Alcohol Protects the Diaphragm during Dietary Restriction

We recently reported that alcoholic rat diaphragm develops greater contractile force than diaphragm of pair-fed control animals. The present experiment examines whether alcohol or dietary restriction is the more likely cause of this surprising finding. We conditioned 10 rats using a liquid diet containing ethanol as 36% of calories. Ten pair-fed control animals received an equal amount of isocaloric, ethanol-free liquid diet. Ten ad libitum control animals had unrestricted access to lab chow and water. Rats were killed after 30 weeks. Left costal diaphragm strips were studied in vitro at optimal length using direct stimulation at supramaximal voltage. Isometric force was measured and divided by muscle cross-section to compute stress. Maximal tetanic stresses developed by muscle from pair-fed controls were systematically less than alcoholic and ad libitum control values (p less than 0.0001); this did not depend on temperature (25 degrees vs. 37 degrees; p greater than 0.50). Pair-feeding increased twitch half-relaxation times (p less than 0.03) and shifted the tetanic stress-stimulation frequency relationship leftward by 10 Hz (p less than 0.01). Diaphragm of pair-fed rats continued to generate lower stresses during the fatigue caused by repeated contractions (p less than 0.01). We conclude that dietary restriction associated with pair-feeding compromises diaphragm performance in rats. Chronic alcohol consumption prevents or reverses these changes, since diaphragm function of alcoholic and ad libitum control animals was not different.     

Interacting effects of Ca2+ and hypoxia in the induction of sarcolemmal damage in mouse diaphragm in vitro

Experiments have been undertaken to investigate the basis for the selective damage of centrally placed fibres in mouse diaphragms exposed to Ca²⁺ loading in vitro. Incubation under hypoxic conditions (non-aerated saline) for 30 min had no discernible effect on the muscle. Incubation for 120 min led to permeabilisation of the sarcolemma (assayed by penetration of Procion Yellow) in 54% of cells. Sarcolemmal permeabilisation was almost completely restricted to centrally placed cells, as has previously been described for the effects of the Ca²⁺ channel agonist Bay K 8644. Ultrastructural damage to the myofibrils and mitochondrial swelling were also widespread amongst centrally placed cells. Permeabilisation was inhibited when hypoxic incubations were carried out in Ca²⁺-free saline. Incubation in hypoxic Ca²⁺-containing saline for 30 min followed by further incubation in Ca²⁺-free, hypoxic saline, up to a total of 120 min, resulted in permeabilisation similar to that seen in muscles incubated for 120 min in Ca²⁺-containing, hypoxic saline. It is suggested that selective damage to central fibres induced by Ca²⁺ loading resulting from treatment with Bay K 8644 is related to increased oxygen demand.     

Myopathy and elevated serum enzymes in a case of hypoparathyroidism

A relation between hypocalcemia and myopathy could be demonstrated by clinical and laboratory evidence in an 8-year-old girl. Clinical and laboratory results are discussed in respect to the specific problems of pediatric membrane physiology.     

The diagnostic significance of large action potentials in myopathy

Electromyographic and histopathological studies were performed on 112 skeletal muscles in 101 subjects with myopathy. The diagnostic significance of large action potentials (LAPs) in myopathy was studied. LAPs were defined as those action potentials with a duration of over 13 ms and an amplitude of over 3 mV (peak to peak). The following results were obtained: Most muscles with LAPs showed the grouped atrophy of small fibers of neuropathic change in addition to myopathic findings. Even in myopathy most LAPs reflected neuropathic change, except in thyrotoxic myopathy. LAPs were not related to an increase of connective tissue increasing the impedance in volume conduction of the action potentials. LAPs were frequently seen in: progressive muscular dystrophy of limb-girdle type; scapuloperoneal dystrophy; distal myopathy; oculopharyngeal dystrophy; myotonic dystrophy; polymyositis; and thyrotoxic myopathy. Other types of myopathy had few LAPs. There were two types of progressive muscular dystrophy. One had LAPs frequently and the other, rarely. In myotonic dystrophy the muscles with LAPs showed scattered small angular fibers, possibly indicating neurogenic changes. Interstitial myositis had LAPs more frequently than parenchymatous polymyositis. The chronic phase of polymyositis had LAPs more frequently than the acute or subacute phases. In thyrotoxic myopathy the muscles with LAPs rarely showed definite neuropathic change histopathologically. Therefore, LAPs in thyrotoxic myopathy may not indicate denervation.     

A histochemical and electron microscopic study of skeletal and cardiac muscle from a Fabry disease patient and carrier

Histochemical and electron microscopic studies were performed in an attempt to clarify the muscle pathology in an 18-year-old man with Fabry disease, showing proximal limb muscle atrophy, and his 52-year-old mother, who is a Fabry carrier with hypertrophic cardiomyopathy. Despite the relatively mild myopathic changes revealed by histochemistry, electron microscopy demonstrated the widespread accumulation of abundant lamellated bodies in myofibers, associated with increased glycogen granules and autophagic vacuoles. The cardiac muscle of the proband's mother revealed a mosaic pattern of normal-appearing and hypertrophic myofibers containing a number of ring-like, lamellated bodies. Although further studies are necessary to support our findings, skeletal muscle is apparently involved in patients with Fabry disease, and a mosaic pattern of cardiac muscle involvement possibly reflecting Lyonization, may be one of the characteristic findings of a Fabry disease carrier.     

Paramyotonia congenita (Eulenburg)

Summary The case of a 71 years old male patient with paramyotonia congenita is described. There was no occurence of spontaneous paresis at room temperature. Lowering the temperature, a loss of muscle power became perceivable in the mechanogram while, at the beginning there was only a slight depression in amplitude of the evoked action potential. After termination of the cooling paresis became even more pronounced. Electric activity too faded away almost entirely. Repetitive stimulation showed a marked fatigability of the muscle. — The findings seem to indicate a direct influence of low temperature on the contractible substance of the muscle.Dedicated to Prof. Dr. Dr. R. Janzen, Hamburg, on the occasion of his 65th birthday.     

A mitochondrial myopathy with a defective respiratory chain and carnitine deficiency

A boy presented suffering from generalised weakness, exercise intolerance and lactic acidosis. The weakness became evident at 2 years. A cerebral CT-scan showed cerebellar atrophy and central and peripheral atrophy of both hemispheres. With trichrome staining about 20% of the muscle fibres showed large areas containing redstaining granular material. Electron microscopic examination showed that this material consisted of areas of mitochondrial proliferation, most of the mitochondria having abnormal ultrastructural characteristics. Pyruvate dehydrogenase complex and citric acid cycle activities were determined by measuring ¹⁴CO₂ production from various labelled substrates. Diminished oxidation rates were found with the patient's muscle homogenate for all substrates tested, indicating a defect in the respiratory chain. The cytochromes were present in normal quantities. Succinate cytochrome c reductase activity was very decreased. Carnitine concentration was decreased in serum and in muscle as well.     

Dystrophia myotonica and hypothyroidism

Summary Two cases of dystrophia myotonia associated with hypothyroidism are reported. This association is not frequent. In both cases the hypothyroidism precipitated an otherwise mild muscular weakness due to dystrophia myotonia. Treatment with dried thyroid improved the muscular power, while the myotonia remained unchanged. Since dystrophia myotonica and hypothyroidism have many presenting symptoms in common, a complete assessment of the thyroid function in every case of dystrophia myotonica seems worthwhile.

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Zusammenfassung Es wird über 2 Fälle von myotonischer Dystrophie berichtet, die durch das Auftreten einer Hypothyreose kompliziert wurden. Diese Kombination ist selten. Die Hypothyreose führte in beiden Fällen zu einer Zunahme der vorher wenig eindrücklichen Muskelschwäche. Die Behandlung mit Schilddrüsenextrakt führte zu einer Besserung der Muskelkraft, während die myotonischen Erscheinungen unverändert blieben. Da die myotonische Dystrophie und die Hypothyreose viele gemeinsame Symptome haben, ist es ratsam, bei jedem Fall von myotonischer Dystrophie die Schilddrüsenfunktion genau zu prüfen.

     

Recurrent exertional rhabdomyolysis and stunted growth

A boy with recurrent exertional rhabdomyolysis and stunted growth is described. Fetal movements were few and the boy was small for gestational age. He always experienced easy fatigability, and he, noted bouts of pigmenturia associated with episodes of considerable malaise. The change in color of the urine was caused by myoglobin. An electromyogram was myopathic. CPK rose during 60 minutes mild exercise. Prolonged moderate exercise could not be performed. Histopathological examination of muscle biopsy revealed an increase in the number of 11 C fibres (20%). Electronmicroscopy revealed the wavy outline of a number of fibres and hypertrophy of sarcoplasmic reticulum elements. No cause for the stunted growth could be detected.We wish to thank Dr. S. L. H. Notermans and Dr. H. M. Vingerhoets for performing the EMG studies. The authors are greatly indebted to Miss M. de Bruijn for her skilful technical assistance. This study was supported by a grant from the Prinses Beatrix Fonds     

新生儿型肉碱棕榈酰转移酶Ⅱ缺乏症3例尸检及文献复习

目的 探讨新生儿型肉碱棕榈酰转移酶Ⅱ缺乏症的临床及病理特征.方法 分析新生儿型肉碱棕榈酰转移酶Ⅱ缺乏症的临床表现、病理改变及串联质谱（MS-MS）分析检测,并复习相关文献.结果 尸检发现新生儿除肌肉出现大量脂肪滴之外,其他全身各个重要脏器心、肝、脾、肾等均有不同程度的脂肪空泡沉积.串联质谱（MS-MS）分析检测报告均符合肉碱棕榈酰转移酶Ⅱ缺乏症检测指标改变.结论 新生儿型肉碱棕榈酰转移酶Ⅱ缺乏症病情危重,为全身系统性疾病;诊断本疾病需结合临床、病理及实验室等各项检查.