Humans ; Muscular Dystrophy, Duchenne ; physiopathology ; therapy ; Respiratory Physiological Phenomena

OBJECTIVETo investigate the clinical and lab features of sibling brother and sister both with Duchenne muscular dystrophy (DMD).

METHODSWe conducted comprehensive clinical and lab investigations including the test of serum enzymes, electromyography (EMG), electrocardiography, color Doppler echocardiography, HE staining of skeletal muscles, immunohistochemical study of dystrophin and utrophin, multiple ligation probe amplification (MLPA) on exon 1-79 of dystrophin gene, and short tandem repeat-poly- merase chain reaction of CA repeats located in dystrophin gene.

RESULTSThese two patients were confirmed to suffer from DMD. They were characterized by typical features of DMD including typical clinical manifestations, increased serum enzymes, EMG presenting myogenic impairment, HE staining presentation belonging to DMD, negative dystrophin in brother, and inconstantly positive on the sarcolemma of sister. Furthermore, no deletion or duplication was found in the 1-79 exons of dystrophin gene. The suffering brother and sister carried the same maternal X chromosome.

CONCLUSIONSCarriers of DMD gene show typical clinical and laboratory manifestations of DMD. Comprehensive examinations should be performed for such carriers.

Dystrophin ; genetics ; Female ; Genetic Linkage ; Heterozygote ; Humans ; Male ; Muscular Dystrophy, Duchenne ; genetics ; metabolism ; physiopathology ; Siblings

Duchenne muscular dystrophy (DMD) is a dystrophinopathy, and its associated gene is located on Xp21. Moreover, utrophin, a recently identified structural homologue of dystrophin is reported to be up-regulated in DMD. In order to investigate the association between utrophin and muscle regeneration in DMD, an immunohistochemical study using antibodies to utrophin, dystrophin, vimentin and desmin was carried out in 17 cases of DMD, 3 cases of polymyositis and 1 case of dermatomyositis. Dystrophin was negative in almost all cases of DMD, but positive in all cases of inflammatory myopathy (IM). Utrophin was positive in 94.0% of DMD and in 75.0% of IM. 36.4% of the myofibers were positive in DMD, as compared to 10.5% in IM (p=0.001). In both groups, utrophin positivity was present most commonly in small regenerating fibers (p=0.001, 0.013). Vimentin and desmin were intensely positive in regenerating fibers in all cases of DMD and IM. 34.4% and 35.4% of myofibers were positive for vimentin and desmin in DMD, as compared to 21.8% and 20.9% in IM (p=0.001, 0.001). In both groups, vimentin and desmin positivity were present most commonly in small regenerating fibers (p=0.001, 0.001). The staining intensities of utrophin, vimentin and desmin were also higher in small regenerating fibers. These results show that utrophin up-regulation is regeneration-associated, and that it is proportional to the quantity of regenerating myofibers, but is not specific for DMD.
Adolescent ; Adult ; Child ; Child, Preschool ; Cytoskeletal Proteins/*metabolism ; Female ; Human ; Infant ; Male ; Membrane Proteins/*metabolism ; Middle Aged ; Muscle Fibers/*physiology ; Muscle, Skeletal/*physiopathology ; Muscular Dystrophy, Duchenne/*physiopathology ; *Regeneration

The aim of this study was to investigate the factors affecting cough ability, and to compare the assisted cough methods in patients with Duchenne muscular dystrophy (DMD). A total seventy-one male patients with DMD were included in the study. The vital capacity (VC) and maximum insufflation capacity (MIC) were measured. The unassisted peak cough flow (UPCF) and three different techniques of assisted peak cough flow were evaluated. UPCF measurements were possible for all 71 subjects. But when performing the three different assisted cough techniques, peak cough flows (PCFs) could be obtained from only 51 subjects. The mean value of MICs (1801+/-780cc) was higher than that of VCs (1502+/-765cc) (p< 0.01). All three assisted cough methods showed a significantly higher value than the unassisted method (F=80.92, p< 0.01). The manual assisted PCF under MIC (MPCFmic) significantly exceeded those produced by manual assisted PCF (MPCF) or PCF under MIC (PCFmic). The positive correlation between the MIC, VC difference (MIC-VC), and the difference between PCFmic and UPCF (PCFmic-UPCF) was seen (r= 0.572, p< 0.01). The preservation of pulmonary compliance is important for the development of an effective cough as well as assisting the compression and expulsive phases. Thus, the clinical importance of the inspiratory phase and pulmonary compliance in assisting a cough should be emphasized.
Adolescent ; Child ; Cough/*physiopathology ; Humans ; Inspiratory Capacity ; *Lung Compliance ; Male ; Muscular Dystrophy, Duchenne/*physiopathology/*therapy ; Pulmonary Ventilation ; *Respiratory Therapy ; Vital Capacity

PURPOSE: The purpose of this study is to investigate how respiratory muscle strength correlates to cough capacity in patients with respiratory muscle weakness. MATERIALS AND METHODS: Forty-five patients with amyotrophic lateral sclerosis (ALS), 43 with cervical spinal cord injury (SCI), and 42 with Duchenne muscular dystrophy (DMD) were recruited. Pulmonary function tests including forced vital capacity (FVC) and respiratory muscle strength (maximal expiratory pressure, MEP; maximal inspiratory pressure, MIP) were performed. The correlation between respiratory muscle strength and cough capacity was analyzed. RESULTS: In the SCI group, FVC in a supine position (2,597 +/- 648 mL) was significantly higher than FVC in a sitting position (2,304 +/- 564 mL, p < 0.01). Conversely, in the ALS group, FVC sitting (1,370 +/- 604 mL) was significantly higher than in supine (1,168 +/- 599 mL, p < 0.01). In the DMD group, there was no statistically significant difference between FVC while sitting (1,342 +/- 506 mL) and FVC while supine (1,304 +/- 500 mL). In addition, the MEP and MIP of all three groups showed a significant correlation with peak cough flow (PCF) (p < 0.01, Pearson's correlation analysis). In the SCI group, MIP was more closely correlated with PCF, while in the ALS and DMD groups, MEP was more closely correlated with PCF (p < 0.01, multiple regression analysis). CONCLUSION: To generate cough flow, inspiratory muscle strength is significantly more important for SCI patients, while expiratory muscle function is significantly more important for ALS and DMD patients.
Adult ; Amyotrophic Lateral Sclerosis/*physiopathology ; Cough/*physiopathology ; Female ; Humans ; Inspiratory Capacity ; Male ; Middle Aged ; Muscle Strength/*physiology ; Muscle Weakness/pathology/*physiopathology ; Muscular Dystrophy, Duchenne/*physiopathology ; Respiratory Muscles/pathology/*physiopathology ; Spinal Cord Injuries/*physiopathology

OBJECTIVEStudy the improvement of locomotive faculty of dystrophin/utropin gene double knock-out mice (dko mice) by transplanting bone marrow stem cells.

METHODSThe bone marrow stem cells of C57BL/6 mice (4- to 5-weeks age) were cultured in vitro for three days, before transplanted intravenously (1.0 x 10(7) for each) into 11 dko mice (7- to 8-weeks age). The dko mice were irridiated with 7Gy gamma-ray before transplantation. 8-9 weeks after transplantation, the locomotroy function, electromyography items and expression of dystrophin in transplanted mice and controls were observed.

RESULTS8-9 weeks after transplantation, the dropping times of hauling wire were 3.09 +/- 2.47, compared with that of the control dko mice(16.78 +/- 3.60), there are distinct differences. About electromyography items, the duration of active potential and amplitude of maxim contractions were (4.99 +/- 1.62) ms and(2872 +/- 1474.33) microV, compare with those of control dko mice(3.69 +/- 0.40) ms and(1210.0 +/- 551.0) microV, respectively, about 7% fibers of the muscle tissue of transplanted dko mice expressed dystrophin protein.

CONCLUSIONS8-9 weeks after transplanted with homology bone marrow stem cells, the locomotive function and electromyography items of transplanted dko mice were obviously improved, and about 7% muscle tissue fibers of the mice expressing dystrophin protein were observed. It suggested that there is an ideal prospect for DMD therapy with bone marrow stem cells transplantation.

Animals ; Cytoskeletal Proteins ; biosynthesis ; deficiency ; genetics ; Dystrophin ; deficiency ; genetics ; Hematopoietic Stem Cell Transplantation ; Membrane Proteins ; biosynthesis ; genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity ; Muscular Dystrophy, Duchenne ; physiopathology ; surgery ; Utrophin

OBJECTIVE: To determine the feasibility of using T2 mapping as a quantitative method to longitudinally follow the disease activity in children with Duchenne muscular dystrophy (DMD) who are treated with steroids. MATERIALS AND METHODS: Eleven boys with DMD (age range: 5-14 years) underwent evaluation with the clinical functional score (CFS), and conventional pelvic MRI and T2 mapping before and during steroid therapy. The gluteus muscle inflammation and fatty infiltration were evaluated on conventional MRI. The histograms and mean T2 relaxation times were obtained from the T2 maps. The CFS, the conventional MRI findings and the T2 values were compared before and during steroid therapy. RESULTS: None of the patients showed interval change of their CFSs. On conventional MRI, none of the images showed muscle inflammation. During steroid treatment, two boys showed increased fatty infiltration on conventional MRI, and both had an increase of the mean T2 relaxation time (p < 0.05). The remaining nine boys had no increase in fatty infiltration. Of these, three showed an increased mean T2 relaxation time (p < 0.05), two showed no change and four showed a decreased mean T2 relaxation time (p < 0.05). CONCLUSION: T2 mapping is a feasible technique to evaluate the longitudinal muscle changes in those children who receive steroid therapy for DMD. The differences of the mean T2 relaxation time may reflect alterations in disease activity, and even when the conventional MRI and CFS remain stable.
Adolescent ; Anti-Inflammatory Agents/therapeutic use ; Buttocks ; Child ; Child, Preschool ; Feasibility Studies ; Follow-Up Studies ; Humans ; Longitudinal Studies ; Magnetic Resonance Imaging/*methods ; Male ; Muscle Strength/drug effects ; Muscle, Skeletal/*drug effects/*physiopathology ; Muscular Dystrophy, Duchenne/*drug therapy/*physiopathology ; Observer Variation ; Pregnenediones/therapeutic use ; Prospective Studies