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We propose the angular distribution of lepton pairs produced in ultrarelativistic heavy-ion collisions as a probe of thermalization of the quark-gluon plasma. We focus on dileptons with invariant masses large enough that they are produced through quark-antiquark annihilation in the early stages of the collision. The angular distribution of the lepton in the rest frame of the pair then reflects the angular distribution of quark momenta. At early times, the transverse pressure of the quark-gluon plasma is larger than its longitudinal pressure as a result of the fast longitudinal expansion, which results in an oblate lepton distribution. By contrast, direct (Drell-Yan) production by quarks and antiquarks from incoming nuclei, whose momenta are essentially longitudinal, results in a prolate distribution. As the invariant mass increases, Drell-Yan gradually becomes the dominant source of dilepton production, and the lepton distribution evolves from oblate to prolate. The invariant mass at which the transition occurs is highly sensitive to the equilibration time of the quark-gluon plasma or, equivalently, the shear viscosity over entropy ratio η/s in the early stages of the collision.

Introduction: X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive myopathy due to recently reported mutations in the VMA21 gene., Methods: Four men from 2 separate families were studied. The clinical presentation, genetic data, muscle biopsy, and muscle MRI were analyzed., Results: A known VMA21 mutation, c.163+4A>G, and a new mutation, c.163+3A>G, respectively, were found in the 2 families. The clinical course was characterized by onset in childhood and progressive muscle weakness with a limb-girdle pattern. Muscle biopsy revealed a mild myopathy with an increased number of giant autophagic vacuoles. Whole-body muscle MRI showed that pelvic girdle and proximal thighs were the most and earliest affected territories, with sparing of rectus femoris muscles. Muscle changes essentially consisted of degenerative fatty replacement., Conclusions: This study highlights a distinctive MRI pattern of muscle involvement, which can be helpful for diagnosis of XMEA, even before muscle biopsy or genetic analysis., (© 2015 Wiley Periodicals, Inc.)

We report on 31 patients and 3 affected siblings (17 males and 17 females) from Southern France with McArdle disease (two from Spanish and three from Portuguese background). Molecular analysis revealed the presence of five previously described mutations: the common p.R50X nonsense mutation, the p.R94W and p.V456M missense mutations, the p.K609K conservative mutation which generates an aberrant splicing, and the p.K754fs frameshift mutation; and 10 new molecular defects: eight missense mutations at homozygous (p.G136D) or heterozygous state (p.T379M, p.G449R, p.T488I, p.R490Q, p.R570Q, p.R590H, and p.R715W), one nonsense mutation p.R650X and one deletion (p.delK170). Our results confirm that the p.R50X nonsense mutation is also the most common associated with myophosphorylase deficiency in the Southern French population: 21 of 25 French unrelated patients (15 homozygous and six heterozygous, i.e., 72% of the mutated alleles). Two patients, one from Algeria and one from Tunisia, were homozygous for a previously identified missense mutation p.V456M in a Moroccan subject. Our findings further demonstrate molecular heterogeneity of myophosphorylase deficiency, absence of genotype-phenotype correlation and expand the already crowded map of mutations within the myophosphorylase gene. Our study also provides evidence for increased medical interest of malignant hyperthermia susceptibility (MHS) because of 34 McArdle disease patients, three and two affected siblings were contracture-tested and found to be positive.

Introduction: An inflammatory myopathy, characterised by joint and muscle pain, chronic asthenia, with infiltration of peri-fascicular epimysium, perimysium and endomysium by cells of the macrophagic line, macrophagic myofasciitis is often associated with other, generally auto-immune, affections. However, the coexistence with another inflammatory myopathy is relatively rare., Observation: A 29 year-old woman presented with 2 distinct inflammatory myopathies, a macrophagic myofasciitis and a dermatomyositis, which had appeared a few years after., Discussion: In the rare cases in which 2 inflammatory myopathies are combined, the precise relationship between them is unknown, an individual susceptibility to developing muscle diseases is suggested.

Objectives: To document 2 apparently incongruous clinical disorders occurring in the same infant: congenital myopathy with myophosphorylase deficiency (McArdle disease) and mitochondrial hepatopathy with liver failure and mitochondrial DNA depletion., Methods: An infant girl born to consanguineous Moroccan parents had severe congenital hypotonia and hepatomegaly, developed liver failure, and died at 5 months of age. We studied muscle and liver biopsy specimens histochemically and biochemically, and we sequenced the whole coding regions of the deoxyguanosine kinase (dGK) and myophosphorylase (PYGM) genes., Results: Muscle biopsy specimens showed subsarcolemmal glycogen accumulation and negative histochemical reaction for phosphorylase. Liver biopsy specimens showed micronodular cirrhosis and massive mitochondrial proliferation. Biochemical analysis showed phosphorylase deficiency in muscle and cytochrome c oxidase deficiency in liver. We identified a novel homozygous missense G-to-A mutation at codon 456 in exon 11 of PYGM, as well as a homozygous 4-base pair GATT duplication (nucleotides 763-766) in exon 6 of dGK, which produces a frame shift and a premature TGA stop codon at nucleotides 766 to 768, resulting in a truncated 255-amino acid protein. Both mutations were absent in 100 healthy individuals., Conclusions: Our data further expand the genetic heterogeneity in patients with McArdle disease; confirm the strong relationship between mitochondrial DNA depletion syndrome, liver involvement, and dGK mutations; and suggest that genetic "double trouble" should be considered in patients with unusual severe phenotypes.

We describe the unreported pattern of inflammatory myopathy with abundant macrophages (IMAM) as a main differential diagnosis of postimmunization aluminum hydroxide-induced macrophagic myofasciitis (MMF). IMAM was mainly detected among patients with a dermatomyositis (DM)-like disease. Among 113 muscle biopsies from DM patients collected from 1974 to 2000, intensity of macrophage infiltration was highly variable: 41.5% (-/+); 34.5% (+); 17% (++): and 7% (+++). The 27 patients from groups (++) and (+++) had a similar pattern of macrophagic infiltration and were considered to have IMAM. They were compared to 40 MMF patients. In IMAM, macrophage infiltrates were diffuse and correlated positively with both T cell infiltrates and acute muscle fiber damage, and showed pictures of hemophagocytosis (21/27). Connective tissue structures were infiltrated by noncohesive, ribbon-forming collections of large basophilic macrophages containing no crystalline inclusions. In MMF, macrophage infiltrates were focal and formed compact well-delineated aggregates of granular PAS+ cells, loaded with crystalline aluminum hydroxide particles, in the absence of either hemophagocytosis or conspicuous muscle damage. Review of the literature indicates similarities between IMAM and "cytophagic histiocytic panniculitis" (CHP), a condition characterized by T cell-triggered macrophage hyperactivation. Both IMAM and CHP, but not MMF, may be associated with a life-threatening hemophagocytic syndrome.

Forty-three cases of peripheral neuropathy (PN) have been reported in the literature with a proven mitochondria (mt) DNA mutation, and 21 had a peripheral nerve biopsy (PNB). We studied 8 patients, 1 of whom had severe sensory PN, 3 mild PN, and 4 subclinical PN. Nerve biopsy was performed in every case; all patients showed axonal degeneration and 4 showed features of primary myelin damage. In addition, there were 2 crystalline-like inclusions in the Schwann cell cytoplasm of a patient with MERRF, and 1 in a patient with multiple deletions on the mtDNA. There are 11 cases of PNB in the literature with axonal lesions, 5 with demyelination, and 4 with mixed lesions. One PNB was not modified. A few crystalline-like inclusions were seen in 1 case of MERRF. Such inclusions were first reported in the Schwann cell cytoplasm of unmyelinated fibers in a patient with Refsum disease and were considered to be modified mitochondria. However, their mitochondrial origin remains debatable.

Introduction: It can be difficult to diagnose focal muscular disease. We report a case of crural biceps focal myositis after an insect bite., Discussion: We then discuss diagnostics of one or a small number of muscle injury. Focal inflammatory myositis has been described. We emphasize the role of pathology. In our case, pathological examination rules out inflammatory or tumoral disease and access likely toxical etiology. Muscle injury can appear, most frequently around the bite of venomous animal., Conclusion: Hymenopters are often responsible for such stings in France. Venoms are toxic for muscle cells membrane.

Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic acid-Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3-96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.

Inclusion body myositis (IBM) is a severe form of idiopathic inflammatory myopathy. A predominantly T CD8+ lymphocytic infiltrate, with focally non-necrotizing muscular fiber invasion, and rimmed-vacuoles are specific histological signs. A few cases of IBM associated with other dysimmune diseases have been reported, but only once with systemic sarcoidosis. We report three cases of muscular sarcoidosis associated with IBM. This very uncommon observation suggests that major complex of histocompatibility, soluble factors, cytokines and adhesion molecules could be involved. Our cases are a novel example of associated dysimmune diseases.

We describe three patients with macrophagic myofasciitis and inclusion body myositis. All patients fulfilled diagnostic criteria for inclusion body myositis and myopathologic criteria for macrophagic myofasciitis. In the three cases macrophagic myofasciitis complicated the evolution of a known and painless inclusion body myositis and was diagnosed in a repeated deltoid biopsy because of the appearance of myalgia during the course of inclusion body myositis in all cases. The unexpected appearance of myalgia during the course of painless inclusion body myositis must arouse the suspicion of an association of another inflammatory muscle disease, macrophagic myofasciitis.

In 1988, Kalimo et al. (Ann Neurol 23 (1988) 258)described a new type of X-linked myopathy in a Finnish family. The clinical course was characterized by slow progression of muscle weakness without loss of ambulation in childhood and no evidence of cardiac, respiratory, or central nervous system involvement. Muscle fibers were not necrotic and showed excessive autophagic activity and exocytosis of the phagocytosed material. These authors proposed the name X-linked myopathy with excessive autophagy. Subsequently, only one French family has been reported with similar clinical and histopathological data. We report here five new families with a total of eight affected boys with the same clinical and histopathological features as reported in the original families. Histopathological findings of an asymptomatic mother are also reported. Vacuolar changes in muscle fibers result both from invaginations of the sarcolemma along with a variable component of basal lamina and from an autophagic process. The complement C5b-9 membrane attack complex associated with MHC class 1 antigen and calcium deposits is involved in muscle fiber damage. Among the X-linked myopathies, the identification of this new type is of great interest because of its favorable prognosis and unique morphological findings.

Macrophagic myofasciitis (MMF), a condition newly recognized in France, is manifested by diffuse myalgias and characterized by highly specific myopathological alterations which have recently been shown to represent an unusually persistent local reaction to intramuscular injections of aluminium-containing vaccines. Among 92 MMF patients recognized so far, eight of them, which included the seven patients reported here, had a symptomatic demyelinating CNS disorder. CNS manifestations included hemisensory or sensorimotor symptoms (four out of seven), bilateral pyramidal signs (six out of seven), cerebellar signs (four out of seven), visual loss (two out of seven), cognitive and behavioural disorders (one out of seven) and bladder dysfunction (one out of seven). Brain T(2)-weighted MRI showed single (two out of seven) or multiple (four out of seven) supratentorial white matter hyperintense signals and corpus callosum atrophy (one out of seven). Evoked potentials were abnormal in four out of six patients and CSF in four out of seven. According to Poser's criteria for multiple sclerosis, the diagnosis was clinically definite (five out of seven) or clinically probable multiple sclerosis (two out of seven). Six out of seven patients had diffuse myalgias. Deltoid muscle biopsy showed stereotypical accumulations of PAS (periodic acid-Schiff)-positive macrophages, sparse CD8+ T cells and minimal myofibre damage. Aluminium-containing vaccines had been administered 3-78 months (median = 33 months) before muscle biopsy (hepatitis B virus: four out of seven, tetanus toxoid: one out of seven, both hepatitis B virus and tetanus toxoid: two out of seven). The association between MMF and multiple sclerosis-like disorders may give new insights into the controversial issues surrounding vaccinations and demyelinating CNS disorders. Deltoid muscle biopsy searching for myopathological alterations of MMF should be performed in multiple sclerosis patients with diffuse myalgias.

A large number of drugs and toxins may induce myopathic changes in several ways, they are probably more common than realized. The clinical and pathological features depend on the causative agent and on individual susceptibility to a given compound. Based on their pathologic mechanisms, there are 6 main categories of toxic myopathies: necrotizing myopathy mainly due to lipid-lowering drugs (fibrates and statines); vacuolar myopathy, usually associated with antimalarial agents; inflammatory myopathy induced by thiol derivatives; mitochondrial myopathy; steroid myopathy, and hypokaliemic myopathy. Toxic myopathies are usually reversible after discontinuation of the offending agent. Their prompt recognition may reduce their damaging effects or prevent a fatal outcome. Muscle biopsy can be very useful for the diagnosis of toxic myopathies.

Mitochondrial pathologies are a heterogeneous group of metabolic disorders that are frequently characterized by anomalies of oxidative phosphorylation, especially in the respiratory chain. The identification of these anomalies may involve many investigations, and biochemistry is a main tool. However, considering the whole set of biochemical data, the interpretation of the results by the traditionally used statistical methods remains complex and does not always lead to an unequivocal conclusion about the presence or absence of a respiratory chain defect. This arises from three main problems: (a) the absence of an a priori-defined control population, because the determination of the control values are derived from the whole set of investigated patients, (b) the small size of the population studied, (c) the large number of variables collected, each of which creates a wide variability. To cope with these problems, the principal component analysis (PCA) has been applied to the biochemical data obtained from 35 muscle biopsies of children suspected of having a mitochondrial disease. This analysis makes it possible for each respiratory chain complex to distinguish between different subsets within the whole population (normal, deficient, and, in between, borderline subgroups of patients) and to detect the most discriminating variables. PCA of the data of all complexes together showed that mitochondrial diseases in this population were mainly caused by multiple deficits in respiratory chain complexes. This analysis allows the definition of a new subgroup of newborns, which have high respiratory chain complex activity values. Our results show that the PCA method, which simultaneously takes into account all of the concerned variables, allows the separation of patients into subgroups, which may help clinicians make their diagnoses.

Unlabelled: MACROPHAGIC MYOFASCIITIS: A most unusual inflammatory myopathy, first described by Germmad had been reported with increasing frequency since 1993 in the leading French myopathology centers. We present our experience with this new disease: macrophagic myofasciitis., Clinical Features: By November 1999, 70 cases of macrophagic myofasciitis had been recorded since our first description. The first 22 patients (sex ratio M/F = 1:3) referred with the presumptive diagnosis of polymyositis (n = 11), polymyalgia rheumatica (n = 5), mitochondrial cytopathy (n = 4), and congenital myopathy or muscle dystrophy (n = 1 each). Symptoms included myalgia (91%), anthralgia (68%), marked asthenia (55%), muscle weakness (45%), and fever (32%)., Laboratory Findings: Abnormal laboratory findings included elevated CK levels (50%), markedly increased erythrocyte sedimentation rate (37%), and myopathic EMG (35%). Muscle biopsy showed a unique myopathological pattern characterized by: i) centripetal infiltration of epimysium, perimysium and perifascicular endomysium by sheets of large cells of the monocyte/macrophage lineage (CD68+, CD1a-, S100-, with a PAS-positive content; ii) absence of necrosis, of both epithelioid and giant cells, and of mitotic figures; iii) presence of occasional CD8+ T-cells; iv) inconspicuous muscle fiber damage. The picture was easily distinguishable from sarcoid myopathy and fasciitis-panniculitis syndromes. The infectious diseases know to be associated with reactive histiocytes, including Whippleís disease, Mycobacterium avium intracellulare infection and malakoplakia, could not be documented. Patients improved under corticosteroid therapy and/or immunomodulatory therapeutic, Conclusion: A new inflammatory muscle disorder, characterized by a distinctive pathological pattern of macrophagic myofasciitis is emerging in France.

X-linked myopathy with excessive autophagy (XMEA, MIM 310440) is a rare inherited mild myopathy. We have used 32 polymorphic markers spanning the entire X chromosome to exclude most of the chromosome except the Xq28 region in a large XMEA family. Using three additional families for linkage analysis, we have obtained a significant two-point lod score with marker DXS1183 (Z = 2.69 at theta = 0). Multipoint linkage analysis confirmed the assignment of the disease locus with a maximal lod score of 2.74 obtained at recombination fraction zero. Linkage of XMEA to the Xq28 region is thus firmly established. In addition, we have ruled out the Emery-Dreifuss muscular dystrophy to be allelic with XMEA by direct sequencing of the emerin gene in three of our families.

Purpose: A new type of inflammatory myopathy of unknown etiology has recently been described in France. The myopathy, called macrophagic myofasciitis, had never been described in the literature., Methods: In December 1998, 35 cases of macrophagic myofasciitis were reported, showing an increase in its incidence since the description of the first case in 1993. The first 22 cases are described., Results: The 22 patients were each referred with a presumptive diagnosis of either polymyositis (11 patients), polymyalgia rheumatica (5 patients), mitochondrial cytopathy (4 patients), or congenital myopathy or muscle dystrophy (1 patient for each). Clinical symptoms included myalgias (91%), arthralgias (68%), marked asthenia (55%), muscle weakness (45%), and fever (32%). Laboratory findings included elevated CK levels (50%) and a marked increased in the erythrocyte sedimentation rate (37%). Electromyographic recordings showed the existence of myopathy (35%). Muscle biopsy showed a unique pattern characterized by: (i) centripetal infiltration of the epimysium, perimysium and perifascicular endomysium by non epitheloid, cells of the monocyte/macrophage lineage (CD68+, CD1a-, S100-) with both large cytoplasm and PAS-positive content; (ii) absence of necrosis, of both epithelioid and giant cells, and of mitotic figures; (iii) occasional CD8+ T-cells; and, (iiii) minimal myocyte suffering. The disease symptoms were easily distinguishable from those of sarcoid myopathy and fasciitis-panniculitis syndromes. Infectious diseases known to be associated with reactive histiocytosis, including Whipple's disease, Mycobacterium avium intracellulare infection and malakoplakia, could not be documented. Patients' condition improved under corticosteroid therapy, associated or not with non-specific antibiotic therapy., Conclusion: A new inflammatory muscle disorder of unknown etiology, characterized by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France. Diagnosis is based on muscular biopsy. Numerous clinical, epidemiological and etiopathologic studies initiated by the GERMMAD (Groupe d'études et de recherche sur les maladies musculaires acquises) are in progress.

Mitochondrial oxidative metabolism in three patients with typical Menkes disease was studied. In two cases, a general decrease in all of the respiratory chain complex activities (I, II, III and IV) was observed. However, in the most severe case, these activities were entirely normal. Our results emphasize the diversity of the cellular expression of Menkes disease which can, in some cases, be associated with a mitochondrial encephalomyopathy.

Purpose: The encouraging initial results of gastrocystoplasty led us to perform it for failed bladder exstrophy closure. We assess the functional outcome of the augmented bladder and evaluate complications related directly to use of the stomach in this specific group of children., Materials and Methods: We performed gastrocystoplasty in 22 children an average of 9.5 years old with a small, poorly compliant bladder after staged reconstruction of bladder exstrophy failed. Followup ranged from 6 months to 6 years (mean 3 years)., Results: Complete urinary continence was achieved in 14 children (64%). Voiding via the urethra was possible in 13 patients (60%) but post-voiding residual urine was significant in 12. Bladder capacity increased from a mean of 77 to 270 ml. Bladder capacity decreased during followup in 3 children, requiring repeat augmentation. Six children had isolated dysuria and 2 had dysuria with hematuria. Perforation of the gastric patch and a bleeding gastric ulcer occurred in 1 patient each., Conclusions: The disadvantages of gastrocystoplasty outnumber its advantages after failed bladder exstrophy closure. Urethral sensation makes dysuria a major discomfort. Safety is not optimal, since perforation may occur. Voiding is not efficient because gastrocystoplasty provides continence only when it is associated with intermittent catheterization. Bladder capacity is insufficiently augmented and inconsistent during followup. We believe that the use of gastrocystoplasty in cases of failed bladder exstrophy closure should be reconsidered.

Aims: We report three cases of skeletal muscle regeneration, of which two mimicked a small round cell tumour, especially a rhabdomyosarcoma., Methods and Results: One case presented as an intramuscular mass, located in the right quadriceps of a 12-year-old male; the second patient was a 25-year-old football player who complained of painful left peroneus muscles; the third patient was a 22-year-old male who underwent an amputation of the right thigh 5 days after right leg amputation due to limb crush. Histologically, muscle biopsy specimens showed a proliferation of small round cells, either infiltrating the striated muscle in a diffuse manner or growing within and around necrotic myofibres. Immunohistochemically and ultrastructurally, the cellular population was composed of two types of cells: phagocytic cells the nuclei of which occasionally showed a wreathlike arrangement around necrotic myofibres resulting in structures resembling Langhans-type multinucleated giant cells, and proliferating satellite cells showing enlarged nuclei, prominent nucleoli, mitotic figures, myogenic differentiation and fusion features in order to form regenerating myotubes., Conclusions: Muscle regeneration is a benign process that may occasionally mimic a small round cell proliferation resembling a lymphoma or an alveolar rhabdomyosarcoma with which it should not be confused.

Background: An unusual inflammatory myopathy characterised by an infiltration of non-epithelioid histiocytic cells has been recorded with increasing frequency in the past 5 years in France. We reassessed some of these cases., Methods: We did a retrospective analysis of 18 such cases seen in five myopathology centres between May, 1993, and December, 1997. The myopathological changes were reassessed at a clinopathology seminar., Findings: Detailed clinical information was available for 14 patients. The main presumptive diagnoses were polymyositis and polymyalgia rheumatica. Symptoms included myalgias in 12 patients, arthralgias in nine, muscle weakness in six, pronounced asthenia in five, and fever in four. Abnormal laboratory findings were occasionally observed, and included raised creatine kinase concentrations, increased erythrocyte sedimentation rate, and myopathic electromyography. Muscle biopsy showed infiltration of the subcutaneous tissue, epimysium, perimysium, and perifascicular endomysium by sheets of large macrophages, with a finely granular PAS-positive content. Also present were occasional CD8 T cells, and inconspicuous muscle-fibre damage. Epithelioid and giant cells, necrosis, and mitotic figures were not seen. The images were easily distinguishable from sarcoid myopathy and fasciitis-panniculitis syndromes. Whipple's disease, Mycobacterium avium intracellulare infection, and malakoplakia could not be confirmed. Ten patients were treated with various combinations of steroids and antibiotics; symptoms improved in eight patients, and stabilised in two., Interpretation: A new inflammatory muscle disorder of unknown cause, characterised by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France.

Micturition disorders were studied retrospectively in a series of 165 children over a period of 15 years. Among patients without lesions of the upper tract at the time of diagnosis (group A, n = 131), 18 (14%) had persistent nocturnal and diurnal enuresis: one urethral stenosis and six vesicoureteric reflux required surgery; three experienced persistent pollakiuria and enuresis. Among patients with upper urinary tract damage at the time of diagnosis (group B, n = 34), seven presented with recurrent urinary tract infection, five with nocturnal and diurnal enuresis and three with urolithiasis. In the long term, only 52% of them had normal renal function and two were successfully transplanted. Micturition disorders following treatment of posterior urethral valves are frequent and usually related to the so-called valve bladder syndrome. Iatrogenic complications and mortality rate have dramatically decreased during the recent years but long-term renal function impairment remains the most critical problem.

Muscle biopsy is a simple procedure of great diagnostic interest when correct processing is obtained. Specimens for molecular genetics are very important. Paraffin embedded material is not sufficient in most of the cases except in some inflammatory processes. Histochemical techniques on frozen material are of major interest. Immunohistochemistry and electron microscopy can also be used. The aim of this paper is to describe the procedure of the muscle biopsy, the various techniques and the possible artefacts.

Pulmonary blastoma is a rare malignant tumor. A new case is reported in a 3 years 6 month-old girl. An apparent clinical remission was first obtained after a surgical treatment followed by a conventional chemotherapy during six months. Afterwards the persistence of a microscopic residual pulmonary disease lead us to deliver successfully an intensive chemotherapy followed by autologous peripheral blood stem cells reinjection. The child remains disease free 12 months after graft. Problems set by the histogenesis of this tumor, its unspecific clinical and paraclinical features and the role of conventional and intensive chemotherapy followed by autologous bone marrow transplantation are discussed on the basis of a review of 50 cases in the literature.

A wedge-shaped segment of stomach based on the right gastroepiploic artery was used for bladder augmentation in 11 patients. Initial diagnosis in these 11 patients was bladder exstrophy. Indications for the use of stomach in bladder reconstruction were important bilateral upper tract deterioration in 10 patients, dederivation in 1. A continent appendicostomy (Mitrofanoff) has been performed in all patients. In post-operative follow-up (average 24 months), all patients have stable upper tract X-rays and stable or improved renal function. All patients require intermittent clean catheterization, 8 are totally continent, 2 are partially continent, 1 patient is still incontinent. No serious digestive problem was encountered. The increase in bladder capacity was 300 to 500% after 6 months. Mucus production is reduced relative to other intestinal segments and the patients require no bladder irrigation. The authors recommend the use of stomach for urinary tract reconstruction in compromised patients.

A new regimen for postoperative analgesia after thoracic surgery is proposed. Eight children received an interpleural infusion using bupivacaine 0.1% in a regimen from 0.5 ml.kg-1.h-1 up to 1 ml.kg-1.h-1, for 48 h according to the pain scores. The plasma levels after 24 h and 48 h were measured as well as the pleural level and in two patients the free fraction of plasma bupivacaine and the plasma PPX (a metabolite of bupivacaine) and one patient the orosomucoid (main plasma protein involved in bupivacaine protein binding) were also measured pre and postoperatively. The results shows the safety of such a regimen, for two days of postoperative analgesia.

Muscular hypertrophy, rarely reported in muscular sarcoidosis, is usually associated with the myositic, myopathic and nodular types. We report a case with an isolated localised muscular hypertrophy simulating a tumor formation developed after repetitive efforts, in a familial context of sarcoidosis. MRI shows muscular high intensity lesions in the thighs and calves, and after treatment, central areas of low intensity signal. Muscular biopsy confirms diagnosis of sarcoidosis. Gallium-67 scintigraphy shows systemic extension of disease. This case highlights the usefulness of recent imaging techniques in diagnostic strategy and follow up.

A girl with severe Becker muscular dystrophy and apparently normal chromosomes had a heterozygous deletion for exons 51, 52, and 53 of the dystrophin gene. This deletion was transmitted by her mother, who was unaffected. To differentiate the normal and the deleted X chromosomes, fluorescence in situ hybridization (FISH) was applied to metaphase chromosomes, using probes for both exons 51 and 52, which are only 388 and 113 base pairs long, respectively. FISH signals were observed in one or both chromatids of one chromosome, but never on both chromosomes, suggesting the lack of hybridization on the deleted X chromosome. Using 5-bromodeoxyuridine incorporation to differentiate the late (inactive) and the early replicating (active) X chromosomes, 77% of the signals were observed on the active X chromosomes in the mother. This percentage was only 18% in the daughter, suggesting that skewed inactivation of the X chromosomes was responsible for the phenotypic differences.

Mitochondrial cytopathies are multisystemic disorders of extremely variable expression due to a deficiency in oxidative phosphorylation. Cases have recently been reported in which fatal liver failure with neonatal onset was the major clinical and biochemical syndrome. In this series we reviewed the liver histology of 10 such patients who died in the first weeks of life (from 3 days to 6 mo). In six cases the diagnosis was confirmed by study of the mitochondrial respiratory chain in the muscle, liver or both; in the other four, appropriate tests were not available for diagnosis but symptoms were identical and all other diagnoses were ruled out. In all 10 cases we noted significant steatosis, mostly microvesicular; widespread hepatocytic, canalicular and bile duct cholestasis with bile thrombi and cholangiolar proliferation; and different degrees of hepatosiderosis and glycogen depletion. Fibrosis took varying forms: perisinusoidal, periportal with the formation of septa, even precirrhosis. In the two cases of infants who died, one at 5 and one 6 mo, micronodular cirrhosis was also present. Mitochondria, either densely or loosely packed, were abnormal-pleiomorphic with few or no cristae and a granular fluffy matrix. Dense, large granules were seen in two cases. The association of neonatal liver failure and hyperlactacidemia should lead to immediate examination of the respiratory chain. The expression of this mitochondrial cytopathy can be lethal, associated with severe liver damage due to the deficiency in oxidative phosphorylation.

This article reports a new MERRF family. The mother, regarded as suffering from Ramsay-Hunt Syndrome, and her three daughters, had the same clinical pattern: myoclonic epilepsy and ataxia. Two daughters were studied on morphological, biochemical and molecular genetic levels. Muscle biopsies showed ragged-red fibres and mitochondrial vasculopathy. Arterioles were strongly SDH-reactive and COX-negative. By electron microscopy, abnormal mitochondria were observed in skeletal muscle fibres, in smooth muscle fibres of intramuscular vessels and in sweat gland epithelium. The study of the respiratory chain showed complex IV and I + IV deficiency, respectively. Mitochondrial tRNA (lys) mutation at position 8344 was pointed out as previously reported in the MERRF syndrome.

We report a case of mitochondrial myopathy (MM), assessed by histological and biochemical studies. This illness was diagnosed in a 69-year-old patient with myocardiopathy revealed by ventricular arrhythmias. The originality of this case lies in the patient's age, the mode of onset and the biochemical features (i.e. normal mitochondrial enzymatic complexes but very low respiration when using glutamate as a substrate).

The onset of severe muscle cramps in the course of road racing led a champion to undergo a muscle biopsy. Fuscinophilic deposits were detected around muscle cell fibers together with a few PAS positive deposits. These findings were related to the accumulation of abnormal mitochondria and glycogen granules. The subsequent study of the mitochondrial respiratory chain did not reveal any modification and so ruled out a genuine mitochondrial myopathy. Such mitochondrial modifications are probably related to the onset of muscle cramps, but no metabolic disturbance could be found to account for these two phenomena.

We report a series of 46 patients (32 women and 14 men) with limb-girdle syndrome. After reappraisal, another diagnosis was made in 10 of them. Becker's muscular dystrophy was the most frequent cause among men (near 50 p. 100). A Duchenne muscular dystrophy manifesting carrier was discovered among 13 reevaluated women. Among the 36 cases (29 women and 7 men) without any defined etiology, 29 were without any other known familial history. Fifteen of these women had similar clinical findings: incipient weakness in the pelvic girdle and onset of symptoms most often in the forties. In these cases serum creatine kinase activity was normal or slightly elevated, and muscle biopsy showed non-specific patterns. "Late onset muscular dystrophy in females" should be reevaluated.

Mitochondrial cytopathies are multisystemic diseases of extremely variable expression caused by a deficiency in oxidative phosphorylation. Only five cases of neonatal liver failure in the context of mitochondrial cytopathy have been reported, with incomplete morphological data of the liver in three. In the case presented here, ascites had been diagnosed prenatally and liver failure was particularly severe (factor V less than 15% with fatal coma the fourth day). Histologically there were incomplete cirrhosis, microvesicular steatosis, major canalicular cholestasis with proliferative neocholangioles, and bile duct thrombi. There were also some iron pigments in the periportal area and partial glycogen depletion. By electron microscopy, mitochondria in numerous hepatocytes appeared abnormal with occasional cristae in a fluffy matrix, some containing dense inclusions. Study of respiratory chain activity showed a defect in cytochrome c oxidase (complex IV), revealed by oxygraphic measurement on fresh muscle biopsy and confirmed by spectrophotometric enzymatic assays performed on muscle and liver homogenates. The association of neonatal liver failure with hyperlactacidemia warrants investigation into a deficiency in oxidative phosphorylation.

Respiratory parameters of skeletal muscle were determined in permeabilized muscle fibers by adapting a technique described by Veksler et al. for cardiac fibers (Biochim Biophys Acta, 892:191-196, 1987). This method consists of the permeabilization of muscle fibers by saponin by allowing respiratory substrates and inhibitors to reach the mitochondria. In this way, the mitochondria may be studied inside the fibers as if they were isolated. We have verified, using various techniques, that the mitochondria remain intact during this procedure. This method has been applied to the study of six newborn infants for whom a diagnosis of a mitochondrial defect was suspected. In all cases, the defect was to be found on the permeabilized fibers, and this was confirmed by an enzymatic study. The advantage of this new method, associated with the measurement of the enzymatic activities on a crude homogenate, is to enable a simple and rapid diagnosis on a small amount of sample without damaging the mitochondria during the isolation procedure.

We reviewed the cases of 95 children with duplex ureteroceles treated in this department over an 18-year period. There were 101 ureteroceles (6 bilateral). Diagnosis and treatment were analyzed. Special attention was paid to newborns screened in utero. We always strove to preserve functional renal tissue whenever possible. In keeping with this goal, three surgical techniques were used: (1) upper pole heminephrectomy; (2) ureterocele excision, bladder neck reconstruction, and ureter reimplantation with or without cutaneous ureterostomy of the upper pole ureter; and (3) endoscopic ureterocele incision. Follow-up studies using x-ray and radionuclide imaging demonstrated satisfactory renal function in 86.6% of patients. These findings support a conservative approach to ureteroceles using endoscopic ureterocele incision as the primary treatment. Lower urinary tract reconstruction may be associated in cases involving urinary tract infection, obstruction or incontinence. Upper pole heminephrectomy should be performed only after functional evaluation following ureterocele incision or cutaneous ureterostomy.

A 21-year old women with rhizomelic muscular deficit and signs of hypercapnia developed acute respiratory failure. Laboratory tests revealed high creatine kinase activity, and electromyograms showed myogenic patterns with a few myotonic discharges. Biopsy of the quadriceps muscle elicited major vacuolar myopathy with glycogen overload. Acid maltase activity was undetectable in muscular tissue. After 7 months on high-protein diet (1540 calories, 37% proteins) there was no clinical or biochemical improvement. The other published cases of acid maltase deficiency treated with high-protein diet are discussed.

In a family 6 members in 3 generations were affected by centronuclear myopathy (CNM) of autosomal dominant inheritance. The apparent onset was in the early forties and the disease progressed slowly. Limb weakness was predominant. Strabismus was present in 5 cases and calves hypertrophy in 3. Serum creatinine kinase was always within the normal range. In one case myotonic bursts were found at electromyography. In 2 cases brain stem auditory evoked potential studies demonstrated abnormal prolongation of interpeak latencies I-III and favoured subclinical nervous system involvement. Muscular biopsies showed typical features of centronuclear myopathy with 50 to 80% central nuclei. In two cases immunocytochemical labelling of dystrophin showed staining in the sarcoplasm in favour of an arrest in the morphogenesis of developing myofiber. Others families with autosomal dominant CNM in the literature and also some sporadic adult cases had similar clinical features.

There is currently widespread enthusiasm for abdominal wall reconstruction in patients with the prune belly syndrome. We have devised an operation that appears to offer some advantages over those proposed by Ehrlich and Randolph. The technique preserves the umbilicus, and thickens and strengthens the anterior abdominal wall. By narrowing the waist, it also produces a better cosmetic appearance. After full thickness resection of a varying amount of skin from the central abdomen, the anterior wall is sutured in double-breasted fashion, thus, preserving all vascularization and the umbilicus. Since 1969 we have successfully performed this procedure on 9 prune belly patients including 1 girl. The results were excellent in terms of duration and cosmetic appearance.

Defecography is a useful paraclinical examination to explore disturbances of continence or defecation. The purpose of this study was to present a simplified defecography technique and assess its validity in subjects without defecation problems (n = 10) and in patients complaining of idiopathic chronic constipation (n = 35). The anorectal angle at rest (RAA) and when straining at stool was not significantly different in constipated patients and in controls. Defecography often gave abnormal results. Anterior rectocele was found in almost 50 percent (17/35) of constipated patients and in 20 percent (2/10) of controls (P less than 0.05). None of the patients had posterior rectocele. Persistent imprint of the puborectal muscle during straining was present in 36 percent (9/35) of constipated patients and in 10 percent (1/10) of controls (NS). The imprint was not always associated with closure of the RAA between rest and straining; this closure was never found in controls but was observed in 6 out of 17 constipated patients (35 percent; P less than 0.05). Perineal descent (PD) varied from 0.6 to 3.7 cm (mean +/- s.e.m.: 2.0 +/- 0.63 cm) in controls, as against 0.6 to 7.9 cm (mean +/- s.e.m.: 2.7 +/- 0.45 cm) in constipated patients. In 24 percent of the constipated patients PD was greater than 3.7 cm (the maximum value recorded in controls). All constipated patients with closure of the RAA during defecation had a PD of less than 1 cm, thus confirming the concept of "pelvic floor muscle hypertonia". Disorders of rectal statics are more frequent in subjects with constipation, but their significance is varied. Some abnormalities could be the cause of constipation (e.g. anismus) and others its consequence (anterior rectal prolapse, anterior rectocele, PD).

Ten cases of oculopharyngeal muscular dystrophy (OPMD) were examined ultrastructurally. Two very different types of filamentous inclusions were observed: (1) Nuclear inclusions composed of 8.5 nm external diameter tubular filaments organized in palisades and similar to those described by Tomé and Fardeau (1980). They have not yet been reported in other muscle diseases. Their presence in 100% of our cases confirms they are the morphological hallmark of OPMD. (2) 16-18 nm external diameter tubular filaments. These were similar to the inclusions observed in inclusion body myositis (IBM) and morphologically very different from the first type. They were randomly dispersed or arranged in bundles near cytoplasmic debris and whorls of membranes. They were found in cytoplasm. Only once were they observed in a nucleus. These inclusions have been described in IBM but also in other diseases. They were found in 80% of our OPMD cases.

The authors report the case of a 14-year-old boy who presented with shunted growth and low weight gain, asthenia with fatiguability on effort, clinical signs of myopathy, ataxia, epilepsy, deafness, loss of visual acuity and reduced intellectual capacities. Muscle biopsy revealed numerous ragged-red fibres and mitochondrial anomalies at ultrastructural examination. Cerebral biopsy showed spongiform changes. Both muscular and cerebral biopsies showed vascular lesions: swollen endothelial cells. Mitochondria increased in number with concentric whorls of cristae were observed in pericytes and smooth muscle cells. This mitochondrial vasculopathy could explain the neurological symptoms.