Hand dominance and scoliosis in Duchenne muscular dystrophy

Twenty-three patients with Duchenne muscular dystrophy and scoliosis were studied. In all but one patient the major convexity was to the side of the dominant hand. The unsupported growing spine is easily unbalanced by asymmetrical forces imposed on it. From our observations we believe major use of a single upper extremity will result in scoliosis with the major convexity toward the side of the dominant hand. Management should include counterbalancing the postural abnormality imposed by hand dominance as well as unloading the spine frequently during the patient's waking hours.     

Molecular diagnosis of Duchenne muscular dystrophy in Singapore

TL-transgenic mice expressing the thymus leukemia antigen demonstrate a lack of viral clearance following cutaneous HSV infection of the footpad. In this study, both uninfected and HSV-infected TL-transgenic mice demonstrate increased concentrations of IL-4 as well as decreased concentrations of IFN-gamma which may possibly underlie the impairment of viral clearance. Furthermore, lymphocytes from HSV-infected nontransgenic mice, adoptively transferred into HSV-infected TL-transgenic mice, promoted viral clearance and led to an increase in IFN-gamma production. Transgenic mice which were subcutaneously injected with IFN-gamma in the right footpad were also capable of clearing the viral challenge; however, clearance was restricted solely to the right footpad. These studies support the possibility of perturbations in the immune system of TL-transgenic mice and effectively demonstrate the utility of this model system in the study of HSV clearance, persistence, and potential spontaneous reactivation. Moreover, the TL-transgenic animals may provide a useful model system for additional studies requiring a host system skewed toward a Th2 phenotype.     

Stiffness of knee extensors in Duchenne muscular dystrophy

OBJECTIVE: The characteristics of private psychotherapy patients of medical psychoanalysts are described. METHOD: A structured interview was administered to 51 medical psychoanalysts. Patients' demographic characteristics, historical features, and other clinically relevant aspects of behavior were assessed. RESULTS: Of 575 patients, 88% had at least one axis I disorder and 46% had at least one axis I and one axis II disorder. Treatment duration varied from less than 6 months to more than 6 years. Forty-three percent of the patients were also treated with psychotropic drugs. CONCLUSIONS: The patients in this cohort met the criteria for DSM-IV psychiatric disorders, had lifetime histories of major psychiatric disturbances, and were not the "worried well."     

The incidence of Duchenne muscular dystrophy in the South East of Scotland

In a survey carried out to determine the incidence of Duchenne muscular dystrophy in the South East of Scotland, 47 cases were ascertained among 177,413 live male births for the years 1953 to 1968. The overall incidence is 1 case in 3,775 live male births (26.5 +/- 3.2 X 10(-5)). This incidence figure has been compared with those reported in nine other studies, and any differences appear likely to be due to varying degrees of ascertainment. So far there is no evidence of any decrease in incidence of the disease in S.E. Scotland as a result of genetic counselling and antenatal foetal sexing.     

Intellectual functioning in Duchenne muscular dystrophy: A review.

Duchenne muscular dystrophy has traditionally been thought to be a primary disease of muscle, but recently it has been suggested that it may be secondary to a neuronal defect or to a generalized disorder of protein synthesis and membrane. However, to date there is no proof to support unequivocally any of these theories. A higher incidence of mental retardation and decreased intellectual functioning has been reported in the medical literature of Duchenne muscular dystrophy patients than for normals or other control groups. Recently there has been strong evidence to suggest that verbal ability, as reflected by the WISC Verbal scale IQ, may be more commonly and significantly impaired in Duchenne muscular dystrophy patients than is nonverbal ability, as reflected by the Performance scale IQ. This article presents a comprehensive review of data from the literature on intellectual functioning in Duchenne muscular dystrophy, as well as methodological issues involved in assessment of intelligence in this population. The intent is to provide a basis for future attempts to relate the intellectual deficit in Duchenne muscular dystrophy to neuropsychological and neurobiological parameters of the disease. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential protein oxidation in Duchenne and Becker muscular dystrophy

BACKGROUND: The fifth edition of the TNM classification contains a number of changes concerning head and neck tumors. The division of Stage IV tumors into three subcategories marks a significant expansion of the stage grouping procedure. METHODS: In a retrospective study, the clinical courses of 3247 patients with carcinoma of the oral cavity, the oro- and hypopharynx, the larynx, the salivary glands, and the maxillary sinus were comparatively evaluated according to the fourth and fifth editions of the TNM classification agreed upon by the International Union Against Cancer and the American Joint Committee on Cancer. The particular aim of this study was to test the prognostic relevance of the subdivision of Stage IV, especially for mucosal carcinoma. RESULTS: In classifying the primary tumor, the most extensive changes were noted for supraglottic and salivary gland tumors. On the basis of the fourth edition of the TNM classification, the following recurrence free 5-year survival rates for 3033 cases of mucosal cancer were calculated: Stage I, 91.0%; Stage II, 78.6%; Stage III, 61.4%; Stage IV, 31.0%. The calculations based on the fifth edition yielded the following: Stage I, 91.0%; Stage II, 77.2%; Stage III, 61.2%; Stage IVA, 32.4%; Stage IVB, 25.3%; Stage IVC, 3.6%. CONCLUSIONS: The adequacy of the revised stage classification in establishing a prognostic hierarchy was confirmed. However, a significant prognostic distinction between N2 metastasis (Stage IVA) and N3 metastasis (Stage IVB) could not be found.     

Cardiac involvement in progressive muscular dystrophy of the Duchenne type

Adaptations during phylogenesis or ontogenesis can occur either by maintaining constant or by increasing the informational content of the organism. In the former case the increasing adaptations to external perturbation are achieved by increasing the rate of genome replication; the increased amount of DNA reflects an increase of total but not of law informational content. In the latter case the adaptations are achieved by either istructionist or evolutionary mechanism or a combination of both. Evolutionary adaptations occur during ontogenesis mainly in the brain-mind, immunological and receptor systems and involve a repertoire of receptors that are., clonally distributed, genome-conditioned and amplified by somatic mutation. Specificity and intensity of responses are achieved a posteriori as a result of natural selection of the clones. The major adaptations during phylogenesis are accompanied by increased complexity. They have been attributed to shifts, short in time and space, against the entropic drive and thus occur notwithstanding the entropic drive and the second law of thermodynamics. The alternative view, is that the generation of complexity is due to the second law of thermodynamics in its extended formulation which includes Prigogine's theorem of minimum entropy production. This view requires however that natural selection provides the biological system with structures that bring the reactions within Onsager's range. The hierarchical organization of the natural world thus reflects a stratified thermodynamic stability. As the evolutionary adaptations generate new information they may be assimilated to Maxwell demon type of processes.     

Functional involvement of cerebral cortex in Duchenne muscular dystrophy

Proximal femoral varus and derotation osteotomy is a common procedure performed in the management of developmental dysplasia of the hip. This procedure imposes high shear stress on the femoral epiphysis, depending on the degree of varus obtained. We report two cases of proximal femoral epiphyseal slip after varus derotation osteotomy and discuss the management and outcome. Such epiphyseal slip may or may not be symptomatic, and a careful radiologic examination should be carried out in suspected cases. Management should be individualised. Surgical correction of varus may be required.     

Cardiac and respiratory involvement in advanced stage Duchenne muscular dystrophy

This study aimed to describe myocardial involvement, respiratory impairment and pulmonary blood flow abnormalities in advanced-stage Duchenne muscular dystrophy (DMD). Twenty-one wheelchair-bound patients, aged from 10 to 24 yr, underwent electrocardiographic and echocardiographic examination, conventional spirometry, diurnal arterial blood gas analysis, and nocturnal polysomnography (SaO2 monitoring). Diagnosis was confirmed by neurological examination, dystrophin analysis at protein and DNA level. Patients were classified into two groups: group A normoxemic (14 cases) and group B with nocturnal hypoxemia (seven cases). Group A was further split into two subgroups, one without, and one with, left ventricular dilation (A1 = nine patients, end diastolic volume (EDV) = 51 ml m-2, ejection fraction (EF) = 56 per cent; A2 = five patients, EDV = 112 ml m-2, EF = 32 per cent; P < 0.05). Left ventricular regional wall motion abnormalities were found in 55, 40, and 43 per cent of groups A1, A2, and B patients respectively. Analysis of pulsed Doppler pulmonary data highlighted a significant reduction in corrected time to peak velocity in group B patients, when compared with control, A1, and A2 groups respectively. In group A, we observed a direct correlation between ejection fraction and corrected time-to-peak velocity. Two patterns of cardiac involvement may be recognized in advanced-stage DMD: left ventricular wall motion abnormalities and dilated cardiomyopathy. Doppler data which could suggest pulmonary hypertension may be observed in patients with dilated cardiomyopathy, and in patients with nocturnal hypoxemia. Therefore, in the management of advanced-stage DMD, a careful diagnosis of the heart-lung relationship should be performed, and both conventional treatment of heart failure and ventilatory therapy are necessary to improve the quality of life and survival in these patients.     

Adenyl cyclase abnormality in Duchenne muscular dystrophy: muscle cells in culture

Cultured muscle cells from patients with Duchenne muscular dystrophy differed from cells of normal individuals and of patients with other muscle diseases. In Duchenne cells, basal activity of adenyl cyclase of myotubes was higher and was not stimulated significantly by epinephrine or isoproterenol, as it was in fused control cells, and the response to fluoride was less. The genetic defect in this disease may be an abnormality of the sruface membrane of muscle.     

Cardiac dysfunction in female gene carriers of Duchenne muscular dystrophy

Cardiac dysfunction and its correlation with skeletal muscle dysfunction were examined in 16 definite female gene carriers of Duchenne muscular dystrophy (DMD). Five out of 16 carriers (31.3%) had cardiac symptoms and 8 carriers (50.0%) showed an increased cardio-thoracic ratio on chest X-ray. Electrocardiographic abnormalities including a high R:S ratio (> or = 1.0) in the V1 lead, deep Q wave (> 3 mm) in the I, II, aVL, V5, and V6 leads, complete right bundle branch block and premature ventricular beats, were observed in 9 carriers (56.3%). On echocardiographic examination, an increase in the end-diastolic dimension of the left ventricle and a decrease in the ejection fraction suggestive of dilated cardiomyopathy were found in 12 carriers (75.0%). Tl-201 myocardial SPECT scan was performed in 2 symptomatic carriers and showed an area of hypoperfusion in the inferio-posterior wall. These findings were similar to previously reported findings in DMD patients. A biopsy of the myocardium was obtained in one carrier with her informed consent for the biopsy. Immunohistochemical staining demonstrated that 75.4% of the myocardial fibers were negative for dystrophin, suggesting that her cardiac dysfunction is caused by the abnormal expression of dystrophin in the cardiac muscle. On examination of the skeletal muscle function, none of the carriers had clinical evidence of muscle weakness or atrophy. However serum creatine kinase activity was elevated in 14 of 16 carriers (87.5%). Computed tomography (CT) of the lower limb muscles demonstrated widened spaces among muscles and moss-eaten appearance of low density areas within muscles and CT value was decreased, suggesting the subclinical involvement of the skeletal muscle. In the carriers without cardiac symptoms, there was a negative correlation (p < 0.05) between the end-diastolic dimension of the left ventricle and the CT value of the biceps femoris muscle (a muscle with the lowest CT value among the lower limb muscles). This indicates that there was an apparent correlation between the cardiac and skeletal muscle dysfunction. These findings suggest a high frequency of clinical and subclinical involvement of the cardiac and skeletal muscles in DMD carriers. To protect them from cardiac failure, cardiac dysfunction in DMD carriers needs to be examined closely and treated appropriately before the carriers become symptomatic.     

Sensorineural hearing loss in the mdx mouse: a model of Duchenne muscular dystrophy

Sensorineural hearing loss has been identified in several types of muscular dystrophy, but few studies have investigated any relationship between Duchenne muscular dystrophy and hearing. An animal model of Duchenne muscular dystrophy, the mdx mouse, exhibits the same genetic defect as humans. We performed brainstem auditory evoked responses on mdx and control mice in order to assess sensorineural hearing loss. The amplitude and latency of wave I for each animal were measured at increasing sound pressure levels. A significant increase in threshold and a decrease in wave I amplitude were found in the mdx mice. These results indicate that significant sensorineural hearing loss is associated with muscular dystrophy in the mdx mouse. Possible cellular mechanisms contributing to the hearing deficit are presented.     

Degeneration and regeneration of striated skeletal muscle fibers in Duchenne muscular dystrophy

Like all other muscular dystrophies, Duchenne muscular dystrophy is characterized by the coexistence of degenerative lesions of the muscle fibers and of regenerative changes. The present study has been carried out in order to precise the degree of regeneration at different stages of the disease, by analyzing the expression of several markers of cell proliferation and of muscular differentiation. In the two affected foetuses of our series, the m. quadriceps is histologically normal, except for the absent expression of immunoreactive dystrophin. The quadriceps from the eight children of our series (20 months-16 years) all present clear dystrophic changes. Muscle regeneration is characterized by activation of the satellite cells, by their multiplication followed by their fusion giving birth to regenerative fibers. By studying the expression of muscular markers (vimentin, desmin, isoforms of the myosin heavy chains), it has been possible to define more precisely the degree of maturation and of differentiation of these regenerative fibers. Our results suggest that an abortive regeneration of the muscle fibers in Duchenne muscular dystrophy can explain, at least partly, the progressive evolution of this disease.     

The clinical and molecular genetic approach to Duchenne and Becker muscular dystrophy: an updated protocol

Detection of large rearrangements in the dystrophin gene in Duchenne and Becker muscular dystrophy is possible in about 65-70% of patients by Southern blotting or multiplex PCR. Subsequently, carrier detection is possible by assessing the intensity of relevant bands, but preferably by a non-quantitative test method. Detection of microlesions in Duchenne and Becker muscular dystrophy is currently under way. Single strand conformational analysis, heteroduplex analysis, and the protein truncation test are mostly used for this purpose. In this paper we review the available methods for detection of large and small mutations in patients and in carriers and propose a systematic approach for genetic analysis and genetic counselling of DMD and BMD families, including prenatal and preimplantation diagnosis.     

Cardiomyopathy may be the only clinical manifestation in female carriers of Duchenne muscular dystrophy

Cardiomyopathy was reported in a few Duchenne muscular dystrophy (DMD) carriers with clinical evidence of myopathy. We report two carriers with dilated cardiomyopathy, increased serum CK, and no symptoms of muscle weakness. In heart biopsies of both patients, dystrophin-the protein product of DMD locus--was absent in many fibers. Dilated cardiomyopathy may be the only manifestation of dystrophin gene mutation in carriers.     

Muscular uptake of Tc-99m MIBI and TI-201 in Duchenne muscular dystrophy

Lack of dystrophin, a protein localized to the inner surface of the sarcolemma of the muscle fiber, is the cause of Duchenne type muscular dystrophy. Plasma membrane damage of the muscular fiber occurs, followed by Ca++ influx into the fibers. There is severe mitochondrial damage in dystrophic but still viable fibers. Five children aged 5-7 years were studied with MRI, TI-201, and Tc-99m sestamibi scintigraphy of the thighs. These three methods showed that the sartorius is the least damaged muscle in Duchenne type muscular dystrophy. MRI showed mild damage of adductors and quadriceps; TI-201 scintigraphy showed a marked reduction of radioactivity in the same muscles; Tc-99m sestamibi uptake occurred only in the sartorius muscle; the quadriceps was not imaged and adductors showed a faint image. A decrease of water in muscular fibers as well as fatty fibrous substitution, occurs after death of the fibers, whereas plasma membrane and mitochondrial damage reduced the uptake of tracers when the fiber is still viable. The interesting mismatch between sestamibi and TI-201 can be explained by considering that the cellular mechanism of uptake and retention of Tc-99m sestamibi involves both plasma membrane and mitochondria, whereas the uptake of TI-201 is only affected by plasma membrane damage.