Idiopathic inflammatory myopathies can be classified as polymyositis, dermatomyositis, immune-med... more Idiopathic inflammatory myopathies can be classified as polymyositis, dermatomyositis, immune-mediated necrotizing myopathy, sporadic inclusion body myositis or non-specific myositis. Anti-Jo-1 antibody-positive patients are assigned to either polymyositis or dermatomyositis suggesting overlapping pathological features. We aimed to determine if anti-Jo-1 antibody-positive myopathy has a specific morphological phenotype. In a series of 53 muscle biopsies of anti-Jo-1 antibody-positive patients, relevant descriptive criteria defining a characteristic morphological pattern were identified. They were tested in a second series of anti-Jo-1 antibody-positive patients and compared to 63 biopsies from patients suffering from other idiopathic inflammatory myopathies. In anti-Jo-1 antibody-positive patients, necrotic fibres, which strongly clustered in perifascicular regions, were frequently observed. Sarcolemmal complement deposition was detected specifically in perifascicular areas. Inflamm...
To evaluate a possible implication of cytokines in the patho- genesis of polyneuropathy, organome... more To evaluate a possible implication of cytokines in the patho- genesis of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, we studied five consecutive patients with this condition, of which four had sclerotic bone lesions and four had multicentric Cas- tleman's disease. Interleukin-18 (IL-lp) and IL-6 serum levels were determined in these patients (13 serum samples) and in
Patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis (MMF) complain of arth... more Patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis (MMF) complain of arthromyalgias, chronic fatigue and cognitive deficits. This study aimed to characterize brain perfusion in these patients. Brain perfusion SPECT was performed in 76 consecutive patients (aged 49±10 y) followed in the Garches-Necker-Mondor-Hendaye reference center for rare neuromuscular diseases. Images were acquired 30 min after intravenous injection of 925 MBq 99mTc-ethylcysteinate dimer (ECD) at rest. All patients also underwent a comprehensive battery of neuropsychological tests, within 1.3±5.5 mo from SPECT. Statistical parametric maps (SPM12) were obtained for each test using linear regressions between each performance score and brain perfusion, with adjustment for age, sex, socio-cultural level and time delay between brain SPECT and neuropsychological testing. SPM analysis revealed positive correlation between neuropsychological scores (mostly exploring executive functions) and brain ...
Transactions of the Royal Society of Tropical Medicine and Hygiene
Ten unselected African patients infected with human immunodeficiency virus (HIV) and with slim di... more Ten unselected African patients infected with human immunodeficiency virus (HIV) and with slim disease were evaluated using physical examination, anthropometric measurements, Karnovsky performance score, and muscle biopsy. All had marked weight loss (36.8 +/- 10.8%) with extreme fatigue, marked diffuse wasting with significantly decreased circumferences of arms, thighs and calves (P < or = 0.002), and a low Karnovsky performance score (range 30-70). Mild to moderate motor deficit (in 9/10 patients) contrasted with the major amyotrophy. Chronic diarrhoea (in 7/10) and/or prolonged fever (in 7/10) were always associated with the amyotrophy. Atrophy of muscle fibers was the main finding of muscle biopsy. Only 5 patients met the CDC criteria for the 'HIV wasting syndrome'. We conclude that slim disease, which is highly suggestive of the acquired immune deficiency syndrome (AIDS) in Africa, is a condition associated with chronic diarrhoea and/or prolonged fever, that encompass...
Neuropathology and applied neurobiology, Jan 25, 2015
To analyse the paradox of a lack of giant cell formation and fibrosis in chronic lesions of macro... more To analyse the paradox of a lack of giant cell formation and fibrosis in chronic lesions of macrophagic myofasciitis (MMF) in comparison to muscular sarcoidosis (MuS). Inflammatory lesions and contiguous muscle regions from biopsy samples of ten patients with MuS and ten patients with MMF were cut out by laser microdissection. Mediators of the T helper cell (Th)1 inducing classical macrophage activation (e.g. STAT1, IFNγ and CXCR3), and Th2 inducing alternative activation of macrophages (e.g. CD206/MRC1, STAT6, SOCS1), molecules involved in development of fibrosis (e.g. TGFβ) and giant cells (e.g. TYROBP) were assessed by immunohistochemistry and real-time PCR. STAT6-induced Th2 immunity was associated with up-regulated gene expression of MRC1, SOCS1 and TGFB in inflammatory foci, in comparison to adjacent tissue. TYROBP and TREM2, genes regulating giant cell formation, were more strongly expressed in lesions of MuS patients than in those of MMF. TGFβ co-localized with CD206(+) macr...
Journal of muscle research and cell motility, 1998
We developed a short-time assay to evaluate muscle satellite cell migration, based on the fact th... more We developed a short-time assay to evaluate muscle satellite cell migration, based on the fact that during myogenic differentiation, myoblasts migrate preferentially towards high cellular density areas where myotubes would form. This assay consists of a computer-assisted count of cells within a randomly chosen field, performed every hour for eight hours, and compared with the cell number at the start time of the experiment. Nine primary myoblast cultures were tested in triplicate. The method relies on several requisites. (1) Negligible cell proliferation: cell division was nearly absent in 8 h experiments. (2) Directional cell movement: a major flow of cells, either entering or exiting the fields, was constantly observed. 'Counter-flows', detected by visual counting, involved minor percentages of cells. (3) Constant migration rate: a linear increase in cell count variations over 8 h and a very high degree of intra-assay homogeneity were observed. Individual primary cell cult...
a d ˆ´ e ´´ ˆ ´ Abstract Objective: Transplantation of skeletal myogenic precursor cells (mpc) in... more a d ˆ´ e ´´ ˆ ´ Abstract Objective: Transplantation of skeletal myogenic precursor cells (mpc) into the myocardium using a non-surgical procedure. Methods: Closed-chest mpc transplantation was assessed in pigs using the NOGA-Biosense device allowing both electromechanical mapping of the left ventricle (LV), and guided mpc injections through endocardium. Results: We successively established that: (1) adequate preimplantation handling
Little is known about systemic sclerosis (SSc)-related myopathy. We aimed to compare the clinical... more Little is known about systemic sclerosis (SSc)-related myopathy. We aimed to compare the clinical and immunological features of SSc patients with or without associated myopathy. Forty SSc patients with myopathy, defined by myalgia or muscle weakness associated with creatine kinase (CK) more than five times the upper limit range or myopathic electromyography (EMG) or abnormal myopathology, were identified from the records of four French hospital centres. For each patient, we selected two SSc controls matched for cutaneous SSc form, sex, age at SSc onset, and disease duration. We performed a case-control study testing clinical and immunological SSc-related features for association with myopathy by conditional logistic regression. Muscle and SSc features of patients with myopathy did not differ significantly among the four centres of origin. Only four (10%) patients with SSc-associated myopathy had anti-polymyositis-scleroderma (PM-Scl) antibodies. Case-control univariate analysis revealed that reduced forced vital capacity (FVC) [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.3-34.9], heart involvement, defined as clinical congestive heart failure, left ventricular ejection fraction (LVEF) &lt; 60%, arrhythmia or conductive abnormalities (OR 2.9, 95% CI 1.3-6.5), and scleroderma renal crisis (OR 3.0, 95% CI 1.3-34.9) were significantly more frequent in patients with myopathy than in controls. Two autoantibodies were more frequent in patients with myopathy: anti-PM-Scl (OR 5.0, 95% CI 1.1-23.9) and anti-RNP (OR 6.9, 95% CI 1.1-64.4). Multivariate analysis retained two variables associated positively with myopathy [reduced FVC (OR 3.1, 95% CI 1.3-9.8) and heart involvement (OR 2.5, 95% CI 1.1-7.1)], while anti-centromere antibodies were associated negatively (OR 0.11, 95% CI 0.03-0.53). Heart monitoring of SSc patients with myopathy should be undertaken regularly because of the association of myocardial and skeletal myopathies in such patients.
Idiopathic inflammatory myopathies can be classified as polymyositis, dermatomyositis, immune-med... more Idiopathic inflammatory myopathies can be classified as polymyositis, dermatomyositis, immune-mediated necrotizing myopathy, sporadic inclusion body myositis or non-specific myositis. Anti-Jo-1 antibody-positive patients are assigned to either polymyositis or dermatomyositis suggesting overlapping pathological features. We aimed to determine if anti-Jo-1 antibody-positive myopathy has a specific morphological phenotype. In a series of 53 muscle biopsies of anti-Jo-1 antibody-positive patients, relevant descriptive criteria defining a characteristic morphological pattern were identified. They were tested in a second series of anti-Jo-1 antibody-positive patients and compared to 63 biopsies from patients suffering from other idiopathic inflammatory myopathies. In anti-Jo-1 antibody-positive patients, necrotic fibres, which strongly clustered in perifascicular regions, were frequently observed. Sarcolemmal complement deposition was detected specifically in perifascicular areas. Inflamm...
To evaluate a possible implication of cytokines in the patho- genesis of polyneuropathy, organome... more To evaluate a possible implication of cytokines in the patho- genesis of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, we studied five consecutive patients with this condition, of which four had sclerotic bone lesions and four had multicentric Cas- tleman's disease. Interleukin-18 (IL-lp) and IL-6 serum levels were determined in these patients (13 serum samples) and in
Patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis (MMF) complain of arth... more Patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis (MMF) complain of arthromyalgias, chronic fatigue and cognitive deficits. This study aimed to characterize brain perfusion in these patients. Brain perfusion SPECT was performed in 76 consecutive patients (aged 49±10 y) followed in the Garches-Necker-Mondor-Hendaye reference center for rare neuromuscular diseases. Images were acquired 30 min after intravenous injection of 925 MBq 99mTc-ethylcysteinate dimer (ECD) at rest. All patients also underwent a comprehensive battery of neuropsychological tests, within 1.3±5.5 mo from SPECT. Statistical parametric maps (SPM12) were obtained for each test using linear regressions between each performance score and brain perfusion, with adjustment for age, sex, socio-cultural level and time delay between brain SPECT and neuropsychological testing. SPM analysis revealed positive correlation between neuropsychological scores (mostly exploring executive functions) and brain ...
Transactions of the Royal Society of Tropical Medicine and Hygiene
Ten unselected African patients infected with human immunodeficiency virus (HIV) and with slim di... more Ten unselected African patients infected with human immunodeficiency virus (HIV) and with slim disease were evaluated using physical examination, anthropometric measurements, Karnovsky performance score, and muscle biopsy. All had marked weight loss (36.8 +/- 10.8%) with extreme fatigue, marked diffuse wasting with significantly decreased circumferences of arms, thighs and calves (P < or = 0.002), and a low Karnovsky performance score (range 30-70). Mild to moderate motor deficit (in 9/10 patients) contrasted with the major amyotrophy. Chronic diarrhoea (in 7/10) and/or prolonged fever (in 7/10) were always associated with the amyotrophy. Atrophy of muscle fibers was the main finding of muscle biopsy. Only 5 patients met the CDC criteria for the 'HIV wasting syndrome'. We conclude that slim disease, which is highly suggestive of the acquired immune deficiency syndrome (AIDS) in Africa, is a condition associated with chronic diarrhoea and/or prolonged fever, that encompass...
Neuropathology and applied neurobiology, Jan 25, 2015
To analyse the paradox of a lack of giant cell formation and fibrosis in chronic lesions of macro... more To analyse the paradox of a lack of giant cell formation and fibrosis in chronic lesions of macrophagic myofasciitis (MMF) in comparison to muscular sarcoidosis (MuS). Inflammatory lesions and contiguous muscle regions from biopsy samples of ten patients with MuS and ten patients with MMF were cut out by laser microdissection. Mediators of the T helper cell (Th)1 inducing classical macrophage activation (e.g. STAT1, IFNγ and CXCR3), and Th2 inducing alternative activation of macrophages (e.g. CD206/MRC1, STAT6, SOCS1), molecules involved in development of fibrosis (e.g. TGFβ) and giant cells (e.g. TYROBP) were assessed by immunohistochemistry and real-time PCR. STAT6-induced Th2 immunity was associated with up-regulated gene expression of MRC1, SOCS1 and TGFB in inflammatory foci, in comparison to adjacent tissue. TYROBP and TREM2, genes regulating giant cell formation, were more strongly expressed in lesions of MuS patients than in those of MMF. TGFβ co-localized with CD206(+) macr...
Journal of muscle research and cell motility, 1998
We developed a short-time assay to evaluate muscle satellite cell migration, based on the fact th... more We developed a short-time assay to evaluate muscle satellite cell migration, based on the fact that during myogenic differentiation, myoblasts migrate preferentially towards high cellular density areas where myotubes would form. This assay consists of a computer-assisted count of cells within a randomly chosen field, performed every hour for eight hours, and compared with the cell number at the start time of the experiment. Nine primary myoblast cultures were tested in triplicate. The method relies on several requisites. (1) Negligible cell proliferation: cell division was nearly absent in 8 h experiments. (2) Directional cell movement: a major flow of cells, either entering or exiting the fields, was constantly observed. 'Counter-flows', detected by visual counting, involved minor percentages of cells. (3) Constant migration rate: a linear increase in cell count variations over 8 h and a very high degree of intra-assay homogeneity were observed. Individual primary cell cult...
a d ˆ´ e ´´ ˆ ´ Abstract Objective: Transplantation of skeletal myogenic precursor cells (mpc) in... more a d ˆ´ e ´´ ˆ ´ Abstract Objective: Transplantation of skeletal myogenic precursor cells (mpc) into the myocardium using a non-surgical procedure. Methods: Closed-chest mpc transplantation was assessed in pigs using the NOGA-Biosense device allowing both electromechanical mapping of the left ventricle (LV), and guided mpc injections through endocardium. Results: We successively established that: (1) adequate preimplantation handling
Little is known about systemic sclerosis (SSc)-related myopathy. We aimed to compare the clinical... more Little is known about systemic sclerosis (SSc)-related myopathy. We aimed to compare the clinical and immunological features of SSc patients with or without associated myopathy. Forty SSc patients with myopathy, defined by myalgia or muscle weakness associated with creatine kinase (CK) more than five times the upper limit range or myopathic electromyography (EMG) or abnormal myopathology, were identified from the records of four French hospital centres. For each patient, we selected two SSc controls matched for cutaneous SSc form, sex, age at SSc onset, and disease duration. We performed a case-control study testing clinical and immunological SSc-related features for association with myopathy by conditional logistic regression. Muscle and SSc features of patients with myopathy did not differ significantly among the four centres of origin. Only four (10%) patients with SSc-associated myopathy had anti-polymyositis-scleroderma (PM-Scl) antibodies. Case-control univariate analysis revealed that reduced forced vital capacity (FVC) [odds ratio (OR) 3.0, 95% confidence interval (CI) 1.3-34.9], heart involvement, defined as clinical congestive heart failure, left ventricular ejection fraction (LVEF) &lt; 60%, arrhythmia or conductive abnormalities (OR 2.9, 95% CI 1.3-6.5), and scleroderma renal crisis (OR 3.0, 95% CI 1.3-34.9) were significantly more frequent in patients with myopathy than in controls. Two autoantibodies were more frequent in patients with myopathy: anti-PM-Scl (OR 5.0, 95% CI 1.1-23.9) and anti-RNP (OR 6.9, 95% CI 1.1-64.4). Multivariate analysis retained two variables associated positively with myopathy [reduced FVC (OR 3.1, 95% CI 1.3-9.8) and heart involvement (OR 2.5, 95% CI 1.1-7.1)], while anti-centromere antibodies were associated negatively (OR 0.11, 95% CI 0.03-0.53). Heart monitoring of SSc patients with myopathy should be undertaken regularly because of the association of myocardial and skeletal myopathies in such patients.
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Papers by Romain Gherardi