appropriate in all forms of uveitis. If uveitis is not diagnosed at this stage, investigations oriented by the anatomic characteristics of uveitis are proposed. These consist of assays for HLA-B27 (in unilateral acute anterior non-granulomatous uveitis), serum angiotensin-converting enzyme, interferon-gamma release, chest computed tomography (chronic uveitis), cerebral magnetic resonance imaging and anterior chamber tap with interleukin-10 analysis (intermediate or posterior uveitis in patients >40years-old). Other investigations prescribed in the absence of orientation are usually unhelpful., Conclusions: A strategy is proposed for the etiologic diagnosis of uveitis. The benefit of more invasive investigations remains to be determined., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Uveomeningitis relates to an inflammatory state extending from iris and ciliary bodies to the choroid behind the eye. Because of a close contact between eye and brain, and barrier disruption, the inflammation can spread into the central nervous system (CNS). We review the clinical manifestations of uveitis, which are known to provide helpful clues to the diagnosis and describe the infectious, inflammatory, and neoplastic conditions classically associated with the uveomeningitis. Inflammatory or auto-immune diseases are probably the most common clinically recognized causes of uveomeningitis associated with a significant pleiocytosis. These entities often cause inflammation of various tissues in the body, including ocular structures and the meninges (i.e., sarcoidosis, Behçet's disease, and Vogt-Koyanagi-Harada syndrome). The association of an infectious uveitis with an acute or a chronic meningo-encephalitis is unusual but occasionally the eye examination may suggest an infectious etiology or even a specific organism responsible for an uveomeningitis. One should consider the diagnosis of primary ocular-CNS lymphoma in patients of 40 years of age or older with bilateral uveitis, especially with prominent vitritis, showing poor response to corticosteroid therapy. Finally, an algorithm for the diagnostic approach of uveomeningitis is proposed., (Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Biotherapies used in clinical practice for the treatment of uveitis include monoclonal antibodies and fusion proteins (anti-TNFα, anakinra, tocilizumab and rituximab), interferons (IFN) and intravenous immunoglobulins (IVIg). IFN is capable of inducing prolonged remission and continued after his discontinuation, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behçet's disease. They are generally (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIg are used for the treatment of Birdshot's disease. Tolerance of IVIg is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1r) showed interesting results in terms of efficiency in one small open study in Behçet's disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis., (Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Birt-Hogg-Dubé (SBHD) syndrome is a rare autosomal dominant genodermatosis, predisposing to the occurrence of tumors associated with skin manifestations. We report a male patient who presented with a history of recurrent pneumothorax and was treated by nephrectomy for a left kidney carcinoma at 20 years old. Skin examination disclosed numerous fibrofolliculomas of the scalp. During follow-up, surgical resection of parotid oncocytomas and of a parathyroid adenoma were performed. SBHD was confirmed by molecular biology. In the presence of fibrofolliculomas and kidney tumors and recurrent spontaneous pneumothorax, a diagnosis of SHBD syndrome should be discussed, and tests need to be performed on the whole family., (Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Interferon-beta (IFN-beta) therapy can trigger immune adverse effects. We report a patient, who was treated for multiple sclerosis (MS) by IFN-beta during 3 years before developing a severe colitis due to Crohn's disease (CD). Neurological manifestations may occur in CD but rarely mimic MS. This report's points highlight the possible association of MS and CD, where IFN-beta therapy probably unmasked CD. Indeed, similar cases of CD flares have been reported after IFN-alpha therapy for chronic C hepatitis.

Introduction: Celiac disease is a common condition with a prevalence of about 1%. Clinical extradigestive presentations are various and stroke can be one of the neurological manifestations., Exegesis: Two cases of stroke occurring in young adults are described, leading to the diagnosis of celiac disease. Hyperhomocysteinemia or cerebral arterial vasculopathy in one case and antiphospholipid syndrome in the other case are thought to be involved in the pathogenesis of stroke during celiac disease., Conclusion: The possible presence of celiac disease should be discussed in unexplained young adult stroke.

Introduction: Anterior scleritis is defined as an inflammation of the sclera, located anteriorly to the equator of the eye. Cotrimoxazole is an antibiotic with an immunomodulatory action., Exegesis: In case of idiopathic anterior scleritis or scleritis associated with autoimmune diseases, immunosuppressive treatment is often required. We report on six patients with anterior idiopathic scleritis non sensitive to local treatment where cotrimoxazole improved or cured the symptoms., Conclusion: Cotrimoxazole seems to be an interesting therapeutic treatment in non threatening anterior scleritis.

The electroporative transfer of gene DNA and other bioactive substances into tissue cells by electric pulses gains increasing importance in the new disciplines of electrochemotherapy and electrogenetherapy. The efficiency of the electrotransfer depends crucially on the adsorption of the gene DNA and oligonucleotides to the plasma cell membranes. Here it is shown that the adsorption of larger oligonucleotides such as fragments (ca. 300 bp) of sonicated calf-thymus DNA, to anionic lipids of unilamellar vesicles (diameter Phi=300+/-90 nm) is greatly enhanced by divalent cations such as Ca(2+)-ions. Applying centrifugation, bound and free DNA are monitored optically at the wavelength lambda=260 nm. Using arsenazo III as a Ca(2+)-indicator and atomic absorption spectroscopy (AAS), Ca(2+)-titrations of DNA and vesicles yield the individual equilibrium constants of Ca(2+)- and DNA-binding not only for the binary complexes: Ca/lipids, Ca/DNA and DNA/lipids, respectively, but also for the various processes to form the ternary complex DNA/Ca/lipids. The data provide the basis for goal-directed optimization protocols for the adsorption and thus efficient electrotransfer of oligonucleotides and polynucleotides into cells.

Purpose: McArdle's disease (MAD) or glycogen storage disease type V, usually starts in childhood or adolescence. Generally diagnosis is made before the early adulthood because patients present well defined syndrome and are constrained., Method: We retrospectively investigated all MAD cases diagnosed in the biochemical laboratory from Debrousse Hospital in Lyon, during 40 years (1962-2002). We then selected patients whose diagnosis had been made after 30 years., Results: Fifteen patients answered our criteria but only 11 files could be analysed. A twelfth patient (service of internal medicine--Royan) supplemented the series. We sought the reasons of a late diagnosis: early age of beginning but few symptoms (7 cases), age of beginning higher than 20 years (5 cases including 3 after 45 years). The principal symptoms were muscular deficit and muscular pains (8 cases) and second wind phenomenon (7 cases). Creatinine phosphokinase level was constantly high. Ischemic effort test when it was carried out was constantly abnormal. Conversely electromyogram was often normal (5 cases). Several biopsies were necessary in a third of the cases to evoke the diagnosis, particularly among the patients with late onset symptoms., Conclusion: Diagnosis of metabolic MAD is generally easy if the interrogation finds inaugural symptoms in childhood or adolescence even if the patient consults very late in the life. The diagnosis can become much more difficult if it begins late in life (atypical symptoms, need for several muscular biopsy).

To enable high-throughput screening of molecular phenotypes, multi-parameter fluorescence microscopy is applied. Object of our study is lymphocytes which invade human tissue. One important basis for our collaborative project is the development of methods for automatic and accurate evaluation of fluorescence micrographs. As a part of this, we focus on the question of how to measure the accuracy of microscope image interpretation, by human experts or a computer system. Following standard practice we use methods motivated by receiver operator characteristics to discuss the accuracies of human experts and of neural network-based algorithms. For images of good quality the algorithms achieve the accuracy of the medium-skilled experts. In images with increased noise, the classifiers are outperformed by some of the experts. Furthermore, the neural network-based cell detection is much faster than the human experts.

Introduction: Interferon-alpha (IFN alpha) used to treat chronic hepatitis C can be responsible for some side effects. We report two cases of sarcoidosis which appeared in patients treated with IFN alpha and ribavirin for chronic hepatitis C., Exegesis: A first patient, treated for 5 months with IFN alpha and ribavirin because of chronic hepatitis C, after the failure of a first treatment with IFN alpha alone, was hospitalized for dyspnea. The chest X-ray and scanner revealed an interstitial syndrome and mediastinal adenopathies. Biopsies of bronchial spurs revealed epithelioid and giganto-cellular granuloma. After discontinuation of antiviral treatment and starting corticosteroid therapy, the evolution was favourable but viremia reappeared. A second patient with IFN alpha and ribavirin for 4 months because of chronic hepatitis C (after the failure of a first treatment with IFN alpha alone) was hospitalized for fever, arthralgias, erythema nodosa and modification of previous skin scars. The biopsy of a scar showed an epithelioid and giganto-cellular granuloma. After discontinuation of antiviral therapy and starting corticosteroid treatment, the evolution was favourable., Conclusion: Some publications mention occurrence of sarcoidosis during IFN alpha therapy, occasionally associated with ribavirin, disappearing after discontinuation of the treatment, though sometimes corticotherapy is necessary. The roles of IFN alpha and ribavirin are discussed.

Introduction: Periarteritis nodosa can be associated with streptococcal infections in children. We report two cases of adult cutaneous periarteritis nodosa that disappeared after the treatment of dental infection., Exegesis: A 23-year-old woman presented with necrotic ulceration on the legs for 6 months, with a histology of necrotizing vasculitis. Many sites of dental infections could be noted. Immunological data were negative and so were serologies of hepatitis. Corticosteroid therapy failed. The teeth removal with antibiotic therapy allowed the disappearance of cutaneous lesions in a month. A 26-year-old woman was hospitalized for growing thin, fever, diffuse arthralgia and myalgia and cutaneous nodules on the legs with necrotizing vasculitis on dermal vessels at histological analysis. The biology showed no pecularity. Radiography of the teeth showed many dental infection sites. The removal of six teeth with antibiotic therapy led to the disappearance of vasculitis in 6 weeks., Conclusion: The search for an infectious problem is important when vasculitis is diagnosed, in particular periarteritis nodosa. The treatment of dental infection could occasionally mean avoiding immunosuppressive therapy in certain cases.

A retrospective multicentric study was conducted to determine the real prevalence of underlying iron overloads during Yersinia bacteremias. Ninety-seven cases of bacteremias (84 Yersinia enterocolitica, 13 Yersinia pseudotuberculosis) were registered between 1990 and 1996 in eastern France. Available data were collected in 70 cases (72.2%). Laboratory investigations of iron status were done in 53% (37/70). Three patients had a past record of known hemochromatosis, meanwhile in nine other cases an iron overload was discovered during the Yersinia bacteremia. Two cases of hemochromatosis were confirmed by liver histology. In all of these 12 cases, Yersinia enterocolitica was the causal agent. The effective prevalence of underlying iron overload in Yersinia bacteremias is 40% when researched, greater than data commonly published (1.8-14%), showing both epidemiological and clinical under estimation of iron's importance in Yersinia infection pathogenesis. A Yersinia bacteremia must be considered as an indicator of possible iron overload. Yersinia infection must be suspected in febrile hemochromatosic patients. A multicentric study must be conducted to evaluate incidence and characteristics of bacteremias in hemochromatosic patients.

Twenty one cases of the association systemic scleroderma and cancer are reported. Neoplasic localisations were the following: pulmonary five cases; breast two cases; esophageal cancer one case; stomach one case; colon one case; uterus four cases; ovarian cancer one case; prostatic cancer one case; renal cancer one case; malignant hemopathies six cases. In the literature, more than three hundred cases of such an association have been reported since 1886, essentially lung cancers (more than 100). Recent epidemiological studies allow to conclude to a higher frequency of lung and breast cancers. We suggest that systemic scleroderma patients should be examined attentively and carefully for these risks.

Steroid myopathy is one of the various side effects of prolonged treatments, particularly with the 9 alpha fluorinated steroids. The receptor protein probably plays a major role with a decrease in protein synthesis. There is no mean to detect this myopathy before clinical signs appear. Neither muscular testing nor enzymes nor electromyography give arguments and muscular biopsy is aggressive. Low density scanner and MNR could help diagnosis. Frequency of disease is not known. A total cumulative maintenance steroid dosage of 400 mg can be sufficient. Proximal muscles are usually involved, quadriceps and other pelvic girdle muscles being more severely affected. Fast twitch glycolytic type IIB fibers are particularly susceptible. Physical exercise is effective in preventing myopathy. Nevertheless, no special rehabilitation program has been tested for the moment in human beings.

The authors report the case of a 54-year old woman presenting with right cardiac failure in whom the diagnosis of contemporaneous cutaneous-systemic mast cell disease was made. The cardiac symptoms regressed concomitantly with the vasomotor manifestations of the mast cell disease. Following a review of the principal mast cell mediators, the cardiovascular manifestations of the disease are studied and pathogenetic hypotheses are being put forward.

Paraneoplastic acute polyarthritis (PAP) is a recognized rheumatological entity with semeiological features that are based only on a few published cases. We thought that it would be of interest to review the literature and present the current characteristics of PAP, taking into account only those cases where the acute polyarthritis and a neoplastic disease followed parallel courses. The clinical manifestations of PAP are extremely varied, making it difficult to distinguish this disease from some forms of rheumatoid arthritis, the RS3 PE syndrome or polymyalgia rheumatica. Clinicians must be vigilant when they are faced with a particularly progressive acute polyarthritis in a patient aged over 60, and particularly when this patient's general condition is altered and when fever and a clear-cut inflammatory syndrome are present. In such circumstances, it is mandatory to investigate for an underlying neoplasia.

Whether or not the association of systemic scleroderma and carcinoma is fortuitous is a much debated subject. Since 1886, approximately 320 cases of this association have been published. The most frequent malignancy involved is lung cancer (102 cases), followed by breast cancer (52 cases), malignant blood diseases (46 cases), cancer of the oesophagus (20 cases) and other gynaecological or gastrointestinal malignant tumours. A recent epidemiological study has shown that lung cancer is significantly more frequent than other malignancies, but statistical data on the latter are lacking. However, it would be wise to recommend that patients with systemic scleroderma should be regularly examined for gynaecological, haematological and gastrointestinal malignant diseases.

The protein C system--a complex physiological coagulation inhibition system--is a major regulator which controls thrombin production. Nowadays, its exploration is indispensable for the detection of constitutional or acquired protein C deficiency, side by side with a search for antithrombin III deficiency. This approach, based on the frequent association of recurrent thrombosis, mainly venous, in young subjects with congenital deficiencies, makes it possible to initiate, beside a family survey, an individual and efficient prophylaxis of recurrent thrombosis.

Herpesvirus infections are thought to be cofactors of the human immunodeficiency virus (HIV) disease, and high concentrations of acyclovir (ACV) are active on all herpesviruses. Because ACV was shown to delay the cytopathic effect of HIV in vitro, we evaluated the effect of intermittent high doses of ACV in mildly symptomatic HIV-patients in a randomized double-blind placebo-controlled trial with a 4-month treatment period. A total of 30 CDC II and III patients were enrolled; 24 (80%) completed the study. Placebo and ACV were given once a week in a 3-h infusion with 1 g oral probenecid. Each dose of ACV was 50 mg/kg. Pharmacokinetic data were obtained from patients of the preliminary open study. The obtained concentrations were effective against both herpesviruses and HIV: peak concentrations were 197 and 11 mumol/l in serum and CSF, respectively; the CSF:serum ratio of the areas under the curve was 82%. Two patients with placebo acquired hairy leukoplakia and detectable antigenemia vs. none in the ACV group (p = 0.23). T-helper cell count over the 4-month period decreased in the placebo group while it increased in the ACV-treated group (mean of change = -105 c/microliters vs. +68 c/microliters; p = 0.06). beta 2-microglobulin increased with placebo and did not with ACV (mean of change = +0.63 mg/l vs. -0.27 mg/l, p less than 0.025). Only one patient had, at one time, transient elevation of creatinemia related to ACV. We concluded that weekly high doses of ACV were able to delay the progression of some significant markers of HIV disease. Thus, preventive/prophylactic treatment of herpesvirus infections could be useful in mildly symptomatic HIV patients. Further larger trials using a more feasible treatment are warranted.