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Item does not contain fulltext Mitochondria are bacteria-like semi-autonomous intracellular organelles that function as the powerhouses of eukaryotic cells. Inactivation or destruction of these organelles may have far-reaching consequences regarding the viability of the cells and thus of tissues, organs and finally even the body. Since mitochondria resemble (degenerated) bacteria, we have extrapolated from both cytological and microbiological facts the existence of various (kinds of) mitochondrion-specific microbial pathogens, i.e., pathogenic micro-organisms that may damage or destroy the mitochondria from within. These mito-pathogens may include mitoviruses, mitoviroids and mitobacteria. Although these mito-pathogens have not yet been demonstrated in humans, their theoretical degenerative effect regarding energy production from energy-rich substrates, such as carbohydrates and fats, might explain diseases that have not yet been understood, such as prion diseases and post-traumatic muscle dystrophy. Therefore, these kinds of micro-organisms should be kept in mind.

Lengthening during contraction allows muscles to develop force well above the levels reached in isometric conditions. Such enhanced performance has, however, a negative counterpart: damage which is revealed by pain (DOMS), structural and ultra-structural alterations and reduced ability to develop force (Asmussen, 1952). The phenomenon has been demonstrated in vitro and in vivo, in amphibian as well as in mammalian muscles and two main factors have been identified as determinants of eccentric contraction-induced damage: myofibrillar disorganization (Z line streaming and sarcomere length heterogeneity) (Allen, 2001) and calcium homeostasis alteration, possibly related to T tubule disruption (Warren et al. 1993). About 15 years ago Petrof and coworkers showed that mdx dystrophic muscles are highly sensitive to eccentric contraction damage as they show greater loss of force and cellular damage, indicated by sarcolemmal disruption and procion orange penetration, than wild-type muscles (Petrof et al. 1993). Although only sparse evidence is available, the phenomenon seems to be specific to mdx mice and not present in other murine models of muscular dystrophy (Head et al. 2004). Since Petrof's paper was published, many studies aimed to identify the mechanism responsible for the extra damage of dystrophin-lacking fibres exposed to eccentric contractions. It was assumed that the sarcolemma, made fragile by the lack of dystrophin, was easily broken by the intense mechanical strain generated by eccentric contraction. This led to the ‘delta lesions’ early observed in DMD fibres (Pestronk et al. 1982), which were sufficient to give access to large extracellular molecules. Calcium influx and subsequent increase of intracellular free calcium were considered the trigger for degeneration and death of the muscle fibres. The scenario was considerably shifted by more recent studies which suggested that calcium entry could follow a more physiological pathway. The involvement of channels of the TRPC family, which support both stretch activated and store operated calcium influx, was demonstrated (Vandebrouck et al. 2002) and inhibitors of the stretch-activated channels were proved sufficient to control the calcium influx (Yeung et al. 2005). Thus, calcium influx might be a cause and not a direct effect of the membrane tears, and the activation of a relatively slow intracellular mechanism is needed to make the connection (Yeung et al. 2005). The paper published by Whitehead et al. (2008) in this issue of The Journal of Physiology unveils such a connection. Some years ago it was shown that mdx muscle fibres are more susceptible to ROS damage (Rando et al. 1998) and show signs of increased lipid and protein oxidation in spite of the enhanced expression of antioxidant enzymes (Hauser et al. 1995). Whitehead and coworkers demonstrate that an active antioxidant treatment based on N-acetylcysteine (NAC), which is membrane permeant and known to be active in muscle fibres, significantly reduces the impact of eccentric contraction on mdx muscle fibres when given either in vivo or in vitro. Thus, ROS may represent the missing intracellular link between calcium entrance and membrane tears. Two important questions follow: where are ROS produced and what are their targets?Whitehead et al. (2008) suggest that the two main sites of ROS production are mitochondria, whose activity is stimulated in response to increase of intracellular calcium, and NADPH oxidase. The targets of ROS are, obviously, many, but one is of special interest for the fate of dystrophic fibres. Sarcolemma can be destabilized by the lack of β-dystroglycan (BDG), which is essential for the structure of costamere, the skeleton of the muscle membrane. Src kinase activated by ROS (Chen et al. 2005) phosphorylates BDG leading to its internalization. This process is counteracted by dystrophin and utrophin and enhanced by caveolin 3. Besides, lipid peroxidation and membrane protein oxidation might be involved. The proposed interpretation receives strong support from the results of the NAC treatment, which prevents the eccentric contraction damage in mdx, but not in wild-type, muscles, restores the presence of BDG and decreases the amount of caveolin 3. All together, this represents a substantial contribution to maintaining the structural and functional integrity of the membrane. Whether the mechanism outlined above is the only one responsible for the triggering of degenerative processes in muscles lacking dystrophin is still to be defined, but it may represent, in any case, a significant component of the worsening of the pathological phenotype. As suggested by the experiments reported by Whitehead and coworkers the control of oxidative stress may also become an important avenue to study therapies to improve the dystrophic muscle conditions.

Congenital muscle dystrophy (CMD) is a heterogeneous group of autosomal recessive myopathies. It is known that CMD may affect the central nervous system (CNS). Some authors have shown that merosin-negative CMD patients may have encephalic metabolic disturbances. In order to study metabolic changes within the brain, the authors performed a magnetic resonance spectroscopy (MRS) study in a 1-year-old girl with merosin-positive CMD (MP-CMD). MRS of brain demonstrated that NAA/Cr ratio was decreased (1.52), while Cho/Cr ratio was increased (1.78). These findings suggest that metabolic changes in CNS can also be found in patients with MP-CMD.

Titelblatt, Inhaltsverzeichnis, Zusammenfassung, Danksagung, Erklärung Einleitung Material und Methoden Ergebnisse Diskussion Literaturverzeichnis, Die Duchenne Muskeldystrophie (DMD) gehört zu den häufigsten erblichen Muskeldystrophien im Kindesalter. Gegenwärtig werden die Substitution von Dystrophin oder ähnlichen Proteinen sowie die Korrektur der Mutation und damit die Wiederherstellung der Dystrophinexpression als gentherapeutische Strategien verfolgt. Jedoch führt sowohl die Herstellung der Dystrophinexpression als auch die Verwendung von viralen Transfersystemen im adulten Organismus zu Reaktionen des Immunsystems. Zudem wird eine autologe ex vivo Therapie durch eine limitierte Zahl an Myoblasten eingeschränkt. Fetale und Dystrophin-Downstream Konzepte könnten Probleme der genannten Strategien umgehen bzw. sinnvoll unterstützen. Expressionsuntersuchungen in Dystrophin negativen (Dys-) Muskelzellen zeigten Veränderungen in Genen für Zellwachstum und Differenzierung. So wiesen Biopsien von DMD-Patienten ein erhöhtes Niveau an p21 mRNA auf, einem Cyklin-abhängigen Kinase-Inhibitor, der hoch reguliert das Fortschreiten der Zellen von der G1 zur S1 Phase im Zellzyklus und somit die Zellteilung inhibiert. Ein erhöhtes Niveau von p21 schränkt somit die Zielzellen für eine autologe ex vivo oder in vivo Gen- und Zelltherapie ein. Die Reduktion von p21 würde die Möglichkeit bieten das Reservoir an Myoblasten zu erhalten oder wiederherzustellen. In der vorliegenden Arbeit erfolgte die Etablierung der p21 Inhibition in vitro durch RNA-Interferenz. Hierfür wurden optimale Transfektionsbedingungen und funktionelle siRNAs ermittelt. Die effektiven siRNAs wurden in einem lentiviralen Vektorsystem verwendet, um einen möglichst vollständigen und stabilen p21 knockdown zu erzielen. Dies geschah für primäre humane Myoblasten und für murine C2C12 Zellen, um den Effekt der p21 Inhibition auf die Proliferation zu untersuchen. Die Austestung an murinen Zellen erlaubt die Entwicklung eines Systems für einen in vivo Versuch am mdx-Mausmodell. Zwei in humanen Myoblasten wirksame siRNAs gegen p21 kamen an Dys- Zellen zum Einsatz. Die siRNA induzierte p21 Proteinreduktion betrug 72 Stunden nach Transfektion 29% bis 78%. Die p21 Proteinreduktion resultierte in einer Proliferationssteigerung von 11% bis 47% gegenüber unbehandelten Kontrollen. Die Expression von siRNA im lentiviralen Vektor führte zu einer nachhaltigen p21 Proteinreduktion von 70% fünf Wochen nach Infektion in Zellen eines DMD Patienten. Die Proliferation der infizierten Zellen stieg um 127%. Wiederholte Infektionen von Zellen eines anderen Patienten zeigten einen Proliferationsanstieg von 35% bis 63%. Die Unterschiede in der p21-Reduktion und der Proliferationssteigerung weisen auf eine hohe Varianz des siRNA Effektes hin. Hierbei können Unterschiede im Integrationsort des lentiviralen Vektors und individuelle Schwankungen in der p21 Basisexpression eine Rolle spielen. Die p21 Inhibition verhinderte eine vollständige Differenzierung. Für murine Zellen wurde ebenfalls eine siRNA identifiziert, die nach transienter Transfektion zu einer p21 Inhibition von 61% nach 48 Stunden führte. Die abgeleitete, viral exprimierte shRNA erzielte jedoch nur eine Reduktion von 30% gegenüber Kontrollen. Die Ergebnisse dieser Arbeit zeigen, dass eine stabile p21 Reduktion mittels viral vermittelter RNA- Interferenz in der Lage ist die Proliferation von Dys- Zellen zu steigen. Damit könnte der stetige Verlust von Myoblasten bei DMD Patienten eingeschränkt werden, was zum Erhalt der Zielzellen für eine Gen- und Zelltherapie führt. Weiterführende Arbeiten zur Regulation der p21 siRNA Expression müssen jedoch eine Redifferenzierung der Myoblasten sicherstellen und sich dem Infektions-bedingten Zellverlust stellen. Während eine p21 Reduktion alleine keine Ursache für eine Onkogenese zu sein scheint, müssen verbesserte retrovirale Systeme Integration-bedingte Risiken minimieren., Duchenne Muscle Dystrophy (DMD) is one of the most common heritable muscle disorders in childhood. Dystrophine substitution or gene fixing approaches to restore dystrophine expression are currently investigated as gene therapeutic strategies. But there are still obstacles to overcome like immune response to the re-established dystrophine expression as well to viral vector systems. And autologous ex vivo therapies are limited due to the small amount of available target cells. Fetal- or dystrophine-downstream concepts could bypass or assist some problems of these strategies. Comprehensive studies on expression of dystrophine negative (dys-) myoblasts showed altered expression of genes involved in cell proliferation and differentiation. Biopsies of DMD patients showed an increased level of cyclin dependent kinase inhibitor p21 mRNA compared to dystrophine positive controls. P21 regulates the G1 S1 progression within the cell cycle. An elevated level on p21 inhibits cell proliferation and limits the potential target cells for an autologous ex vivo as well as in vivo gene or cell therapy. Therefore a reduction in p21 could help to maintain or restore the reservoir of myoblasts. In the present study a p21 inhibition by RNA-Interference was established. Optimal transfection parameters were determined and potent p21 siRNAs were identified. The influences on cell proliferation were investigated. Effective siRNAs were used in a lentiviral vector system to achieve a long lasting, inducible and complete p21 knockdown. This was done in primary human myoblasts as well as in murine c2c12 cells. This parallel approach provides the opportunity to use this strategy in vivo in the mdx mouse model. Two effective siRNAs against human p21 were used on primary dystrophine negative myoblasts. P21 protein was reduced by 29% to 79% after 72 hours after transfection and resulted in an increase in proliferation by 11% to 47% compared to untreated controls. The siRNA expressed by a lentiviral vector lead to a prolonged reduction of p21 protein by 70% of myoblasts from a dys- patient five weeks after infection. The proliferation was elevated by 127%. Infection of myoblasts from a second patient resulted in a protein reduction by 35%-63%. The p21 knockdown prevented also a complete differentiation of myoblasts. Differences in p21 basis expression, or different integration sites of the lentiviral vector could be the reason for observed variances in the effect of siRNA inhibition. The p21 knockdown prevented also a complete differentiation of myoblasts. Additionally effective siRNAs for tests on murine myoblasts were identified. After transient transfection p21 protein was reduced by 61% after 48 hours. The same siRNA expressed by a lentiviral vector showed a decrease of p21 protein by only 30% compared to untreated controls. Differences in p21 basis expression, or different integration sites of the lentiviral vector could be a reason for the observed variances in the effect of siRNA inhibition. The present study shows that a stable p21 inhibition by RNA interference can lead to an increased proliferation of dys- myoblasts. This could prevent the continuous loss of myoblasts and preserve cells for an additional gene and cell therapy. Following studies which focus on regulation of siRNA expression should assure redifferentiation of treated myoblasts. Although the loss of p21 alone seemed no cause of oncogenesis, retroviral vector systems have to be improved to minimize the risk of oncogenesis by random integration.

The myocardial performance index (MPI) was assessed in 30 patients with limb girdle muscle dystrophy (LGMD) with a normal left ventricular ejection fraction (greater than 50%), as well as in 30 age- and sex-matched healthy adults with a left ventricular ejection fraction greater than 50%. MPIs derived by pulsed-wave Doppler and tissue Doppler were also compared. The MPI was 0.37±0.09 in the LGMD patients and 0.29±0.09 in the control group (P=0.003). These data show that patients with LGMD have occult cardiac dysfunction as evidenced by a higher MPI than the controls. There was good agreement between the MPIs measured by pulsed-wave Doppler and tissue Doppler methods in these patients.

We present a case of severe optic neuropathy following linezolid treatment, which led to complete irreversible blindness, in a patient with progressive muscular dystrophy, treated with linezolid for 16 days for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Interruption of antibiotic therapy did not lead to remission of ocular symptoms. Administration of linezolid may lead to severe neuropathy even in the case of short-term treatment. Copyright © 2006 John Wiley & Sons, Ltd.

Efficient delivery of cells to target tissues is a major problem in cell therapy. We report that enhancing delivery of mesoangioblasts leads to a complete reconstitution of downstream skeletal muscles in a mouse model of severe muscular dystrophy (α-sarcoglycan ko). Mesoangioblasts, vessel-associated stem cells, were exposed to several cytokines, among which stromal- derived factor (SDF) 1 or tumor necrosis factor (TNF) α were the most potent in enhancing transmigration in vitro and migration into dystrophic muscle in vivo. Transient expression of α4 integrins or L-selectin also increased several fold migration both in vitro and in vivo. Therefore, combined pretreatment with SDF-1 or TNF-α and expression of α4 integrin leads to massive colonization (>50%) followed by reconstitution of >80% of α-sarcoglycan–expressing fibers, with a fivefold increase in efficiency in comparison with control cells. This study defines the requirements for efficient engraftment of mesoangioblasts and offers a new potent tool to optimize future cell therapy protocols for muscular dystrophies.

In skeletal muscle, release of calcium from the sarcoplasmic reticulum (SR) represents the In skeletal muscle, release of calcium from the sarcoplasmic reticulum (SR) represents the major source of cytoplasmic Ca2+ elevation. SR calcium release is under the strict command of the membrane potential, which drives the interaction between the voltage sensors in the t-tubule membrane and the calcium-release channels. Either detection or control of the membrane voltage is thus essential when studying intracellular calcium signaling in an intact muscle fiber preparation. The silicone-clamp technique used in combination with intracellular calcium measurements represents an efficient tool for such studies. This article reviews some properties of the plasma membrane and intracellular signals measured with this methodology in mouse skeletal muscle fibers. Focus is given to the potency of this approach to investigate both fundamental aspects of excitation-contraction coupling and potential alterations of intracellular calcium handling in some muscle diseases.

Non-invasive measurements and quantitative evaluation of the natural course of disease need to be established in anticipation of replacement therapy in Duchenne muscular dystrophy (DMD). A cohort of 23 DMD boys (6–18years, 14 non-ambulant), were enrolled specifically to characterize disease progression of upper limbs, to be targeted in future therapeutic trials. Prior studies in the GRMD canine model showed that Nuclear Magnetic Resonance imaging (NMRI) and phosphorous spectroscopy (NMRS) could provide quantitative indices which graded with therapeutic dose. A similar approach was implemented in patients, who were examined in a 3T-60cm Siemens Magnetom TRIO system, with the arm along the body. The two arms were examined in separate sessions, to be repeated yearly, comprising NMRI (measurement of T2 of muscle water, and of fat fraction by 3-point Dixon imaging) and NMRS of phosphate metabolites. Each item lasted ∼20min. Twelve indices were analysed: –2 in NMRI: %fat signal (%F), muscle water T2 (deconvoluted from fat) –10 in NMRS: 8 ratios of metabolites combining: ATP, phosphocreatine, phospho mono- and di-esters and two pools of inorganic phosphate: cytosolic (Pia) and an anomalous alkaline pool present in dystrophic muscle (Pib), and 2 indices for respective pH values. T2 was above laboratory norms in 15% of cases, % F exceeded 10% of signal in 70% of cases and correlated to patient age ( R =.58, P R =.38 to .46, P F , ( R =.46 to .77, P Quantitative NMRI and NMRS provided a variety of indices which were abnormal in forearms of DMD patients, covering a broad range of fat infiltration, and metabolic abnormalities which graded together and with patient age and could provide biomarkers of therapeutic efficacy.

Summary The lesser diameter of the fibers, separately of type 1 and type 2 fibers, and the capillary density evaluated as number of capillarieslarea and number of capillaries/fiber were quantitatively estimated in muscle biopsies from 12 patients with systemic sclerosis. Nine patients with polymyositis or rheumatoid arthritis and six patients with muscle dystrophy and neurogenic atrophy served as controls. The results showed that patients with systemic sclerosis had low values of the lesser diameter of the fibers. This reduction was most obvious in type 2 fibers. The capillaries were also significantly reduced when compared with the control groups. When considering the capillaries1fiber ratio, seven out of eight patients with values lower than 0.7 belonged to the systemic sclerosis group. In systemic sclerosis the capillary density values were not significantly correlated with those of the lesser diameters of the fibers.

Validation studies of bioelectric impedance analysis (BIA) were performed in children with obesity, Duchenne muscle dystrophy and juvenile rheumatoid arthritis. BIA allowed an accurate assessment of total body water in all groups (CV from 4.1 to 5.1%). However, the prediction of extracellular water by BIA was not always satisfactory (CV from 8.5 to 12.5%), being better in the groups of children with the lowest variability in body water distribution.

The aim of this study was to improve the specificity of cationic lipid-based vectors. We started assembling from scratch particles consisting of commercially available cationic lipid reagents. The lipid particles were decorated with peptide fragments of the neuronal cell adhesion molecule (NCAM) which mimic NCAM-homophilic binding. Regenerating muscle fibres, as they appear e.g. in the pathological state of Duchenne Muscle Dystrophy, express this satellite cell marker NCAM.

In a 57-yr-old female with dystrophia myotonica, attempts to reverse residual non-depolanzmg block with neostigmine 1.0 mg were only partially effective and the administration of a further dose (0.5 mg) produced long-lasting muscle weakness. The train-of-four response of this patient resembled that of a depolarizing block and suggested an alteration in the electrical properties of the muscle membrane A 50-yr-old male with a 30-yr history of progressive muscle dystrophy, exhibited a tonic response to neosugmine in the evoked mechanomyogra M. During recovery from partial neuromuscular block. It is concluded that the type of reaction to neostigmine in patients with neuromuscular disease is unpredictable.

Zufuhr von Polyenfettsauren mit der Nahrung beschleunigt im allgemeinen die Erschopfung der Vitamin E-Reserven des Korpers Foetal-Resorption, verminderte Resistenz gegen oxydative Hamolyse und Lebernekrose bei Ratten sowie Muskel-Dystrophie und exsudative Diathese bei Kuken konnen ohne Nahrungs-Polyenfettsauren entstehen. Peroxydierung und Braunfarbung des Korperfettes (Ceroid-Bildung) und dazu gekoppelte oxydative Destruktion von Vitamin A erfordern stark ungesattigte Fettsauren, z. B. solche, die in Fischtranen vorkommen. Fur die Depigmentierung der Incisiven der Ratte genugt Schweineschmalz. Encephalomalacie bei Kuken ist spezifisch abhangig von Fettsauren der Linolsaure-Reihe. Es wird bestatigt, das Zufuhr von Polyenfettsauren mit der Nahrung durch genugende Zufuhr von Vitamin E begleitet werden mus. Relationship between Vitamin E and Polyunsaturated Fatty Acids The addition of polyunsaturated fatty acids to food generally accelerates the exhaustion of vitamin E reserve of the body. Foetal resorption, decreasing resistance against oxidative haemolysis and liver necrosis in rats as well muscle dystrophy and exsudative diathesis in chickens can arise even without polyunsaturated fatty acids in the food. Peroxidation and brown-colouration of body fat (ceroid-formation) and the accompanying oxidative destruction of vitamin A necessiate high polyunsaturated fatty acids, e. g. such as those occur in fish oils. Encephalomalacy in the chickens is specifically dependent on fatty acids of linoleic acid series. It has been confirmed that the addition of polyunsaturated fatty acids to food must be accompanied with sufficient addition of vitamin E.

SummaryA deficiency in pups produced from dogs maintained for long periods of time on mineralized evaporated milk has been described. The condition is undoubtedly identical with muscle dystrophy previously described in rats, guinea pigs and rabbits and is cured by synthetic α-tocopherol if therapy is initiated before the symptoms are too far advanced.

Succeeding to the previous work, in which the so-called “Sekoke” disease of carp was shown to be a typical muscle dystrophy due to oxidized oil, the preventive effect of antioxidants, methylene blue, BHA and ethyl gallate, was examined and compared with that of DL-α-tocopheryl acetate. In addition, oxidized saury oil of different peroxide values and acetone-soluble lipids from dried silk-worm pupae were tested. As shown in Tables 1 and 4, these antioxidants except DL-α-tocopheryl acetate are ineffective, although they were reported to alleviate some of disorders induced by oxidized fish oils in terrestial animals. It is also observed that the muscle dystrophy is induced by the oxidized saury oil of a very low peroxide value and also by acetone-soluble lipids from dried silk-worm pupae. This may suggest that peroxide has little connection with the incidence of muscle dystrophy. Results of chemical analyses on the test diets and animals are summarized in Tables 2, 3 and 5.

The nutritional muscle dystrophy of guinea pigs and rabbits is primarily a degeneration of the muscle fibers and is not associated with visible alterations of the peripheral nerves or their motor terminals.

– Masseter muscles from normal and dystrophic mice were investigated with the electron microscope and by the use of histochemical techniques for myosin ATPase and succinic dehydrogenase activity. The observations show that the muscle fibers arc severely affected in the masseter of the dystrophic mouse.

The presence of fibrillation in the muscles of the Bar Harbor strain of dystrophic mice has previously been reported from this laboratory.1We have observed that the electromyogram from dystrophic mice of this strain is strikingly similar to that recorded from muscles of patients suffering from dystrophia myotonica. The muscles of such patients and animals are hyperirritable, and the records obtained by the insertion of a concentric needle electrode reveal the presence of short motor volleys of high frequency against a background of electrical activity characteristic of denervated muscle. In order to demonstrate the presence of fibrillation, free of the superimposed activity from innervated structures, it was decided to study the electrical activity of muscles in dystrophic mice and patients in whom the motor nerves were blocked. The identification of characteristics common to both the dystrophy in this strain of mice and a particular form of dystrophy in man

During the past year we have been studying the vitamin E requirement of rabbits for the cure and prevention of nutritional muscle dystrophy. Recently, MacKenzie and McCollum1 reported that the rabbit requires 0.7 to 1.0 mg of α-tocopherol per kg of body weight, but this does not quite agree with our Findings. In our experience, rabbits made dystrophic on the Goetsch-Pappen-heimer diet 13 were cured by the daily oral administration of synthetic dl-α-tocopherol acetate in quantities ranging from 0.18 to 1.0 mg per kg of body weight, with most of the cures resulting from doses of 0.2 to 0.5 mg (as free alcohol).We found that a definite correlation exists between the higher requirements and the total α-tocopherol intake. When animals with an apparently high vitamin E requirement were subjected to a new test on a smaller total tocopherol intake, their requirement dropped to a lower level (values ranging from 0.2 to 0.4 mg per kg). These findings suggest that the higher values, as well as the wider range of var...

In recent years there has been a flood of new publications on the pathology of skeletal muscle. From a state of relative neglect the whole field of muscle disease has been transformed into one in which there is active investigation of all aspects of processes involving this tissue. This new and attractive publication on muscular dystrophy in man and animal is the most recent addition to this literature. The subject matter of the book is divided into 12 chapters, nine of which are devoted to human muscular dystrophy and three to metabolic and inherited diseases of muscle in animals. The clinical, genetic, biochemical, and pathological changes which have been found in human cases of muscle dystrophy are extensively reviewed by recognized authorities in this field. Professor Carl Pearson introduces the subject with a systematic account of the pathology of muscle dystrophy. Shapiro and Dreyfus follow with a thorough and informative