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Factors controlling muscle protein synthesis and degradation.

Insulin is a well-known anabolic hormone. The mechanism of insulin's protein anabolic effect remains controversial. Although insulin undoubtedly inhibits protein degradation, its effect on protein synthesis is incompletely defined. Recent studies reviewed in this article highlight the methodologic limitations in studying the effect of insulin on protein synthesis. These methodological issues are related to the hypoaminoacidemia that ensues after insulin administration and to the difficulty in measuring the obligatory precursor pool (aminoacyl tRNA) label. Differential responses to unweighing in different muscle proteins has been demonstrated. The protein loss during unweighing is due to the loss of myofibrillar proteins, although sarcoplasmic proteins are spared. A recent study has found that lipid emulsion has no effect on whole protein degradation but decreases forearm protein degradation and synthesis. Age-related muscle wasting in humans has been shown to be related to a decline in fractional myofibrillar protein synthesis rate. Although some progress has been made by recent studies, refined methodologies are needed to define the regulation of muscle protein turnover in humans.

Adult↗

Late effects of poliomyelitis.

Muscular atrophy and decreased functional abilities are recognized as late complications of poliomyelitis. This study sought to more clearly define late-onset, postpolio muscular weakness--age of onset, symptoms, and severity--and to determine whether people might benefit from environmental modification, respiratory aids, and orthoses. A total of 183 postpolio patients were examined by a physician and completed a questionnaire on their ambulatory status and related musculoskeletal and respiratory symptoms. Of those participating in the study, 154 claimed to be experiencing late deterioration in strength. The syndrome included decreased endurance, more limited ambulation, and increased weakness in the previously affected limb/s. For those describing late-onset weakness, average ages were determined for the onset of polio (8.3 years), the onset of postpolio muscular weakness (42.3 years), and the latent period of stable functioning (34.8 years). Patients claimed to have experienced a new, lower level of strength for an average of 4.7 years. All 33 patients who had undergone muscle transfer surgery were experiencing late-onset weakness in that extremity. Fasciculations (51%) and long-bone fractures secondary to falls (21%) were common sleep disturbances occurred frequently (31%) even in those without prior bulbar involvement. Upper motor neuron signs were present in only one case. Bracing was rare (16%) and the braces used were usually old. The subjects did not report a steadily or rapidly progressive decline, but rather described a steplike decrement with long plateaus. The population described losses in strength that had significant bearing on functional status and general health.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

CAG repeat expansion in autosomal dominant pure spastic paraplegia linked to chromosome 2p21-p24.

CAG repeat expansions have been identified as the disease-causing dynamic mutations in the coding regions of genes in several dominantly inherited neurodegenerative disorders, including spinobulbar muscular atrophy, Huntington's disease, dentatorubral-pallidoluysian atrophy, spinocerebellar ataxia type 1, 2 and 6 and Machado-Joseph disease. The CAG repeat expansions are translated to elongated polyglutamine tracts and an increased size of the polyglutamine tract correlates with anticipation, the cardinal feature, seen in all these diseases. Autosomal dominant pure spastic peraplegia (ADPSP) is a degenerative disorder of the central motor system clinically characterized by slowly progressive and unremitting spasticity of the legs, hyperreflexia and Babinski's sign. Like the established CAG repeat diseases ADPSP is characterized by both inter- and intrafamilial variation and anticipation. Using the Repeat Expansion Detection (RED) method, we have analyzed 21 affected individuals from six Danish families with the disease linked to chromosome 2p21-p24. We found that 20 of 21 affected individuals showed CAG repeat expansions versus two of 21 healthy spouses, demonstrating a strongly statistically significant association between the occurrence of the repeat expansion and the disease (Fisher's test, P < 10(-5)) suggesting that a CAG repeat expansion is involved presumably as a dynamic mutation in ADPSP linked to chromosome 2p21-p24. The size of the expansion is estimated to be > or = 60 CAG repeat copies in the affected individuals. The CAG repeat expansion is very likely translated and expressed as indicated by the detection of a polyglutamine-containing protein in an ADPSP patient.

Chromosomes, Human, Pair 2↗

Muscle fiber conduction velocity in situ (MFCV) in denervation, reinnervation and disuse atrophy.

OBJECTIVES: Muscle fiber conduction velocity (MFCV) was performed in disuse atrophy, in denervated muscle and during reinnervation as a possible index of muscle atrophy, and to clarify the evolution of the fiber size. MATERIAL AND METHODS: MFCV was performed in 12 patients with complete denervation of biceps brachii muscle and during various stages of reinnervation. Twenty-one patients with disuse quadriceps atrophy were also tested. Invasive MFCV was performed according to the method reported elsewhere (2). RESULTS: MFCV decreased significantly in denervated muscles. Reduction of MFCV was found during the first weeks and was progressive. Peak frequency in histograms decreased and the normal Gaussian distribution was lost. MFCV increased progressively after reinnervation with coexistence of slow and significant increase of faster MFCV. MFCV decreased significantly also during the first weeks after immobilization and improved by rehabilitation therapy. CONCLUSION: MFCV is a reliable method to test the muscle fiber size after denervation and immobilization, and its evolution by reinnervation and therapy.

Adolescent↗

New neuromuscular symptoms in patients with old poliomyelitis: a three-year follow-up study.

Fourteen survivors of paralytic poliomyelitis experienced new symptoms after years of stability. Seven patients had lost functional capacity, with joint pain, instability and recurrent falls, but were again stable and remained essentially unchanged during a 3-year follow-up period. Seven others had late postpoliomyelitis muscular atrophy (PPMA) with new weakness, wasting, fasciculations and myalgia in muscles originally spared or seemingly recovered. Muscle biopsy from newly affected muscles showed new and chronic denervation with interstitial inflammation in 3 patients. Antibody titers to poliomyelitis virus were not elevated in the CSF, but oligoclonal IgG bands were found in 3 PPMA patients. During the 3-year follow-up period, PPMA patients showed signs of slow progression which continued to be focal. It is concluded that the new symptoms in postpolio patients may be musculoskeletal and relatively stable, or due to a slowly progressive, focal, and apparent benign new motor neuron deterioration.

Adult↗

[Non hypertrophic amyloid myopathy with muscular inflammation in plasma cell dyscrasia].

The case of a 41 year old woman with amyloid myopathy is reported. Clinical involvement consisted of limb girdle muscle weakness, mild scapular muscle atrophy and dysphagia. In contrast with the published cases, abnormal firmness, pseudohypertrophy of the musculature and macroglossia were absent. Muscle biopsy showed endo- and perimysial amyloid deposits but also inflammatory infiltrates. Inflammatory cells typing was studied by immunocytochemical methods and revealed a predominant T-helper cell infiltration. Free kappa light chains were present in serum and urine. Serum immunoglobulin levels were reduced. Bone marrow examination revealed mild plasmocytosis without abnormal cells. Immunofluorescence and immunoperoxidase techniques for identification of the type of amyloid fibrils showed positivity with antisera to kappa light chains. A 4-year follow-up revealed a progressive worsening of muscle weakness despite immunosuppressive treatment. No malignant plasmocytosis occurred. The unusual inflammatory muscle infiltration observed in this case may suggest an associated polymyositis.

Adult↗

Natural history of denervation in SMA: relation to age, SMN2 copy number, and function.

Denervation was assessed in 89 spinal muscular atrophy (SMA) 1, 2, and 3 subjects via motor unit number estimation (MUNE) and maximum compound motor action potential amplitude (CMAP) studies, and results correlated with SMN2 copy, age, and function. MUNE and maximum CMAP values were distinct among SMA subtypes (p < 0.05). Changes in MUNE and maximum CMAP values over time were dependent on age, SMA type, and SMN2 copy number. SMN2 copy number less than 3 correlated with lower MUNE and maximum CMAP values (p < 0.0001) and worse functional outcomes. As SMN2 copy number increases, so does functional status (p < 0.0001). Change in MUNE longitudinally over the time intervals examined in this study was not statistically significant for any SMA cohort. However, a decline in maximum CMAP over time was apparent in SMA2 subjects (p = 0.049). Age-dependent decline in MUNE and maximum CMAP was apparent in both SMA 1 (p < 0.0001) and SMA 2 (p < 0.0001) subjects, with age as an independent factor regardless of type. Maximum CMAP at the time of the initial assessment was most predictive of functional outcome (p < 0.0001). Prospective longitudinal studies in four prenatally diagnosed infants demonstrated significant progressive denervation in association with symptomatic onset or functional decline. These data highlight the potential value of such measures in increasing our understanding of pathophysiological factors involved in denervation in SMA.

Activities of Daily Living↗

Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina.

Gyrate atrophy of the choroid and retina is a disease characterized by progressive constriction of visual fields, a 10-fold to 20-fold elevation in plasma ornithine, and depressed activity of L-ornithine:2 oxoacid aminotransferase. Morphologically conspicuous but clinically unimportant atrophy of Type II muscle fibers progresses concomitantly with the eye disease. A pathogenic component of the disease may be deficient formation of creatine, caused by hyperornithinemia, which leads to a shortage of cellular phosphocreatine energy stores. To test the therapeutic value of replenishing the postulated deficiency of creatine, we supplemented the diet of seven patients with 1.5 g of creatine daily. During one year of this treatment the diameters of Type II muscle fibers increased from 34.1 +/- 7.1 to 49.9 +/- 7.0 micron (mean +/- S.D.) (P less than 0.001). There was no significant increase in the diameters of Type I fibers. The visual-field tests showed no further constriction during the therapy. Fundus photography revealed slow impairment at an age otherwise associated with rapid progression of the disease. These promising preliminary results need further evaluation with long-term follow-up studies.

Administration, Oral↗

[Progressive atrophy of the globus pallidus--case report].

The authors report a case of atrophy of the globus pallidus in a woman aged 25 years, diagnosed alive. The diagnosis was based to a large extent on MRI findings. Atrophy of the globus pallidus (AGP) is a rare disease, recognized mostly in neuropathological examination. Its etiopathogenesis has not been explained so far. Since no specific abnormalities have been detected in laboratory tests, the clinical diagnosis of AGP is only probable. However, AGP should be suspected if such extrapyramidal symptoms are present as dystonia, choreoathetosis, muscular rigidity, and characteristic localisation of lesions in MRI. At present only comprehensive symptomatic treatment is possible.

Adult↗

Diaphragm atrophy and weakness in cortisone-treated rats.

Despite frequent therapeutic use, the potential of corticosteroids to produce respiratory muscle myopathy is unknown. We studied effects of chronic steroid treatment on diaphragm mass and function. Eleven Sprague-Dawley rats were treated with cortisone acetate (100 mg.kg-1.day-1 im) for 10 days. Controls (injected with vehicle) included 11 freely eating rats and 11 animals pair fed to match food intake of cortisone rats. Steroid treatment depressed body weight 30% compared with controls. Mass of diaphragm, gastrocnemius, and extensor digitorum longus showed significant atrophy (30%); heart and soleus were unaffected. Isometric contractile properties of costal diaphragm strips were studied in vitro using direct stimulation. The force-frequency relationship was markedly depressed by steroid treatment, both at low and high frequencies. However, force developed per unit cross-sectional area was similar among all three groups, as were twitch characteristics. When stimulated every minute, forces developed by control strips fell progressively, whereas the forces of cortisone-treated strips remained unchanged. When stimulated every 5 s, the fall in force was not different between groups. We conclude that cortisone weakened the diaphragm by decreasing muscle mass but made the diaphragm more resistant to one form of fatigue in vitro.

Animals↗

Active muscle length reduction progressively damages soleus in hindlimb-suspended rabbits.

This study describes the morphologic changes in rabbit soleus muscle following hindlimb suspension (HS) for 1 to 4 weeks (group A); or following HS with hindfeet passively dorsiflexed, by means of an elastic band, for 1 to 2 weeks (group B). In the latter, elastic band use allowed phasic contractions of foot extensor muscles against resistance and prevented 35% chronic soleus shortening, which occurred in group A animals. In group A, the soleus revealed progressive muscle atrophy and myofibrillar damage. Myofibrils underwent dissolution, muscle regeneration was ineffective, and adipose tissue developed from about 2-week suspension onward. Conversely, passive dorsiflexion of unloaded hindfeet was essential in maintaining mass and structural muscle integrity in the soleus of group B. It is hereby demonstrated that HS-induced soleus damage in the rabbit is progressive, and can be prevented, avoiding long-term shortening of soleus and its phasic unloaded contractions. Soleus sensitivity to unloading conditions, such as HS, tenotomy, and hypogravity, may depend on the particular physiology of this tonic antigravity muscle, engaged mainly in developing long-lasting isometric contractions in a stretched length.

Animals↗

Anterior submuscular transposition of the ulnar nerves by the Learmonth technique.

Thirty-eight patients with progressive posttraumatic ulnar neuropathy at the elbow underwent anterior submuscular transposition of their nerves. Multiple mechanical causes of neuropathy were identified. Fourteen patients had undergone previous surgery for ulnar neuropathy, while 24 had not. Postsurgical follow-up averaged 23.1 months. The operative technique is described and illustrated in detail. Complications attributable to surgery were minimal. No absolute prognostic factors could be identified, and even those patients with significant muscular atrophy or time delay before operation were generally benefited. If prior surgery had induced significant scarring and neural damage, the prognosis for recovery was considerably worse, as it also was for patients who had severe preoperative dysesthesia or pain. Four patients thought to represent examples of double crush or compression syndrome were identified.

Adolescent↗

[Gyrate atrophy of the choroid and retina: a case report].

BACKGROUND: Gyrate atrophy of the retina and choroid is a rare disease, with recessive autosomal transmission, characterized by progressive chorioretinal atrophy causing blindness. It results from a congenital deficit in aminotransferase ornithine. CASE REPORT: The authors present the case of a young patient aged 15 years old consulting for a progressive fall of visual acuity with hemeralopia. Eye funduscopy showed regions of confluent rounded chorioretinal atrophy. The visual field, the electroretinogram and the retinal angiography were all alterated. Gyrate atrophy of the retina and choroid was evocated. DISCUSSION: It is a systemic and rare metabolic disease where ocular features are dominating. Differencial diagnosis are pigmentary retinopathies. Cataract and/or myopia are often joined to the retinal lesions. General signs could consist in muscular weakness, thin and rare hairs and mental retardation. More than; visual fields, electroretinogram, retinal angiography that are alterated; the plasmatic dosage of the ornithine is often high. The treatment is based on the dietetics with uncertain results. The genic therapy would be the treatment of future.

Adolescent↗

Madras pattern of motor neuron disease in South India.

This paper presents the clinical features in 12 patients with the Madras pattern of motor neuron disease (MMND) seen over a period of 10 years. Ten of the patients were from other parts of South India, outside Madras. Young age at onset, sporadic occurrence, sensorineural deafness, bulbar palsy, diffuse atrophy with weakness of limbs and progressive but benign course were the striking features. Electromyography revealed chronic partial denervation. MMND formed 3.7% of all forms of motor neuron disease. Although isolated cases have been seen elsewhere in India, this is the first report of a large number of patients of MMND seen outside Madras (Tamil Nadu). Recognition of this clinical syndrome is of importance for prognostication and as well for search of possible aetiological factors.

Adolescent↗

The effect of hydrocortisone on the serum creatine kinase activity of muscles diseases.

Intravenous administration of a single dose of hydrocortisone to patients with the Duchenne type of progressive muscular dystrophy, carriers of Duchenne dystrophy gene caused a short-lasting rise of the serum creatine kinase activity. Administration of hydrocortisone also raised the serum CPK activity in some carriers with a primarly normal CPK level. This phenomenon was observed, though to a lower degree, in limb-girdle muscular dystrophy. The serum CPK activity was sometimes increased after hydrocortisone administration in patients with polymyositis and Kugelberg-Welander spinal muscular atrophy. This phenomenon was never observed in the control group or in cases of myotonic dystrophy. The mechanism of this effect of hydrocortisone on the CPK level is still unknown.

Adult↗

An unusual degenerative disorder of neurons associated with a novel intranuclear hyaline inclusion (neuronal intranuclear hyaline inclusion disease). A clinicopathological study of a case.

A 21-year-old woman with an unusual, progressive, degenerative neurological disorder is described. The disorder is characterized clinically by behavioral abnormality, peculiar involuntary movements, and ataxia starting in early childhood and subsequent development of dementia, choreoathetosis, rectal and bladder incontinence, bulbar and spinal muscular weakness, pes cavus, kyphoscoliosis, and generalized seizures. The clinical manifestations are correlated, with widespread pathological changes affecting almost all neuronal systems. The pathological changes are discussed in relation to the wide spectrum of "multisystem atrophies." Particular attention is directed to the ubiquitous occurrence of a novel intranuclear, eosinophilic, hyaline inclusion in almost all types of central, peripheral, and autonomic neurons. The ubiquitous neuronal involvement seems to explain the diffuse multiple system degeneration. The pathogenesis of the neuronal inclusions is unknown, but it is speculated that the disorder may represent a metabolic abnormality affecting the nuclear protein of neurons, rather than a viral infection. The pathological features, consisting of the neuronal intranuclear hyaline inclusions associated with multiple system atrophy, have not hitherto been described, and "neuronal intranuclear hyaline inclusion disease" is proposed as a name for the disorder. Rectal biopsy demonstrating the intranuclear hyaline inclusions in ganglion cells of the hyenteric plexuses may serve as a diagnostic procedure for the disorder.

Adult↗

[An autopsy case of complicated form of spastic paraplegia with amyotrophy, mental deficiency, sensory impairment, and parkinsonism].

An autopsied case of complicated form of spastic paraplegia with many unusual clinical and pathological features is reported. Present case: a 31-year-old male. His parents are first cousins. Pregnancy and delivery had been unremarkable. Though he was mentally retarded, his physical development was normal. He was considered normal until age 10. He suffered from progressive disturbance in gait at the age of 11. He could not walk without assistance at the age of 22. Neurological examination revealed the following findings. He was obese and mentally deteriorated. Spastic paraplegia with increased tendon reflexes and pathological reflexes was prominent. Though slight sensory disturbance was present in the lower extremities, neither involuntary movement nor cerebellar ataxia was observed. In the age of late 20's, dementia, general muscular atrophy, and Parkinsonism developed. At the age of 30, he could not move by himself. He was apathic and indifferent, and showed forced laughing. Muscle tonus was flaccid because of general muscular atrophy and peripheral neuropathy. He died of acute gastric enlargement. Neuropathological findings were characterized by mal-development of the central nervous system (CNS) and the multisystem degeneration. There existed cerebral white matter hypoplasia with hypogenesis of the corpus callosum and ectopia of neurons of the cerebral and cerebellar cortex. Hypoplasia of melanin pigment was also observed in the remaining neurons of the substantia nigra and the locus ceruleus. Many neurons in the CNS included lipofuscin granules of variable shapes. Some of them showed clusters of several block-like inclusions which were green with luxol fast blue and cresyl violet stain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long-term results of triple arthrodesis in Charcot-Marie-Tooth disease.

We evaluated sixteen patients who had Charcot-Marie-Tooth disease and had had a total of thirty triple arthrodeses. The average age at the time of operation was fifteen years, and the average length of follow-up was twenty-one years. Of the thirty feet, the result in two (7 per cent) was rated excellent; in five (17 per cent), good; in nine (30 per cent), fair; and in fourteen (47 per cent), poor. Each of the fourteen feet that had a poor result had severe impairment of function and needed an orthosis. Six limbs had an arthrodesis of the ankle for degenerative joint disease. Progressive muscle imbalance resulted in recurrent cavovarus deformity in seven feet that initially had had satisfactory alignment. Degenerative changes of the ankle and joints of the mid-part of the foot were noted radiographically in twenty-three feet. The large number of unsatisfactory long-term results in these patients who had had a triple arthrodesis for deformity of the foot secondary to progressive peripheral neuropathy differs from those in earlier reports on patients who had poliomyelitis, who retained normal sensation and had a permanent, stable muscle imbalance. We believe that triple arthrodesis should be considered only as a salvage procedure in patients who have progressive peripheral neuropathy and should be limited to those who have severe, rigid deformity.

Adolescent↗