WorldWideScience

Sample records for progressive myocardial dystrophy

  1. Evaluation of myocardial involvement in Duchenne's progressive muscular dystrophy with thallium-201 myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Kawai, Naoki; Sotobata, Iwao; Okada, Mitsuhiro

    1985-01-01

    Myocardial involvement in progressive muscular dystrophy of the Duchenne type was evaluated in 19 patients using thallium-201 myocardial perfusion imaging. A qualitative analysis was performed from five projection images by three experienced physicians. Distinct perfusion defects were shown in 13 patients, especially in the LV posterolateral or posterior wall (11 patients). There was no significant relationship between the presence of perfusion defects and the skeletal muscle involvements or thoracic deformities assessed by transmission computed tomography. Extensive perfusion defects were shown in 2 patients who died of congestive heart failure 1 to 2 years after the scintigraphic study. Progression of the myocardial scintigraphic abnormalities were considered to be minimal in 7 of 9 patients who underwent two serial scintigraphic studies over 2 to 3 years. It was concluded that thallium myocardial perfusion imaging is a useful clinical technique to assess myocardial involvement in Duchenne's progressive muscular dystrophy. (author)

  2. Evaluation of myocardial involvement in Duchenne progressive muscular dystrophy with thallium-201 myocardial perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Naoki; Yamamoto, Shuhei; Okada, Mitsuhiro (Nagoya Univ. (Japan). Faculty of Medicine)

    1983-12-01

    Myocardial involvement in progressive muscular dystrophy of the Duchenne type was evaluated in 19 patients using thallium-201 myocardial perfusion imaging. The qualitative analysis was performed in anterior, 3 left anterior oblique and left lateral projection images by three experienced physicians. Distinct perfusion defects were shown in 13 patients, especially in LV posterolateral or posterior walls (11 patients). There was no significant relationship between the presence of perfusion defects and the skeletal muscle changes or thoracic deformities assessed by transmission computed tomography. Slightly increased thallium-201 activity in RV free wall and lungs was shown in nine and one patient, respectively. The extensive perfusion defects were shown in 2 patients who died of congestive heart failure 1 to 2 years after the scintigraphic study. The myocardial scintigraphic changes were considered to be minimal in 7 of 9 patients who underwent two serial scintigraphic studies in 2 to 3 years. It was concluded that the thallium myocardial perfusion imaging was a useful clinical technique to evaluate the cardiomyopathy in Duchenne progressive muscular dystrophy.

  3. Evaluation of myocardial involvement in Duchenne progressive muscular dystrophy with thallium-201 myocardial perfusion imaging

    International Nuclear Information System (INIS)

    Kawai, Naoki; Yamamoto, Shuhei; Okada, Mitsuhiro

    1983-01-01

    Myocardial involvement in progressive muscular dystrophy of the Duchenne type was evaluated in 19 patients using thallium-201 myocardial perfusion imaging. The qualitative analysis was performed in anterior, 3 left anterior oblique and left lateral projection images by three experienced physicians. Distinct perfusion defects were shown in 13 patients, especially in LV posterolateral or posterior walls (11 patients). There was no significant relationship between the presence of perfusion defects and the skeletal muscle changes or thoracic deformities assessed by transmission computed tomography. Slightly increased thallium-201 activity in RV free wall and lungs was shown in nine and one patient, respectively. The extensive perfusion defects were shown in 2 patients who died of congestive heart failure 1 to 2 years after the scintigraphic study. The myocardial scintigraphic changes were considered to be minimal in 7 of 9 patients who underwent two serial scintigraphic studies in 2 to 3 years. It was concluded that the thallium myocardial perfusion imaging was a useful clinical technique to evaluate the cardiomyopathy in Duchenne progressive muscular dystrophy. (author)

  4. Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy: A Randomized Clinical Trial.

    Science.gov (United States)

    Silva, Marly Conceição; Magalhães, Tiago Augusto; Meira, Zilda Maria Alves; Rassi, Carlos Henrique Reis Esselin; Andrade, Amanda Cristina de Souza; Gutierrez, Paulo Sampaio; Azevedo, Clerio Francisco; Gurgel-Giannetti, Juliana; Vainzof, Mariz; Zatz, Mayana; Kalil-Filho, Roberto; Rochitte, Carlos Eduardo

    2017-02-01

    In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), interventions reducing the progression of myocardial disease could affect survival. To assess the effect of early angiotensin-converting enzyme (ACE) inhibitor therapy in patients with normal left ventricular function on the progression of myocardial fibrosis (MF) identified on cardiovascular magnetic resonance (CMR). A randomized clinical trial conducted in 2 centers included 76 male patients with DMD or BMD undergoing 2 CMR studies with a 2-year interval for ventricular function and MF assessment. In a non-intent-to-treat trial, 42 patients with MF and normal left ventricular ejection fraction (LVEF) were randomized (1:1) to receive or not receive ACE inhibitor therapy. The study was conducted from June 26, 2009, to June 30, 2012. Data analysis was performed from June 30, 2013, to October 3, 2016. Randomization (1:1) to receive or not receive ACE inhibitor therapy. Primary outcome was MF progression from baseline to the 2-year CMR study. Of the 76 male patients included in the study, 70 had DMD (92%) and 6 had BMD (8%); mean (SD) age at baseline was 13.1 (4.4) years. Myocardial fibrosis was present in 55 patients (72%) and LV systolic dysfunction was identified in 13 patients (24%). Myocardial fibrosis at baseline was an independent indicator of lower LVEF at follow-up (coefficient [SE], -0.16 [0.07]; P = .03). Among patients with MF and preserved LVEF (42 [55%]), those randomized (21 patients in each arm) to receive ACE inhibitors demonstrated slower MF progression compared with the untreated group (mean [SD] increase of 3.1% [7.4%] vs 10.0% [6.2%] as a percentage of LV mass; P = .001). In multivariate analysis, ACE inhibitor therapy was an independent indicator of decreased MF progression (coefficient [SE], -4.51 [2.11]; P = .04). Patients with MF noted on CMR had a higher probability of cardiovascular events (event rate, 10 of 55 [18.2%] vs 0 of 21 [0%]; log-rank P = .04

  5. Dual myocardial scintigraphic imaging using 123I-BMIPP and 201Tl in patients with Duchenne's progressive muscular dystrophy

    International Nuclear Information System (INIS)

    Sasaki, Akira

    1996-01-01

    Dual single photon emission computed tomography (SPECT) was performed in 30 patients with Duchenne's muscular dystrophy (DMD) using 201 thallium (Tl) for myocardial perfusion 123 I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) for myocardial fatty acid metabolism scintigraphy. The left ventricle was divided into 9 regions, and accumulation of the radiotracers was assessed visually for each region to calculate defect score for each tracer. There was some degree of decrease in the myocardial accumulation of both tracers in all DMD patients. Reduced accumulation was most common at the apex (BMIPP, 70%; Tl, 63%), followed by the posterior wall, lateral wall, and anterior wall. It was less common on the apical side of the ventricular septum for both tracers (BMIPP, 3%; Tl, 17%). Accumulation of Tl was lower than BMIPP in 18/30 patients (60%) and higher in 9 (30%), while both tracers showed equal accumulation in 3 (10%). BMIPP showed higher accumulation than Tl in all regions but the septum. A significant negative correlation was found between the defect scores for both tracers and the left ventricular ejection fraction (LVEF) (r=-0.629 for Tl; r=-0.567 for BMIPP). The strongest negative correlation was that between the sum of the Tl and BMIPP defect scores and the LVEF (r=-0.681). Dual SPECT myocardial scintigraphy with Tl and BMIPP provided an accurate evaluation of the progression of cardiac lesions in DMD by detecting abnormalities of the myocardial metabolism of each substance thereby enabling the assessment of left ventricular function. (author)

  6. Management of myocardial damage in muscular dystrophy

    International Nuclear Information System (INIS)

    Tamura, Takuhisa

    2011-01-01

    Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin-converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future. (author)

  7. Detection of long-term progression of myocardial fibrosis in Duchenne muscular dystrophy in an affected family: A cardiovascular magnetic resonance study

    International Nuclear Information System (INIS)

    Walcher, Thomas; Steinbach, Peter; Spiess, Jochen; Kunze, Markus; Gradinger, Robert; Walcher, Daniel; Bernhardt, Peter

    2011-01-01

    Background: Detection of myocardial fibrosis and left ventricular dysfunction in Duchenne muscular dystrophy (DMD) is the corner stone for further therapeutic studies. Little is known about the ability of cardiac magnetic resonance imaging (CMR) to evaluate progression of myocardial fibrosis. Aim of our study was to provide CMR data in a previously genotyped DMD family and to evaluate whether progression of myocardial fibrosis could be visualized. Methods and results: DMD genotypes were available in 14 family members. CMR was performed in 4/5 carrier females, in 2/2 affected males and in one healthy family member with normal genotype. Functional images and late gadolinium enhanced (LGE) images in contiguous short-axis orientation were acquired at baseline and follow-up of 1231 days CMR examination could be repeated in three carrier females, in one affected male and in the healthy subject previously scanned. Mean decrease of left ventricular ejection fraction during the follow-up period was 10.5 ± 11.0%, mean progression of LGE volume 11.7 ± 9.5%. Conclusions: Myocardial fibrosis seems to occur prior to global left ventricular dysfunction in DMD diseased males and carrier females. CMR could be used to evaluate progression of myocardial fibrosis and left ventricular function and may thus serve as an important diagnostic tool in the evaluation of therapeutical options in DMD.

  8. Detection of long-term progression of myocardial fibrosis in Duchenne muscular dystrophy in an affected family: A cardiovascular magnetic resonance study

    Energy Technology Data Exchange (ETDEWEB)

    Walcher, Thomas [Department of Internal Medicine II, University of Ulm, Ulm (Germany); Steinbach, Peter [Institute of Human Genetics, University of Ulm, Ulm (Germany); Spiess, Jochen; Kunze, Markus; Gradinger, Robert; Walcher, Daniel [Department of Internal Medicine II, University of Ulm, Ulm (Germany); Bernhardt, Peter, E-mail: peter.bernhardt@uniklinik-ulm.de [Department of Internal Medicine II, University of Ulm, Ulm (Germany)

    2011-10-15

    Background: Detection of myocardial fibrosis and left ventricular dysfunction in Duchenne muscular dystrophy (DMD) is the corner stone for further therapeutic studies. Little is known about the ability of cardiac magnetic resonance imaging (CMR) to evaluate progression of myocardial fibrosis. Aim of our study was to provide CMR data in a previously genotyped DMD family and to evaluate whether progression of myocardial fibrosis could be visualized. Methods and results: DMD genotypes were available in 14 family members. CMR was performed in 4/5 carrier females, in 2/2 affected males and in one healthy family member with normal genotype. Functional images and late gadolinium enhanced (LGE) images in contiguous short-axis orientation were acquired at baseline and follow-up of 1231 days CMR examination could be repeated in three carrier females, in one affected male and in the healthy subject previously scanned. Mean decrease of left ventricular ejection fraction during the follow-up period was 10.5 {+-} 11.0%, mean progression of LGE volume 11.7 {+-} 9.5%. Conclusions: Myocardial fibrosis seems to occur prior to global left ventricular dysfunction in DMD diseased males and carrier females. CMR could be used to evaluate progression of myocardial fibrosis and left ventricular function and may thus serve as an important diagnostic tool in the evaluation of therapeutical options in DMD.

  9. Dual myocardial single photon emission computed tomography (SPECT) using thallium-201 and I-123-β-methyl-i-pentadecanoic acid in patients with Duchenne's progressive muscular dystrophy

    International Nuclear Information System (INIS)

    Shimoyama, Katsuya

    1999-01-01

    Dual single photon emission computed tomography (SPECT) was performed in 31 patients with Duchenne's progressive muscular dystrophy (DMD) using 123 I-β-methyl pentadecanoic acid (BMIPP) for myocardial fatty acid metabolism and 201 thallium (Tl)-chloride for myocardial perfusion. The left ventricle was divided into 9 segments, and accumulation of the radiotracers was assessed visually for each segment to calculate defect score for each tracer. There was some degree of decrease in myocardial accumulation of both tracers in all DMD patients. Reduced accumulation was most common at the apex (BMIPP: 67%, Tl: 63%), followed by the posterior wall, lateral wall, and anterior wall. On the other hand, reduced accumulation was less common at the septum. BMIPP showed a higher accumulation than Tl in all segments but the septum. When BMIPP defect score was larger than Tl defect score, BMIPP defect score tended to increase during 4 years follow-up (p Tl defect score revealed a slight fibrosis or normal myocardium. It can be concluded that the dual SPECT myocardial scintigraphy using BMIPP and Tl provides accurate information about disease progression of the heart in patients with DMD by detecting abnormalities of the myocardial metabolism of each substance, thereby enabling the assessment of left ventricular function. (author)

  10. Dual myocardial scintigraphic imaging using {sup 123}I-BMIPP and {sup 201}Tl in patients with Duchenne`s progressive muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Akira [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

    1996-03-01

    Dual single photon emission computed tomography (SPECT) was performed in 30 patients with Duchenne`s muscular dystrophy (DMD) using {sup 201} thallium (Tl) for myocardial perfusion {sup 123}I-{beta}-methyl-p-iodophenylpentadecanoic acid (BMIPP) for myocardial fatty acid metabolism scintigraphy. The left ventricle was divided into 9 regions, and accumulation of the radiotracers was assessed visually for each region to calculate defect score for each tracer. There was some degree of decrease in the myocardial accumulation of both tracers in all DMD patients. Reduced accumulation was most common at the apex (BMIPP, 70%; Tl, 63%), followed by the posterior wall, lateral wall, and anterior wall. It was less common on the apical side of the ventricular septum for both tracers (BMIPP, 3%; Tl, 17%). Accumulation of Tl was lower than BMIPP in 18/30 patients (60%) and higher in 9 (30%), while both tracers showed equal accumulation in 3 (10%). BMIPP showed higher accumulation than Tl in all regions but the septum. A significant negative correlation was found between the defect scores for both tracers and the left ventricular ejection fraction (LVEF) (r=-0.629 for Tl; r=-0.567 for BMIPP). The strongest negative correlation was that between the sum of the Tl and BMIPP defect scores and the LVEF (r=-0.681). Dual SPECT myocardial scintigraphy with Tl and BMIPP provided an accurate evaluation of the progression of cardiac lesions in DMD by detecting abnormalities of the myocardial metabolism of each substance thereby enabling the assessment of left ventricular function. (author).

  11. Dual myocardial single photon emission computed tomography (SPECT) using thallium-201 and I-123-{beta}-methyl-i-pentadecanoic acid in patients with Duchenne's progressive muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, Katsuya [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

    1999-10-01

    Dual single photon emission computed tomography (SPECT) was performed in 31 patients with Duchenne's progressive muscular dystrophy (DMD) using {sup 123}I-{beta}-methyl pentadecanoic acid (BMIPP) for myocardial fatty acid metabolism and {sup 201}thallium (Tl)-chloride for myocardial perfusion. The left ventricle was divided into 9 segments, and accumulation of the radiotracers was assessed visually for each segment to calculate defect score for each tracer. There was some degree of decrease in myocardial accumulation of both tracers in all DMD patients. Reduced accumulation was most common at the apex (BMIPP: 67%, Tl: 63%), followed by the posterior wall, lateral wall, and anterior wall. On the other hand, reduced accumulation was less common at the septum. BMIPP showed a higher accumulation than Tl in all segments but the septum. When BMIPP defect score was larger than Tl defect score, BMIPP defect score tended to increase during 4 years follow-up (p<0.042). However, when Tl defect score was larger than BMIPP defect score, an increase in Tl defect score was slight. A significant negative correlation was found between the sum of the BMIPP and Tl defect scores and the left ventricular ejection fraction (LVEF) (r=0.66, p<0.0001). According to the histo-pathological study of two autopsied hearts, severe myocardial fibrosis was seen in segments with fixed perfusion defect. In addition, the mismatched segments of BMIPP defect score > Tl defect score revealed a slight fibrosis or normal myocardium. It can be concluded that the dual SPECT myocardial scintigraphy using BMIPP and Tl provides accurate information about disease progression of the heart in patients with DMD by detecting abnormalities of the myocardial metabolism of each substance, thereby enabling the assessment of left ventricular function. (author)

  12. Mitochondrial disorders in progressive muscular dystrophies

    Directory of Open Access Journals (Sweden)

    D. A. Kharlamov

    2014-01-01

    Full Text Available The literature review gives data on the role of mitochondrial disorders in the pathogenesis of different progressive muscular dystrophies. It describes changes in Duchenne, limb-girdle, facial scapulohumeral (Landuzi—Degerina muscular dystrophies. The review is based on both clinical and experimental animal studies. Along with the implication of mitochondria in the pathogenesis of the diseases, it describes muscular dystrophy treatment options compensating for energy disorders and overcoming oxidative stress and mitochondrial dysfunction. Mitochondrial studies in different muscle diseases hand physicians treatment modalities that fail to lead to recovery, but compensate for disorders caused by mutations in the genetic apparatus. 

  13. Sequential change of cardiomyopathy of Duchenne muscular dystrophy by 201Tl myocardial SPECT

    International Nuclear Information System (INIS)

    Ono, Seiji; Sugimoto, Seiichirou; Inoue, Kenjirou; Jinnouchi, Seishi; Hoshi, Hiroaki; Watanabe, Katsushi.

    1989-01-01

    201 Tl myocardial SPECT were performed to evaluate of cardiomyopathy in Duchenne type of progressive muscular dystrophy (DMD). Follow up SPECT images of the same patients were also obtained about 1 year after the first scan. Cases subjected to study were 10 DMD. At the first study the hypoperfusion area of the left ventricular muscle were observed in 6 cases (60%) out of 10. At the second study the hypoperfusion areas became wider and lower in 4 out of 6 cases (66.7%). The new hypoperfusion area which was not demonstrated at the first study was observed at the second study in one case of these cases. These results suggested that the positive rate of cardiomyopathy in DMD by 201 Tl myocardial SPECT was high, and 201 Tl myocardial SPECT is a useful examination to detect the change of myocardial damage in DMD. (author)

  14. Sequential change of cardiomyopathy of Duchenne muscular dystrophy by /sup 201/Tl myocardial SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Seiji; Sugimoto, Seiichirou; Inoue, Kenjirou; Jinnouchi, Seishi; Hoshi, Hiroaki; Watanabe, Katsushi.

    1989-03-01

    /sup 201/Tl myocardial SPECT were performed to evaluate of cardiomyopathy in Duchenne type of progressive muscular dystrophy (DMD). Follow up SPECT images of the same patients were also obtained about 1 year after the first scan. Cases subjected to study were 10 DMD. At the first study the hypoperfusion area of the left ventricular muscle were observed in 6 cases (60%) out of 10. At the second study the hypoperfusion areas became wider and lower in 4 out of 6 cases (66.7%). The new hypoperfusion area which was not demonstrated at the first study was observed at the second study in one case of these cases. These results suggested that the positive rate of cardiomyopathy in DMD by /sup 201/Tl myocardial SPECT was high, and /sup 201/Tl myocardial SPECT is a useful examination to detect the change of myocardial damage in DMD. (author).

  15. Cardiac involvement of progressive muscular dystrophy (Becker type, Limb-girdle type and Fukuyama type) evaluated by radionuclide method

    International Nuclear Information System (INIS)

    Nagamachi, Shigeki; Inoue, Kenjiro; Jinnouchi, Seishi; Hoshi, Hiroaki; Ono, Seiji; Ohnishi, Takashi; Futami, Shigemi; Watanabe, Katsushi; Hayashi, Tohru

    1994-01-01

    Tl-201 SPECT and Tc-99m-Human serum albumin (HSA) multigated radionuclide ventriculography were performed on 11 patients with progressive muscular dystrophy (Becker type 2, Fukuyama type 2, Limb-girdle type 7) to evaluate myocardial involvement. Hypoperfusion was detected in 8 patients on Tl-201 SPECT. Decreases in both systolic function (left ventricular ejection fraction; LVEF) and diastolic function (peak filling rate; PFR) were also seen in these patients. A high incidence of myocardial involvement of these kinds of progressive muscular dystrophy was suggested. (author)

  16. Cardiac involvement of progressive muscular dystrophy (Becker type, Limb-girdle type and Fukuyama type) evaluated by radionuclide method

    Energy Technology Data Exchange (ETDEWEB)

    Nagamachi, Shigeki; Inoue, Kenjiro; Jinnouchi, Seishi; Hoshi, Hiroaki; Ono, Seiji; Ohnishi, Takashi; Futami, Shigemi; Watanabe, Katsushi; Hayashi, Tohru [Miyazaki Medical Coll., Kiyotake (Japan)

    1994-02-01

    Tl-201 SPECT and Tc-99m-Human serum albumin (HSA) multigated radionuclide ventriculography were performed on 11 patients with progressive muscular dystrophy (Becker type 2, Fukuyama type 2, Limb-girdle type 7) to evaluate myocardial involvement. Hypoperfusion was detected in 8 patients on Tl-201 SPECT. Decreases in both systolic function (left ventricular ejection fraction; LVEF) and diastolic function (peak filling rate; PFR) were also seen in these patients. A high incidence of myocardial involvement of these kinds of progressive muscular dystrophy was suggested. (author).

  17. Evaluation of cardiomyopathy in Duchenne muscular dystrophy by Tl-201 myocardial SPECT

    International Nuclear Information System (INIS)

    Jinnouchi, Seishi; Asai, Junko; Inoue, Kenjirou; Hoshi, Hiroaki; Watanabe, Katsushi.

    1985-01-01

    Clinical evaluation of Tl-201 myocardial SPECT in patients with cardiomyopathy of Duchenne type progressive muscular dystrophy (DMD) was reported. Cases subjected to study were 14 DMD and 8 normal. Using a rotating gamma camera system (ZLC7500 and Scintipac 70A), SPECT data were collected for 16 minutes (32 angles x 30 sec/angle, 180 0 ). The hypoperfusion areas of the left ventricular muscle were observed in 10 patients (71 %), which was in posterior wall (71 %), inferior wall (57 %), lateral and anterior wall (43 %) in the order of frequency. The hypoperfusion area became wider with age and stage, exept for some patients. It was suggested that myocardial degeneration in DMD started in posterior wall and then spread in other areas. For the purpose of quantitative evaluation of myocardial damage, Tl-201 myocardial uptake ratio (MUR) and left ventricular muscle volume (LVMV) were calculated using the results obtained by phantom studies. MUR and LVMV were higher in DMD than those of normal individuals (3.6 +- 1.0 %: 2.7 +- 0.3 %, p < 0.05, 190.2 +- 67.5 ml: 157.8 +- 21.5 ml, n.s., respectively). (author)

  18. Evaluation of myocardial damage in Duchenne's muscular dystrophy with thallium-201 myocardial SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Takuhisa; Shibuya, Noritoshi (Kawatana National Hospital, Nagasaki (Japan)); Hashiba, Kunitake; Oku, Yasuhiko; Mori, Hideki; Yano, Katsusuke

    1993-01-01

    Myocardial damage and cardiopulmonary functions in patients with Duchenne's muscular dystrophy (DMD) were assessed using thallium-201 myocardial single-photon emission computed tomography (SPECT) and technetium-99m multigated radionuclide angiography. Twenty-five patients with DMD were divided into 4 groups according to percent of perfusion defect (%PD) calculated by the bull's-eye method and age. PD was detected in 24 (96.0%) of 25 patients with DMD, and it spread from the left ventricular lateral wall to the anterior wall and/or interventricular septum. PD was detected even in a 6-year-old DMD boy. Patients in Group I (%PD[>=]10% and age<15 years old) were shown to have a higher risk of left-sided heart failure without respiratory failure. Patients in Group II (%PD[>=]10 and age[>=]15) showed decreased pulmonary function and worsened arterial blood gas values as compared with Group IV (%PD<10 and age[>=]15). There was no significant difference in cardiac function among the 4 groups. It is postulated that myocardial damage in Group II patients is dependent primarily on a deficiency of dystrophin and on chronic respiratory failure, and that some of them are at risk of cardiopulmonary failure. It is concluded that myocardial SPECT is useful for the early diagnosis of myocardial damage and evaluation of cardiopulmonary function in DMD patients. (author).

  19. Evaluation of myocardial damage in Duchenne's muscular dystrophy with thallium-201 myocardial SPECT

    International Nuclear Information System (INIS)

    Tamura, Takuhisa; Shibuya, Noritoshi; Hashiba, Kunitake; Oku, Yasuhiko; Mori, Hideki; Yano, Katsusuke.

    1993-01-01

    Myocardial damage and cardiopulmonary functions in patients with Duchenne's muscular dystrophy (DMD) were assessed using thallium-201 myocardial single-photon emission computed tomography (SPECT) and technetium-99m multigated radionuclide angiography. Twenty-five patients with DMD were divided into 4 groups according to percent of perfusion defect (%PD) calculated by the bull's-eye method and age. PD was detected in 24 (96.0%) of 25 patients with DMD, and it spread from the left ventricular lateral wall to the anterior wall and/or interventricular septum. PD was detected even in a 6-year-old DMD boy. Patients in Group I (%PD≥10% and age<15 years old) were shown to have a higher risk of left-sided heart failure without respiratory failure. Patients in Group II (%PD≥10 and age≥15) showed decreased pulmonary function and worsened arterial blood gas values as compared with Group IV (%PD<10 and age≥15). There was no significant difference in cardiac function among the 4 groups. It is postulated that myocardial damage in Group II patients is dependent primarily on a deficiency of dystrophin and on chronic respiratory failure, and that some of them are at risk of cardiopulmonary failure. It is concluded that myocardial SPECT is useful for the early diagnosis of myocardial damage and evaluation of cardiopulmonary function in DMD patients. (author)

  20. The imaging research of myocardial damage in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Fu Peng; Wei Lingge; Hu Jing; Huang Jianmin; Liu Xiaomei

    2011-01-01

    It is common that Duchenne muscular dystrophy (DMD) patients can suffer from cardiac damage, which performed variously. Cardiac damage in DMD often be paid no attention in early stage,since the clinical symptoms is slight. With the decline of cardiac function, the quality of life, treatment and rehabilitation training of patients will be affected significantly. Furthermore, the progress of the disease will be speeded up and the difficulty of treatment will be increased. Therefore, there will be important significance in delaying the progression of cardiac damage and prolonging the life of patients by the early diagnosis and intervention treatment of cardiac damage in DMD. For the convenience of the clinician to choose suitable imaging methods, to improve the cardiac damage in patients of DMD, imaging researches which are applied to the DMD cardiac damage are reviewed. (authors)

  1. Myocardial fibrosis burden predicts left ventricular ejection fraction and is associated with age and steroid treatment duration in duchenne muscular dystrophy.

    Science.gov (United States)

    Tandon, Animesh; Villa, Chet R; Hor, Kan N; Jefferies, John L; Gao, Zhiqian; Towbin, Jeffrey A; Wong, Brenda L; Mazur, Wojciech; Fleck, Robert J; Sticka, Joshua J; Benson, D Woodrow; Taylor, Michael D

    2015-03-26

    Patients with Duchenne muscular dystrophy exhibit progressive cardiac and skeletal muscle dysfunction. Based on prior data, cardiac dysfunction in Duchenne muscular dystrophy patients may be influenced by myocardial fibrosis and steroid therapy. We examined the longitudinal relationship of myocardial fibrosis and ventricular dysfunction using cardiac magnetic resonance in a large Duchenne muscular dystrophy cohort. We reviewed 465 serial cardiac magnetic resonance studies (98 Duchenne muscular dystrophy patients with ≥4 cardiac magnetic resonance studies) for left ventricular ejection fraction (LVEF) and presence of late gadolinium enhancement (LGE), a marker for myocardial fibrosis. LVEF was modeled by examining LGE status, myocardial fibrosis burden (as assessed by the number of LGE-positive left ventricular segments), patient age, and steroid treatment duration. An age-only model demonstrated that LVEF declined 0.58 ± 0.10% per year. In patients with both LGE-negative and LGE-positive studies (n=51), LVEF did not decline significantly over time if LGE was absent but declined 2.2 ± 0.31% per year when LGE was present. Univariate modeling showed significant associations between LVEF and steroid treatment duration, presence of LGE, and number of LGE-positive left ventricular segments; multivariate modeling showed that LVEF declined by 0.93 ± 0.09% for each LGE-positive left ventricular segment, whereas age and steroid treatment duration were not significant. The number of LGE-positive left ventricular segments increased with age, and longer steroid treatment duration was associated with lower age-related increases. Progressive myocardial fibrosis, as detected by LGE, was strongly correlated with the LVEF decline in Duchenne muscular dystrophy patients. Longer steroid treatment duration was associated with a lower age-related increase in myocardial fibrosis burden. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley

  2. Detection of regional derangements in myocardial metabolism by positron computed tomography in Duchenne's muscular dystrophy

    International Nuclear Information System (INIS)

    Henze, E.; Schelbert, H.R.; Perloff, J.K.; Schwaiger, M.; Phelps, M.E.

    1982-01-01

    Duchenne's Muscular Dystrophy is unique in genetically targeting for disease a specific region of myocardium: the postero-basal left ventricular wall. Postmortem examinations revealed focal fibrous degenerations in the postero-basal segment, while the coronary arteries were usually not affected. A predystrophic metabolic fault has been postulated for this region. This hypothesis was tested with positron computed tomography as a new means for the noninvasive study of regional myocadial perfusion and metabolism and to determine the incidence of regional and global left ventricular dysfunction and perfusion abnormalities using Thallium-201 and gated blood pool imaging. Myocardial perfusion was evaluated with N-13 ammonia while regional myocardial glucose uptake was studied with the glucose analog F-18 DG. The sensitivity of each diagnostic test for detecting cardiac involvement in Duchenne's Muscular Dystrophy was evaluated. It was highest for ammonia and glucose imaging and it was low for Thallium and radionuclide blood pool imaging

  3. The pyrophosphate heart scintigram in children with progressive muscular dystrophy

    International Nuclear Information System (INIS)

    Duska, F.; Nesvadba, Z.; Zdansky, P.; Novak, J.; Kubicek, J.; Kafka, P.; Vizda, J.; Mazurova, Y.; Karlova Univ., Hradec Kralove; Karlova Univ., Hradec Kralove

    1984-01-01

    A pyrophosphate heart scintigram was obtained in 16 boys with progressive muscular dystrophy Duchenne. All of them showed pathological ECG findings and high plasma levels of CK, AST, ALT and LD. In 4 patients the scintigram was distinctly positive and in further 3 it reached borderline values. The remaining 9 boys had normal scintigraphic findings. Those with a positive heart scintigram had very high plasma levels of the enzymes under study which was suggestive of current progression of the disease. There was, however, no relation between heart scintigraphy and the affliction of the skeletal muscles expressed by means of an index. (orig.) [de

  4. Pyrophosphate heart scintigram in children with progressive muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Duska, F; Nesvadba, Z; Zdansky, P; Novak, J; Kubicek, J; Kafka, P; Vizda, J; Mazurova, Y

    1984-08-01

    A pyrophosphate heart scintigram was obtained in 16 boys with progressive muscular dystrophy Duchenne. All of them showed pathological ECG findings and high plasma levels of CK, AST, ALT and LD. In 4 patients the scintigram was distinctly positive and in further 3 it reached borderline values. The remaining 9 boys had normal scintigraphic findings. Those with a positive heart scintigram had very high plasma levels of the enzymes under study which was suggestive of current progression of the disease. There was, however, no relation between heart scintigraphy and the affliction of the skeletal muscles expressed by means of an index.

  5. Progress study of the cardiac damage in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    ZHANG Yao

    2013-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is a fatal muscular disease with rapid progression in children. Most patients die of respiratory and circulatory failure before the age of 20 if there is no systematic treatment. Now the heart problem in this disease has become increasingly prominent, and is thought to be closely associated with certain dystrophin exon deletion. We would like to review the epidemiology, relevance of dystrophin, pathogenesis, clinical manifestations and pathological features, as well as early prevention and treatment of DMD.

  6. Case of early pelviolumeral progressive muscular dystrophy associated with marked heart affection

    International Nuclear Information System (INIS)

    Gor'kova, N.B.; Starykh, L.M.; Karpova, L.E.

    1991-01-01

    A case of early pelviolumeral progressive muscular dystrophy detected in childhood and associated with marked heart affection is described. Patient underwent multimodality examination, including ECG, ultrasonography, roentgenography. It is shown that patients with progressive muscular dystrophy should receive medical supervision and treatment of both neuropathologist and therapist

  7. Evaluation of myocardial involvement in muscular dystrophy with Thallium-201 emission computed tomography

    International Nuclear Information System (INIS)

    Yamamoto, S.; Kawai, N.; Matsushima, H.; Okada, M.; Yamauchi, K.; Yokota, M.; Hayashi, H.; Sotobata, I.; Sakuma, S.

    1985-01-01

    The clinical usefulness of quantitative analysis of thallium-201 emission computed tomography (ECT) for evaluation of left ventricular myocardial fibrosis was assessed on 45 patients with Duchenne(D), facioscapulohumeral(FSH), limbgirdle(LG) and myotonic(M) dystrophy. Trans-,long- and short-axial images were interpreted quantitatively using circumferential profile analysis, and the fibrotic tissue size (%FIB) was estimated by integration of hypoperfused areas in 6 to 8 consecutive short-axial slices. Lung/mediastinum count ratios (L/M ratio) were also assessed. Distinct ECT defects were found in 42 patients (all cases of D, FSH and LG, and 2 of 5 MTs). ECT defects were observed specifically in the posterolateral wall (71%) and apex (58%) in D, and were scattered in all LV walls in FSHG, LG and MT. ECG and VCG underestimated the extent of myocardial fibrosis in 17 patients (40%). Percent FIBs coincided with fibrotic tissue sizes proven by autopsy. Body-surface ECG should be influenced by cardiac position and rotation in the thorax, which were often observed in these disease entities. These factors were also assessed with ECT. The authors conclude; ECT to be useful for non-invasive evaluation of myocardial fibrosis in patients with various types of muscular dystrophy

  8. Evaluation of myocardial involvement in muscular dystrophy with thallium-201 emission computed tomography

    International Nuclear Information System (INIS)

    Yamamoto, Shuhei; Sotobata, Iwao; Indo, Toshikatsu; Matsuoka, Yukihiko; Kawai, Naoki; Matsushima, Hideo; Suzuki, Akio; Abe, Tetsutaro; Sakuma, Sadayuki

    1986-01-01

    The clinical usefulness of thallium-201 myocardial perfusion scanning with emission computed tomography (ECT) for evaluation of left ventricular myocardial fibrosis was assessed on 47 patients with Duchenne (DMD), facioscapulohumeral (FSH), limb-girdle (LG) and myotonic (MT) dystrophy. Trans-, long- and short-axial images were interpreted quantitatively by circumferential profile analysis, and the fibrotic tissue size (%FIB) was estimated by integration of hypoperfused areas in 6 to 8 consecutive short-axial slices. Lung/mediastinum count ratios (L/M ratio), LV cavity dilatation, aneurysm formation and cardiac malrotations were also assessed with ECT. Distinct ECT perfusion defect was observed in 26 of 29 DMDs, and in 11 of 18 patients with other types. Perfusion defect was demonstrated in 95 of total 235 segments, and was observed specifically in the posterior wall (82 %) and the apex (65 %) in DMD, and was scattered in all LV wall segments in FSH, LG, and MT. Percent FIB correlated significantly with L/M ratio (r = 0.82, p < 0.01), and did not with age or clinical stage score. ECT showed marked LV dilatation in 7, apical aneurysm in 5 and cardiac malrotation in 23 of the 47 patients. In conclusion, ECT was considered to be a useful clinical means of evaluating myocardial involvement in patients with muscular dystrophy. (author)

  9. Progress toward Gene Therapy for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Chamberlain, Joel R; Chamberlain, Jeffrey S

    2017-05-03

    Duchenne muscular dystrophy (DMD) has been a major target for gene therapy development for nearly 30 years. DMD is among the most common genetic diseases, and isolation of the defective gene (DMD, or dystrophin) was a landmark discovery, as it was the first time a human disease gene had been cloned without knowledge of the protein product. Despite tremendous obstacles, including the enormous size of the gene and the large volume of muscle tissue in the human body, efforts to devise a treatment based on gene replacement have advanced steadily through the combined efforts of dozens of labs and patient advocacy groups. Progress in the development of DMD gene therapy has been well documented in Molecular Therapy over the past 20 years and will be reviewed here to highlight prospects for success in the imminent human clinical trials planned by several groups. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  10. Tl-201 myocardial SPECT in patients with Duchenne's muscular dystrophy: A long-term follow-up

    International Nuclear Information System (INIS)

    Nagamachi, S.; Jinnouchi, S.; Ono, S.; Hoshi, H.; Inoue, K.; Watanabe, K.

    1989-01-01

    Tl-201 SPECT was used to evaluate myocardial involvement in 13 patients with Duchenne's muscular dystrophy. Serial studies of 9 patients were done at two-year intervals. The hypoperfused areas of the left ventricle became more prominent with age and severity

  11. Study progress of cardiac MRI technology in assessment of myocardial viability after myocardial infarction

    International Nuclear Information System (INIS)

    Wang Jing; Zhang Hao

    2013-01-01

    Acute myocardial infarction (AMI) is one of the most common diseases that cause disability and death around the world. Correctly and effectively assessing the myocardial viability after myocardial infarction can reduce the disabled rate and mortality rate. At present, many methods could be used to assess myocardial viability. The cardiac magnetic resonance imaging (CMR) technology has a lot of advantages compared to other methods. In this paper, we reviewed the research progress of CMR in assessment of myocardial viability after myocardial infarction, and compared CMR with other technologies. (authors)

  12. Thallium-201 single photon emission computed tomography (SPECT) in patients with Duchenne's progressive muscular dystrophy. A histopathologic correlation study

    International Nuclear Information System (INIS)

    Nishimura, Toru; Yanagisawa, Atsuo; Sakata, Konomi; Shimoyama, Katsuya; Yoshino, Hideaki; Ishikawa, Kyozo; Sakata, Hitomi; Ishihara, Tadayuki

    2001-01-01

    The pathomorphologic mechanism responsible for abnormal perfusion imaging during thallium-201 myocardial single photon emission computed tomography ( 201 Tl-SPECT) in patients with Duchenne's progressive muscular dystrophy (DMD) was investigated. Hearts from 7 patients with DMD were evaluated histopathologically at autopsy and the results correlated with findings on initial and delayed resting 201 Tl-SPECT images. The location of segments with perfusion defects correlated with the histopathologically abnormal segments in the hearts. Both the extent and degree of myocardial fibrosis were severe, especially in the posterolateral segment of the left ventricle. Severe transmural fibrosis and severe fatty infiltration were common in segments with perfusion defects. In areas of redistribution, the degree of fibrosis appeared to be greater than in areas of normal perfusion; and intermuscular edema was prominent. Thus, the degree and extent of perfusion defects detected by 201 Tl-SPECT were compatible with the histopathology. The presence of the redistribution phenomenon may indicate ongoing fibrosis. Initial and delayed resting 201 Tl-SPECT images can predict the site and progress of myocardial degeneration in patients with DMD. (author)

  13. Progressive muscular dystrophy: Duchenne type. Controversies of the kinesitherapy treatment

    Directory of Open Access Journals (Sweden)

    Ana Valéria de Araujo Leitão

    Full Text Available The authors carried out a study of children with progressive muscular dystrophy of Duchenne type (DMD, giving special attention to physiatrical follow-up, having in mind that the practice of exercises has been debated very much in the specialized literature. The goal of this study is to try to settle the limits for the utilization of kinesitherapy which should be applied only in specific situations, such as: after skeletal muscular trauma or when the respiratory system is at risk. In this situation the physiatrical procedure would be to restrict physical activity, with early use of wheelchairs and the exclusion of the use of orthoses for orthostatism. DMD, at present, has been considered a result of duplication (60%, deletion (5 to 6% or point mutations at gen Xp21 (Zatz, 1994, that codifies a protein called Dystrophin ( Hoffman et al., 1987. Dystrophin is a cytoskeletal sarcolemmic protein that constitutes about .002% of the total protein of the muscle, present in skeletal fibers concentrated in muscle tendinous joints, which supplies mechanical reinforcement to the surface of the membrane during stretching and shortening physical activity. This protein is absent in DMD cases, wherefore, the sarcolemma undergoes a segmentary necrosis losing its contractile property during eccentric and concentric physical activity. The importance of physiatrical follow-up for DMD patients is to avoid deformities and tendon shortening, to ameliorate the patient's quality of life, to provide respiratory assistance and general couseling to members of the patient's family. The objective of this study is to try to clarify the risks and possibilities of kinesitherapy applied to DMD cases.

  14. Congenital hereditary endothelial dystrophy with progressive sensorineural deafness (Harboyan syndrome

    Directory of Open Access Journals (Sweden)

    Abramowicz Marc

    2008-10-01

    Full Text Available Abstract Harboyan syndrome is a degenerative corneal disorder defined as congenital hereditary endothelial dystrophy (CHED accompanied by progressive, postlingual sensorineural hearing loss. To date, 24 cases from 11 families of various origin (Asian Indian, South American Indian, Sephardi Jewish, Brazilian Portuguese, Dutch, Gypsy, Moroccan, Dominican have been reported. More than 50% of the reported cases have been associated with parental consanguinity. The ocular manifestations in Harboyan syndrome include diffuse bilateral corneal edema occurring with severe corneal clouding, blurred vision, visual loss and nystagmus. They are apparent at birth or within the neonatal period and are indistinguishable from those characteristic of the autosomal recessive CHED (CHED2. Hearing deficit in Harboyan is slowly progressive and typically found in patients 10–25 years old. There are no reported cases with prelinglual deafness, however, a significant hearing loss in children as young as 4 years old has been detected by audiometry, suggesting that hearing may be affected earlier, even at birth. Harboyan syndrome is caused by mutations in the SLC4A11 gene located at the CHED2 locus on chromosome 20p13-p12, indicating that CHED2 and Harboyan syndrome are allelic disorders. A total of 62 different SLC4A11 mutations have been reported in 98 families (92 CHED2 and 6 Harboyan. All reported cases have been consistent with autosomal recessive transmission. Diagnosis is based on clinical criteria, detailed ophthalmological assessment and audiometry. A molecular confirmation of the clinical diagnosis is feasible. A variety of genetic, metabolic, developmental and acquired diseases presenting with clouding of the cornea should be considered in the differential diagnosis (Peters anomaly, sclerocornea, limbal dermoids, congenital glaucoma. Audiometry must be performed to differentiate Harboyan syndrome from CHED2. Autosomal recessive types of CHED (CHED2 and

  15. Ultrastructural and ERG findings in progressive rod-cone dystrophy in a litter of Labrador retrievers.

    Science.gov (United States)

    Raitta, C; Kommonen, B; Ulshafer, R; Karhunen, U

    1991-02-01

    Early ultrastructural findings of a progressive photoreceptor dystrophy and corresponding ERG findings are reported in 3 Labrador Retrievers from a litter of 7 pups bred from 2 dogs clinically and electroretinographically affected with generalized progressive retinal dystrophy. The pups were euthanized at 5, 11 and 15 months post partum. The most prominent ultrastructural finding was photoreceptor dystrophy. At 5 months the outer nuclear layer (ONL) consisted of 8-10 layers and seemed reduced in thickness, pyknotic nuclei were seen in this layer. The receptor outer segments (OS) were short and swollen. Some disorientation of OS discs occurred. In the 11-months specimen 7-8 ONL layers were identified. Overall thinning of the neuro-retina had occurred and fewer receptors compared to the 5-months specimen were present. By 15 months the ONL was further reduced to about 4 layers. Enlarged internuclear spaces were present in the ONL as well as around inner segments (IS). Phagocytic cells were frequent among remains of OS. The pigment epithelium appeared normal. The dark adapted ERG b-wave amplitudes and photopic 30 Hz flicker responses were low in comparison to controls of the same breed, and decreased with age. The condition represents a progressive rod-cone dystrophy which shares similarities with primary receptor dystrophy in man such as retinitis pigmentosa.

  16. Myocardial involvement in muscular dystrophy evaluated by thallium-201 emission computed tomography

    International Nuclear Information System (INIS)

    Yamamoto, Shuhei; Matsushima, Hideo; Kawai, Naoki; Sotobata, Iwao

    1986-01-01

    The clinical usefulness of thallium-201 myocardial emission computed tomography (ECT) for evaluating left ventricular myocardial fibrosis was assessed in 47 patients with Duchenne (MD), facio-scapulo-humeral (FSH), limb-girdle (LG) and myotonic (MT) dystrophy. 1. Trans-, long- and short-axial images were interpreted quantitatively by circumferential profile analysis, and the extent of fibrotic tissue (%FIB) was estimated by integrating hypoperfused areas in six to eight consecutive short-axial slices. Lung/mediastinum count ratio (L/M ratio), LV cavity dilatation, aneurysm formation and cardiac malrotation were also assessed with ECT. 2. Distinct ECT defects were demonstrated in 95 of a total of 235 LV segments (40 %) and in 37 of 47 cases (85 % of DMD, 71 % of FSH, 50 % of MT and 60 % of LG). They were observed specifically in the posterior wall (82 %) and the apex (65 %) in DMD, and were scattered in all LV wall segments in FSH, LG, and MT. 3. There was a significant correlation between %FIB and the L/M ratio (r = 0.79, p < 0.001), and the L/M ratio was significantly higher in DMD than in MT (0.67 ± 0.36 vs 0.34 ± 0.25, p < 0.05). 4. ECT showed marked LV dilatation in seven (15 %), apical aneurysm in five (11 %) and vertical heart in 12 (26 %) of the 47 patients. 5. There were no significant correlations between age or clinical stage scores and numbers of defect segments or %FIB in each group. 6. During the one-year follow-up period of these patients, a DMD boy with the largest %FIB (54 %) and the highest L/M ratio (1.4) together with LV dilatation had complications of refractory heart failure and he died eight months following the ECT examination. 7. Thallium-201 planar imaging and standard 12-lead ECG underestimated the perfusion defects which were evaluated with ECT. (author)

  17. Progression of cardiac involvement in patients with limb-girdle type 2 and Becker muscular dystrophies

    DEFF Research Database (Denmark)

    Petri, Helle; Sveen, Marie-Louise; Thune, Jens Jakob

    2015-01-01

    AIM: To assess the degree and progression of cardiac involvement in patients with limb-girdle type 2 (LGMD2) and Becker muscular dystrophies (BMD). METHODS: A follow-up study of 100 LGMD2 (types A-L) and 30 BMD patients assessed by electrocardiogram (ECG) and echocardiography, supplemented...

  18. Quantitative computed tomography for objectifying disseminated skeletal muscles alterations in female conductors of progressive muscular dystrophy

    International Nuclear Information System (INIS)

    Huppert, P.

    1987-01-01

    The detection of early morphologic changes, such as circumscribed infiltrations of adipose connective tissue into the muscles of female conductors of progressive muscular dystrophy requires quantitative planimetric methods. For a reliable interpretation of the results the dependence of the fat content of the musculature on age and physical constitution of the patient must be taken into consideration in each individual case. (author)

  19. Myocardial Contractile Dysfunction is Present Without Histopathology in a Mouse Model of Limb-Girdle Muscular Dystrophy-2F and is Prevented after Claudin-5 Virotherapy

    Directory of Open Access Journals (Sweden)

    Nima Milani-Nejad

    2016-12-01

    Full Text Available AbstractMutations in several members of the dystrophin glycoprotein complex lead to skeletal and cardiomyopathies. Cardiac care for these muscular dystrophies consists of management of symptoms with standard heart medications after detection of reduced whole heart function. Recent evidence from both Duchenne muscular dystrophy patients and animal models suggests that myocardial dysfunction is present before myocardial damage or deficiencies in whole heart function, and that treatment prior to heart failure symptoms may be beneficial. To determine whether this same early myocardial dysfunction is present in other muscular dystrophy cardiomyopathies, we conducted a physiological assessment of cardiac function at the tissue level in the δ-sarcoglycan null mouse model (Sgcd-/- of Limb-girdle muscular dystrophy type 2F. Baseline cardiac contractile force measurements using ex vivo intact linear muscle preparations, were severely depressed in these mice without the presence of histopathology. Virotherapy with claudin-5 prevents the onset of cardiomyopathy in another muscular dystrophy model. After virotherapy with claudin-5, the cardiac contractile force deficits in Sgcd-/- mice are no longer significant. These studies suggest that screening Limb-girdle muscular dystrophy patients using methods that detect earlier functional changes may provide a longer therapeutic window for cardiac care.

  20. The analysis of the clinical and tool parameters characterizing a cardiomyopathyat various forms of the progressing muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Poverennova I.E.

    2017-03-01

    Full Text Available Purpose: studying of clinical and tool characteristics of cardiomyopathies at various forms of the progressing muscular dystrophies. Material and methods. There had been 103 patients with hereditary forms of the progressing muscular dystrophies examined, among which 35 persons were with Duchenne muscular dystrophy, 28 with an atrophic myo-tonia, and 40 with a limb girdle dystrophy is conducted. Assessment of clinical and tool features of cardiomyopathies at these types of the hereditary progressing muscular dystrophies had been carried out. Results. In the group of patients with diffusion damage of a myocardium in the form of dystrophic violations had been revealed. Existence of a negative tooth of T in some assignments and lengthenings of an interval of QT is noted. With a dystrophic myotonia violation of a warm rhythm occurred at patients by 87 times more often than in the group of comparison. Violation of a rhythm of heart in group of patients with a limb girdle dystrophy came to light 91 times more often in reference to the group of comparison. Conclusion. Violations in a cardiovascular system at Duchenne muscular dystrophy are preferentially diffusion changes in a myocardium. At a dystrophic myotonia and a limb girdle dystrophy cardial violations concern mainly excitability and the conductivity of heart which are the main reason of developing of this disease at these patients.

  1. Effect of cellular therapy in progression of Becker’s muscular dystrophy: a case study

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2016-03-01

    Full Text Available Becker muscular dystrophy (BMD is an inherited disorder due to deletions of the dystrophin gene that leads to muscle weakness. Effects of bone marrow mononuclear cell (BMMNC transplantation in Muscular Dystrophy have shown to be safe and beneficial. We treated a 20-year-old male suffering from BMD with autologous BMMNC transplantation followed by multidisciplinary rehabilitation. He presented with muscle weakness and had difficulty in performing his activities. The BMMNCs were transplanted via intrathecal and intramuscular routes. The effects were measured on clinical and functional changes. Over 9 months, gradual improvement was noticed in muscle strength, respiratory functions and North Star Ambulatory Assessment Scale. Functional Independence Measure, Berg Balance Score, Brooke and Vignos Scale remained stable indicating halting of the progression. The case report suggests that cellular therapy combined with rehabilitation may have possibility of repairing and regenerating muscle fibers and decreasing the rate of progression of BMD.

  2. Effects of therapeutic exercise on masticatory function in patients with progressive muscular dystrophy.

    OpenAIRE

    Kawazoe, Y; Kobayashi, M; Tasaka, T; Tamamoto, M

    1982-01-01

    The slope of the curve relating integrated electromyographic activity of masseter muscle to biting force, the latency of the jaw-jerk reflex, and masticatory performance wee estimated in patients with Duchenne type of progressive muscular dystrophy before and during therapeutic exercise of the somatogenc system. The slope and latency were slightly decreased, and masticatory performance was increased during exercise. These results suggest that therapeutic exercise of the stomatognathic system ...

  3. Progressive dysphagia in limb-girdle muscular dystrophy type 2B.

    LENUS (Irish Health Repository)

    Walsh, Richard

    2012-02-01

    Dysphagia has not been reported in genetically confirmed limb-girdle muscular dystrophy type 2B (LGMD2B). A 40-year-old woman reported exercise-induced calf pain at age 34, followed by progressive lower and upper limb weakness. At age 38, progressive dysphagia for solids, and subsequently liquids, ensued. Endoscopic and videofluoroscopic-radiological findings indicated a myopathic swallowing disorder. Molecular genetic analysis confirmed two dysferlin gene mutations consistent with a compound heterozygote state. Progressive dysphagia should be considered as part of the expanding dysferlinopathy phenotype.

  4. A case of Fukuyama type congenital muscular dystrophy with progressive changes of brain CT scanning

    International Nuclear Information System (INIS)

    Mori, Kenzi; Saijo, Takahiko; Hamaguchi, Hiroshi; Tayama, Masanobu; Kawano, Noboru; Hashimoto, Toshiaki; Miyao, Masuhide

    1988-01-01

    The Fukuyama type congenital muscular dystrophy (F-CMD) has been generally recognized as a well delineated subgroup of progressive muscular dystrophy with uniform clinical and pathological features. But the pathogenesis is not yet clear. Two theories have been proposed ; autosomal recessive inheritance and intrauterine infection. We experienced a female case of F-CMD, and tried serial brain CT scanning from the birth to one year of age. Low density changes of white matter were not found at the first day of her life. But marked brain atrophy and low density changes of white matter were found after three months. We propose that CT examination should be repeated from early stage to clarify the pathogenesis of F-CMD. (AUTHOR)

  5. Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

    Science.gov (United States)

    Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

    2015-01-01

    Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

  6. Thallium-201 single photon emission computed tomography (SPECT) in patients with Duchenne's progressive muscular dystrophy. A histopathologic correlation study

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Toru; Yanagisawa, Atsuo; Sakata, Konomi; Shimoyama, Katsuya; Yoshino, Hideaki; Ishikawa, Kyozo [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine; Sakata, Hitomi; Ishihara, Tadayuki

    2001-02-01

    The pathomorphologic mechanism responsible for abnormal perfusion imaging during thallium-201 myocardial single photon emission computed tomography ({sup 201}Tl-SPECT) in patients with Duchenne's progressive muscular dystrophy (DMD) was investigated. Hearts from 7 patients with DMD were evaluated histopathologically at autopsy and the results correlated with findings on initial and delayed resting {sup 201}Tl-SPECT images. The location of segments with perfusion defects correlated with the histopathologically abnormal segments in the hearts. Both the extent and degree of myocardial fibrosis were severe, especially in the posterolateral segment of the left ventricle. Severe transmural fibrosis and severe fatty infiltration were common in segments with perfusion defects. In areas of redistribution, the degree of fibrosis appeared to be greater than in areas of normal perfusion; and intermuscular edema was prominent. Thus, the degree and extent of perfusion defects detected by {sup 201}Tl-SPECT were compatible with the histopathology. The presence of the redistribution phenomenon may indicate ongoing fibrosis. Initial and delayed resting {sup 201}Tl-SPECT images can predict the site and progress of myocardial degeneration in patients with DMD. (author)

  7. X linked progressive cone dystrophy. Localisation of the gene locus to Xp21-p11.1 by linkage analysis

    NARCIS (Netherlands)

    Meire, F. M.; Bergen, A. A.; de Rouck, A.; Leys, M.; Delleman, J. W.

    1994-01-01

    Six affected males, three female carriers, and two possible carriers were evaluated from a three generation pedigree with X linked progressive cone dystrophy. The affected males presented with progressive decrease of visual acuity, impairment of colour vision, and deterioration of electroretinogram,

  8. Research progress of motor function assessments and their clinical applications in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Wei SHI

    2015-07-01

    Full Text Available Duchenne muscular dystrophy (DMD, clinically featured as progressive skeletal muscle atrophy with gradual loss of muscle strength and activity abilities, is the most common genetic muscular disease in children throughout the world. The core and continuous characteristic of DMD is motor dysfunction. Motor function assessments of DMD are now focusing on muscle strength, walking ability, range of motion and ability of activities, still without unified standards. Confirming the comprehensive, scientific, reasonable and accurate evaluation tools for DMD assessment is the premise of research in motor developmental rules of DMD, which will help to better understand the motor progress of DMD and to supply evidences for choosing treatment methods, confirming timing of intervention, assessing effect of treatments and designing rehabilitation plans. DOI: 10.3969/j.issn.1672-6731.2015.06.002

  9. Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Kahan, A.; Devaux, J.Y.; Amor, B.

    1986-01-01

    Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined

  10. Myocardial metabolism, perfusion, wall motion and electrical activity in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Perloff, J.K.; Henze, E.; Schelbert, H.R.

    1982-01-01

    The cardiomyopathy of Duchenne's muscular dystrophy originates in the posterobasal left ventricle and extends chiefly to the contiguous lateral wall. Ultrastructural abnormalities in these regions precede connective tissue replacement. We postulated that a metabolic fault coincided with or antedated the subcellular abnormality. Accordingly, regional left ventricular metabolism, perfusion and wall motion were studied using positron computed tomography and metabolic isotopes supplemented by thallium perfusion scans, equilibrium radionuclide angiography and M-mode and two-dimensional echocardiography. To complete the assessment, electrocardiograms, vectorcardiograms, 24 hour taped electrocardiograms and chest x-rays were analyzed. Positron computed tomography utilizing F-18 2-fluoro 2-deoxyglucose (FDG) provided the first conclusive evidence supporting the hypothesis of a premorphologic regional metabolic fault. Thus, cardiac involvement in duchenne dystrophy emerges as a unique form of heart disease, genetically targeting specific regions of ventricular myocardium for initial metabolic and subcellular changes. Reported ultrastructural abnormalities of the impulse and conduction systems provide, at least in part, a basis for the clinically observed sinus node, intraatrial, internodal, AV nodal and infranodal disorders

  11. The progress reports on the development of therapies of Duchenne muscular dystrophy

    Science.gov (United States)

    Scheuerbrandt, G

    2009-01-01

    Summary The roots of the progress reports on the development of therapies for Duchenne muscular dystrophy (DMD) that since 2000 have been produced at Breitnau/Germany and distributed to the parents of DMD patients cover over 30 years of continual occupation with this disease. The beginning was marked by the development of an early detection programme for the genetic disposition for DMD in infant boys. The next step was the organisation of workshops on the management of DMD and the writing of progress reports on these and other relevant conferences. Getting acquainted with the ideas of the protagonists in the research field by holding interviews was a decisive prerequisite for this activity. This took place in tandem with the development of a new kind of multiplex “family letters” that attempted to answer frequently asked questions to many DMD families at the same time. When – with the beginning of the new millennium – the endeavours towards gene therapies for DMD started to boom all over the scientific world, progress reports designed to keep the families informed about research on DMD treatment were added to the family letters. These reports that give an account of the latest state of the research are written in a plain language that can be understood by laypersons. In the meantime the reports have adopted the character of reviews that are updated annually. They are written in English and German and translated into Spanish and many other languages. PMID:20128138

  12. Exoskeletal meal assistance system (EMAS II) for progressive muscle dystrophy patient.

    Science.gov (United States)

    Hasegawa, Yasuhisa; Oura, Saori

    2011-01-01

    This paper introduces a 4-DOFs exoskeletal meal assistance system (EMAS II) for progressive muscle dystrophy patient. It is generally better for the patient to use his/her hands by himself in daily life because active works maintain level of residual functions, health and initiative of him/her. The EMAS II that has a new joystick-type user interface device and three-DOFs on a shoulder part is enhanced for an easier operation and more comfortable support on eating, as the succeeding model of the previous system that has two-DOFs on a shoulder. In order to control the 4-DOFs system by the simple user interface device, the EMAS II simulates upper limb motion patterns of a healthy person. The motion patterns are modeled by extracting correlations between the height of a user's wrist joint and that of the user's elbow joint at the table. Moreover, the EMAS II automatically brings user's hand up to his/her mouth or back to a table when he/she pushes a preset switch on the interface device. Therefore a user has only to control a position of his/her wrist to pick or scoop foods and then flip the switch to start automatic mode, while a height of the elbow joint is automatically controlled by the EMAS II itself. The results of experiments, where a healthy subject regarded as a muscle dystrophy patient eats a meal with EMAS II, show that the subject finished her meal in a natural way in 18 minutes 40 seconds which was within a recommended time of 30 minutes. © 2011 IEEE

  13. Hsp72 preserves muscle function and slows progression of severe muscular dystrophy.

    Science.gov (United States)

    Gehrig, Stefan M; van der Poel, Chris; Sayer, Timothy A; Schertzer, Jonathan D; Henstridge, Darren C; Church, Jarrod E; Lamon, Severine; Russell, Aaron P; Davies, Kay E; Febbraio, Mark A; Lynch, Gordon S

    2012-04-04

    Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca(2+), which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies.

  14. Characteristic of muscle involvement evaluated by CT scans in early stages of progressive muscular dystrophy

    International Nuclear Information System (INIS)

    Arai, Yumi

    1993-01-01

    Muscle CT scans were performed in order to compare the characteristic distribution of progressive muscle involvement in the early stages of Duchenne type (DMD) and Fukuyama type muscular dystrophy (FCMD). Muscle images at the levels of the 3rd lumbar vertebra, thigh and calf were assessed by visual inspection, and mean CT numbers calculated for individual muscles were statistically analysed. On visual inspection, intramuscular low density areas and muscular atrophy were observed in the muscles of older patients with either disease. These changes were, however, more extensive at thigh level in DMD, and at calf level in FCMD. Nevertheless, the mean CT numbers of muscles in which only slight changes were grossly visible on CT scans displayed progressive decreases with increasing age. Moreover, a significant negative relationship was recognizable between age and mean CT number in almost all muscles examined. Comparison of the slopes of the regression lines revealed that the so-called selective pattern of muscle involvement characteristic of the symptomatic stage had already partially manifested in the preclinical or early stages of both diseases. In FCMD, the rates of decrease in CT numbers were extremely rapid for calf muscles as compared with those in DMD, indicating that this is one reason for FCMD patients never becoming ambulatory. However, for almost all of the other muscles, the CT numbers in FCMD decreased in parallel with the corresponding CT numbers in DMD; thus, these diseases displayed a similarity in the pattern of muscle involvement, despite their different pathogenetic mechanisms and inheritance patterns. (author)

  15. Usefulness of BMIPP SPECT to evaluate myocardial viability, contractile reserve and coronary stenotic progression after reperfusion in acute myocardial infarction

    International Nuclear Information System (INIS)

    Katsunuma, Eita; Kurokawa, Shingo; Takahashi, Motoi; Fukuda, Naoto; Kurosawa, Toshiro; Izumi, Tohru

    2001-01-01

    Using combined 123 I-BMIPP (BMIPP), 201 Tl (Tl) and 99m Tc-PYP (PYP) myocardial SPECT imaging, risk areas of acute myocardial infarction were documented in the acute stage, and then these images were evaluated for how well they reflected muscle viability, contractile reserve and coronary stenotic progression subsequent to reperfusion therapy. Patients who only experienced a first attack of myocardial infarction were enrolled. In total, 36 cases who had had the occluded artery successfully reperfused were examined during the past year. They had no significant vessel disease except for the culprit single artery. The patients were comprised of 32 men and 4 women. The mean age was 59.5 years. All patients underwent coronary angiography and left ventricular (LV) angiography in the emergency room. BMIPP/Tl and PYP myocardial SPECT were conducted in the acute stage and chronic stage. In the chronic stage LV angiography was repeated to assess the improvement of LV wall motion. The response to postextrasystolic potentiation (PESP) testing was performed to estimate myocardial contractile reserve. The risk area of acute myocardial infarction (AMI) was documented by reduced BMIPP accumulation. The size of reduced BMIPP accumulation was larger than that of PYP accumulation. A BMIPP/Tl discrepancy and PYP accumulation were documented to assess myocardial viability. Both improvement in LV wall motion and augmentation of PESP response were more closely related to a BMIPP/Tl discrepancy in the presence or absence of PYP accumulation. Therefore, it would be possible to evaluate myocardial viability and contractile reserve by the BMIPP/Tl discrepancy. In patients with good viability, it is important to predict whether there is coronary stenotic progression or not. In this study, we demonstrated that most patients with improved BMIPP images had no significant progression at the site of intervention. Serial observation of BMIPP images from the acute stage to the chronic stage might

  16. Muscle ultrasound quantifies disease progression over time in infants and young boys with duchenne muscular dystrophy.

    Science.gov (United States)

    Zaidman, Craig M; Malkus, Elizabeth C; Connolly, Anne M

    2015-09-01

    Quantitative muscle ultrasound (QUS) in boys with Duchenne muscular dystrophy (DMD) shows increased echointensity as muscle is replaced with fat and fibrosis. Studies of quantitative ultrasound in infants/young boys with DMD over time have not been reported. We used calibrated muscle backscatter (cMB), a reproducible measure of ultrasound echointensity, to quantify muscle pathology in 5 young boys with DMD (ages 0.5-2.8 years) over 17-29 months. We compared the results with repeated assessments of function (n = 4) and with muscle ultrasound images from a cross-section of 6 male controls (0.6-3.1 years). cMB in boys with DMD increased (worsened) over time (P < 0.001), whereas function improved. After age 2 years, cMB in most (4 of 5) boys with DMD was higher than in any control. QUS measures disease progression in young boys with DMD despite functional improvements. QUS could be employed as an outcome measure for serial assessment of young boys with DMD. © 2015 Wiley Periodicals, Inc.

  17. Oral muscles are progressively affected in Duchenne muscular dystrophy: implications for dysphagia treatment.

    Science.gov (United States)

    van den Engel-Hoek, Lenie; Erasmus, Corrie E; Hendriks, Jan C M; Geurts, Alexander C H; Klein, Willemijn M; Pillen, Sigrid; Sie, Lilian T; de Swart, Bert J M; de Groot, Imelda J M

    2013-05-01

    Dysphagia is reported in advanced stages of Duchenne muscular dystrophy (DMD). The population of DMD is changing due to an increasing survival. We aimed to describe the dysphagia in consecutive stages and to assess the underlying mechanisms of dysphagia in DMD, in order to develop mechanism based recommendations for safe swallowing. In this cross-sectional study, participants were divided into: early and late ambulatory stage (AS, n = 6), early non-ambulatory stage (ENAS, n = 7), and late non-ambulatory stage (LNAS, n = 11). Quantitative oral muscle ultrasound was performed to quantify echo intensity. Swallowing was assessed with a video fluoroscopic swallow study, surface electromyography (sEMG) of the submental muscle group and tongue pressure. Differences in outcome parameters among the three DMD stages were tested with analysis of variance. Oral muscles related to swallowing were progressively affected, starting in the AS with the geniohyoid muscle. Tongue (pseudo) hypertrophy was found in 70 % of patients in the ENAS and LNAS. Oral phase problems and post-swallow residue were observed, mostly in the LNAS with solid food. sEMG and tongue pressure data of swallowing solid food revealed the lowest sEMG amplitude, the longest duration and lowest tongue pressure in the LNAS. In case of swallowing problems in DMD, based on the disturbed mechanisms of swallowing, it is suggested to (1) adjust meals in terms of less solid food, and (2) drink water after meals to clear the oropharyngeal area.

  18. Progression and variation of fatty infiltration of the thigh muscles in Duchenne muscular dystrophy, a muscle magnetic resonance imaging study.

    Science.gov (United States)

    Li, Wenzhu; Zheng, Yiming; Zhang, Wei; Wang, Zhaoxia; Xiao, Jiangxi; Yuan, Yun

    2015-05-01

    The purpose of this study was to assess the progression and variation of fatty infiltration of the thigh muscles of Duchenne muscular dystrophy patients. Muscle magnetic resonance imaging was used to measure the degree of fatty infiltration of the thigh muscles of 171 boys with Duchenne muscular dystrophy (mean age, 6.09 ± 2.30 years). Fatty infiltration was assigned using a modified Mercuri's scale 0-5 (normal-severe). The gluteus maximus and adductor magnus were affected in patients less than two years old, followed by the biceps femoris. Quadriceps and semimembranosus were first affected at the age of five to six years; the sartorius, gracilis and adductor longus remained apparently unaffected until seven years of age. Fatty infiltration of all the thigh muscles developed rapidly after seven years of age. The standard deviation of the fatty infiltration scores ranged from 2.41 to 4.87 before five years old, and from 6.84 to 11.66 between six and ten years old. This study provides evidence of highly variable degrees of fatty infiltration in children of different ages with Duchenne muscular dystrophy, and indicates that fatty infiltration progresses more quickly after seven years of age. These findings may be beneficial for the selection of therapeutic regimens and the analysis of future clinical trials. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. The relationship between clinical stage, prognosis and myocardial damage in patients with Duchenne-type muscular dystrophy. Five-year follow-up study

    International Nuclear Information System (INIS)

    Naruse, Hitoshi; Miyagi, Junko; Arii, Tohru; Ohyanagi, Mitsumasa; Iwasaki, Tadaaki; Jinnai, Kenji

    2004-01-01

    The evaluation of myocardial damage by [ 123 I]15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) imaging, which represents free fatty acid metabolism, has not been reported in patients with Duchenne-type muscular dystrophy (DMD). To date, the relationship between clinical stage, prognosis and myocardial damage has not been evaluated by radionuclear cardiac imaging. The main goal of this study was to elucidate the relationship of quantitative indices of myocardial damage obtained by radionuclear cardiac imaging ([ 201 Tl] and [ 123 I]BMIPP) to clinical stage and incidence of severe cardiac events in patients with Duchenne-type muscular dystrophy (DMD). The study population consisted of 28 male patients with DMD. The average age at the beginning of observation was 19.1±7.4 yrs. Nuclear tomographic imaging was performed using [ 201 Tl] and [ 123 I]BMIPP. The mid-ventricular short axial slices were classified into four anatomical regions, and the normalized count data in these areas (TL, BM) were obtained. The endpoint was the occurrence of heart failure during the follow up period. Thirteen cases of heart failure occurred during the 5-year follow-up period, including three cases with cardiac death due to congestive heart failure. Clinical staging correlated directly with TL (p=0.0118) and BM (p=0.0401) in the whole left ventricle. In regional TL analysis, an association was observed only in the septum (p=0.0151), and in the anterior (p=0.0361) region. The only discrepancy between the tracer parameters (TL-BM) in the septum was observed with the radionuclear cardiac values, which exhibited a relationship with cardiac events (p=0.0124). This discordance, TL 201 Tl] in this area was representative of the clinical stage, and TL-BM correlated well with the prognosis. (author)

  20. A study of atriphos (ATP) action on muscular circulation in progressive muscular dystrophy by the radioactive xenon clearance technique

    International Nuclear Information System (INIS)

    Chakyrov, B.; Samardzhiev, A.

    1977-01-01

    The effect of intramuscularly and intravenously adminostered atriphos on the muscular circulation was studied with radioactive xenon in 12 children with progressive muscular dystrophy. After combined local intramuscular injection of ATP (atriphos) with the radioactive marker a 12-fold increment of muscular circulation ensues, lasting about 15 minutes. No vasodilatating effect on the muscular flow was oberved after intravenous injection of 20-40 mg of atriphos. It is believed that intramuscular administration of atriphos produced dilatation of capillaries and of the venous part of the muscular circulation. (author)

  1. Early Detection of Myocardial Bioenergetic Deficits: A 9.4 Tesla Complete Non Invasive 31P MR Spectroscopy Study in Mice with Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Weina Cui

    Full Text Available Duchenne muscular dystrophy (DMD is the most common fatal form of muscular dystrophy characterized by striated muscle wasting and dysfunction. Patients with DMD have a very high incidence of heart failure, which is increasingly the cause of death in DMD patients. We hypothesize that in the in vivo system, the dystrophic cardiac muscle displays bioenergetic deficits prior to any functional or structural deficits. To address this we developed a complete non invasive 31P magnetic resonance spectroscopy (31P MRS approach to measure myocardial bioenergetics in the heart in vivo.Six control and nine mdx mice at 5 months of age were used for the study. A standard 3D -Image Selected In vivo Spectroscopy (3D-ISIS sequence was used to provide complete gradient controlled three-dimensional localization for heart 31P MRS. These studies demonstrated dystrophic hearts have a significant reduction in PCr/ATP ratio compare to normal (1.59±0.13 vs 2.37±0.25, p<0.05.Our present study provides the direct evidence of significant cardiac bioenergetic deficits in the in vivo dystrophic mouse. These data suggest that energetic defects precede the development of significant hemodynamic or structural changes. The methods provide a clinically relevant approach to use myocardial energetics as an early marker of disease in the dystrophic heart. The new method in detecting the in vivo bioenergetics abnormality as an early non-invasive marker of emerging dystrophic cardiomyopathy is critical in management of patients with DMD, and optimized therapies aimed at slowing or reversing the cardiomyopathy.

  2. Oral muscles are progressively affected in Duchenne muscular dystrophy : Implications for dysphagia treatment

    NARCIS (Netherlands)

    Bert de Swart; W. Klein; L. van den Engel-Hoek; S. Pillen; J. Hendriks; Alexander Geurts; I. de Groot; L. Sie; C. Erasmus

    2012-01-01

    Dysphagia is reported in advanced stages of Duchenne muscular dystrophy (DMD). The population of DMD is changing due to an increasing survival. We aimed to describe the dysphagia in consecutive stages and to assess the underlying mechanisms of dysphagia in DMD, in order to develop mechanism based

  3. Oral muscles are progressively affected in Duchenne muscular dystrophy: implications for dysphagia treatment

    NARCIS (Netherlands)

    Engel-Hoek, L. van den; Erasmus, C.E.; Hendriks, J.C.M.; Geurts, A.C.H.; Klein, W.M.; Pillen, S.; Sie, L.T.L.; Swart, B.J.M. de; Groot, I.J.M. de

    2013-01-01

    Dysphagia is reported in advanced stages of Duchenne muscular dystrophy (DMD). The population of DMD is changing due to an increasing survival. We aimed to describe the dysphagia in consecutive stages and to assess the underlying mechanisms of dysphagia in DMD, in order to develop mechanism based

  4. Inflammatory monocytes promote progression of Duchenne muscular dystrophy and can be therapeutically targeted via CCR2

    OpenAIRE

    Mojumdar, Kamalika; Liang, Feng; Giordano, Christian; Lemaire, Christian; Danialou, Gawiyou; Okazaki, Tatsuma; Bourdon, Johanne; Rafei, Moutih; Galipeau, Jacques; Divangahi, Maziar; Petrof, Basil J

    2014-01-01

    Myofiber necrosis and fibrosis are hallmarks of Duchenne muscular dystrophy (DMD), leading to lethal weakness of the diaphragm. Macrophages (MPs) are required for successful muscle regeneration, but the role of inflammatory monocyte (MO)-derived MPs in either promoting or mitigating DMD is unclear. We show that DMD (mdx) mouse diaphragms exhibit greatly increased expression of CCR2 and its chemokine ligands, along with inflammatory (Ly6Chigh) MO recruitment and accumulation of CD11bhigh MO-de...

  5. CT evaluation of the damaged upper limb muscle in patients with Duchenne type progressive muscular dystrophy (DMD)

    International Nuclear Information System (INIS)

    Saito, Hiroshi; Matsuke, Yutaka.

    1992-01-01

    In order to evaluate the changes of CT numbers and cross sectional areas of the muscles, we determined CT scores of the muscle. In twelve patients with Duchenne type progressive muscular dystrophy (DMD), we assessed the difference of CT scores of the muscle and the correlation between CT score of the muscle and 9-stage classification of upper extremities. CT scores of the subscapularis muscle and infraspinatus muscle were significantly lower than deltoideus muscle at the level of the shoulder, and flexor muscles showed also significantly lower than extensor muscles at the level of the upper extremity. Good correlations between CT score of the muscle and 9-stage classification of upper extremities were observed in the muscles of shoulder and upper arm. (author)

  6. CT evaluation of the damaged upper limb muscle in patients with Duchenne type progressive muscular dystrophy (DMD)

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Hiroshi (Anan Central Hospital, Tokushima (Japan)); Matsuke, Yutaka

    1992-04-01

    In order to evaluate the changes of CT numbers and cross sectional areas of the muscles, we determined CT scores of the muscle. In twelve patients with Duchenne type progressive muscular dystrophy (DMD), we assessed the difference of CT scores of the muscle and the correlation between CT score of the muscle and 9-stage classification of upper extremities. CT scores of the subscapularis muscle and infraspinatus muscle were significantly lower than deltoideus muscle at the level of the shoulder, and flexor muscles showed also significantly lower than extensor muscles at the level of the upper extremity. Good correlations between CT score of the muscle and 9-stage classification of upper extremities were observed in the muscles of shoulder and upper arm. (author).

  7. The effect of progressive muscle relaxation techniques on anxiety in Patients with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Mozhgan Jariani

    2011-12-01

    Conclusion: progressive muscle relaxation can reduce the amount of anxiety, and systolic and diastolic blood pressure of the patients with myocardial infarction hospitalized in CCU ward, therefore it can play an effective role as a supplement non-medicinal, simple and cheap treatment for these patients

  8. Progress on gene therapy, cell therapy, and pharmacological strategies toward the treatment of oculopharyngeal muscular dystrophy.

    Science.gov (United States)

    Harish, Pradeep; Malerba, Alberto; Dickson, George; Bachtarzi, Houria

    2015-05-01

    Oculopharyngeal muscular dystrophy (OPMD) is a muscle-specific, late-onset degenerative disorder whereby muscles of the eyes (causing ptosis), throat (leading to dysphagia), and limbs (causing proximal limb weakness) are mostly affected. The disease is characterized by a mutation in the poly(A)-binding protein nuclear-1 (PABPN1) gene, resulting in a short GCG expansion in the polyalanine tract of PABPN1 protein. Accumulation of filamentous intranuclear inclusions in affected skeletal muscle cells constitutes the pathological hallmark of OPMD. This review highlights the current translational research advances in the treatment of OPMD. In vitro and in vivo disease models are described. Conventional and experimental therapeutic approaches are discussed with emphasis on novel molecular therapies including the use of intrabodies, gene therapy, and myoblast transfer therapy.

  9. Distrofia oftalmoplégica progressiva. Forma de inicio ocular precoce e comprometimento muscular universal tardio Progressive ophthalmoplegic dystrophy

    Directory of Open Access Journals (Sweden)

    João P. Rodrigues

    1968-03-01

    Full Text Available É estudada uma forma particular de distrofia muscular progressiva — forma óculo-faríngea — cujo diagnóstico foi comprovado mediante traçados eletromiográficos e biópsia do músculo orbicular da pálpebra. São analisadas as duas formas de distrofias oftalmoplégicas: 1 miopatia ocular; 2 miopatia óculo-faríngea. A forma óculo-faríngea é mais rara, incide em idades mais avançadas (média de 40 anos em comparação com a forma ocular pura (média de 23 anos; além disso, é ressaltada a alta incidência familiar daquela forma de miopatia. O caso ora registrado parece ser um élo entre as duas formas, pois o início foi precoce, sem incidência familiar e com comprometimento da deglutição e de músculos da face, pescoço, tronco, cintura escapular, pélvica e dos membros.A case of peculiar form of progressive muscular dystrophy — the oculopharyngeal one — is reported. The diagnosis was ascertained by electromiography and biopsy of orbicularis palpebrae muscle. Two forms of ophthalmoplegic dystrophy are analysed: 1 ocular myopathy and 2 oculopharyngeal miopathy. The latter is less frequent, occurring on patients in the fourth decade, in comparison with the pure ocular form affecting patients in the second decade. Besides this, the high familial incidence of the oculo-pharyngeal form is stressed. The reported case seems to be an intermediate form between them. The onset occurred at 11 years of age; there was no other case in the family, the disease involving swallowing, face, neck, trunk, shoulder, pelvic and members muscles.

  10. Tratamento da distrofia muscular progressiva com lactato de sódio Treatment of progressive muscular dystrophy with sodium lactate

    Directory of Open Access Journals (Sweden)

    José Antonio Levy

    1969-12-01

    Full Text Available Com base em trabalhos anteriores, 13 casos de distrofia muscular progressiva foram tratados com lactato de sódio 1/6 molar associado a ATP e complexo B. O exame da força muscular, realizado antes e após o tratamento — salvo em dois casos nos quais ocorreram melhoras muito discretas — não mostrou qualquer efeito favorável da medicação. Os autores sugerem a verificação de possíveis alterações enzimáticas provocadas pelo lactato de sódio, o que serviria para melhor avaliação do efeito terapêutico.Thirteen cases of progressive muscular dystrophy were treated with 1/6 M. sodium lactate plus ATP and B complex. Examinations of muscle strength, before and after the treatment, did not show any favourable effects, except in two of the cases which showed slight improvement. The authors suggest that possible enzimatic alterations caused by the sodium lactate be checked up on, since this checking could be employed in the evaluation of the therapeutic effects.

  11. The heart in Becker muscular dystrophy, facioscapulohumeral dystrophy, and Bethlem myopathy

    NARCIS (Netherlands)

    de Visser, M.; de Voogt, W. G.; la Rivière, G. V.

    1992-01-01

    We report a study, assessing involvement of the heart in 33 familial cases of Becker muscular dystrophy (BMD), 31 familiar cases of facioscapulohumeral (FSH) dystrophy, and 27 familial cases of Bethlem myopathy. In the patients with BMD, correlations of myocardial involvement with age and extent of

  12. The Clinical Observation on one case of Patient with Progressive Muscular Dystrophies

    Directory of Open Access Journals (Sweden)

    Yoo, Chang-Kil

    2000-12-01

    Full Text Available After observing a patient diagnosed with Progressive Muscular Dystropies from the August, 31, 2000 to the January, 2001, the following results are obtained. Method and Result: Under our assumption that the Korean Bee Venom Therapy is a good method to treat Progress Muscular Dystropies. Korean Bee Venom Therapy was applied on the following acupuncture points: BL23(Shinsu:腎兪, BL26(Guanyuanshu:關元兪, ST36(Chok-Samni:足三里, LI4(Hapkok:合谷, LV3(Taechung:太, SP10(Hyolhae:血海, SI9(Sojang-Kyonjong:貞. In addition CFC(Carthami Flos;紅花: and Cervi Pantotrichum Cornu; Herbal-Acupuncture is also treated on the other acupuncture points. For herbal medication was given to the patient based on the Sasang Constitution, Taeyangin Ogapijangchuk-tang. Following these treatments in this case of Progressive Muscular Dystropies, the skeletal muscle functions made remarkable improvement. Conclusion: Based on the clinical results, traditional Korean Medical treatment is believed to be effective for treating Progressive Muscular Dystropies, and further studies should be conducted to provide more valuable information.

  13. Occult Macular Dystrophy

    Directory of Open Access Journals (Sweden)

    Işıl Sayman Muslubaş

    2016-04-01

    Full Text Available Occult macular dystrophy is an inherited macular dystrophy characterized by a progressive decline of bilateral visual acuity with normal fundus appearance, fluorescein angiogram and full-field electroretinogram. This case report presents a 20-year-old female patient with bilateral progressive decline of visual acuity for six years. Her visual acuity was 3-4/10 in both eyes. Anterior segment and fundus examination, fluorescein angiogram and full-field electroretinogram were normal. She could read all Ishihara pseudoisochromatic plates. Fundus autofluorescence imaging was normal. There was a mild central hyporeflectance on fundus infrared reflectance imaging in both eyes. Reduced foveal thickness and alterations of the photoreceptor inner and outer segment junction were observed by optical coherence tomography in both eyes. Central scotoma was also found by microperimetry and reduced central response was revealed by multifocal electroretinogram in both eyes. These findings are consistent with the clinical characteristics of occult macular dystrophy

  14. Early-progressive dilated cardiomyopathy in a family with Becker muscular dystrophy related to a novel frameshift mutation in the dystrophin gene exon 27.

    Science.gov (United States)

    Tsuda, Takeshi; Fitzgerald, Kristi; Scavena, Mena; Gidding, Samuel; Cox, Mary O; Marks, Harold; Flanigan, Kevin M; Moore, Steven A

    2015-03-01

    We report a family in which two male siblings with Becker muscular dystrophy (BMD) developed severe dilated cardiomyopathy (DCM) and progressive heart failure (HF) at age 11 years; one died at age 14 years while awaiting heart transplant and the other underwent left ventricular assist device implantation at the same age. Genetic analysis of one sibling showed a novel frameshift mutation in exon 27 of Duchenne muscular dystrophy (DMD) gene (c.3779_3785delCTTTGGAinsGG), in which seven base pairs are deleted and two are inserted. Although this predicts an amino-acid substitution and premature termination (p.Thr1260Argfs*8), muscle biopsy dystrophin immunostaining instead indicates that the mutation is more likely to alter splicing. Despite relatively preserved skeletal muscular performance, both the siblings developed progressive HF secondary to early-onset DCM. In addition, their 7-year-old nephew with delayed gross motor development, mild proximal muscle weakness and markedly elevated serum creatine kinase level (>13 000 IU l(-1)) at 16 months was recently demonstrated to have the familial DMD mutation. Here, we report a novel genotype of BMD with early-onset DCM and progressive lethal HF during early adolescence.

  15. Myotonic Muscular Dystrophy

    Science.gov (United States)

    ... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

  16. Superpulsed low-level laser therapy protects skeletal muscle of mdx mice against damage, inflammation and morphological changes delaying dystrophy progression.

    Science.gov (United States)

    Leal-Junior, Ernesto Cesar Pinto; de Almeida, Patrícia; Tomazoni, Shaiane Silva; de Carvalho, Paulo de Tarso Camillo; Lopes-Martins, Rodrigo Álvaro Brandão; Frigo, Lucio; Joensen, Jon; Johnson, Mark I; Bjordal, Jan Magnus

    2014-01-01

    To evaluate the effects of preventive treatment with low-level laser therapy (LLLT) on progression of dystrophy in mdx mice. Ten animals were randomly divided into 2 experimental groups treated with superpulsed LLLT (904 nm, 15 mW, 700 Hz, 1 J) or placebo-LLLT at one point overlying the tibialis anterior muscle (bilaterally) 5 times per week for 14 weeks (from 6th to 20th week of age). Morphological changes, creatine kinase (CK) activity and mRNA gene expression were assessed in animals at 20th week of age. Animals treated with LLLT showed very few morphological changes in skeletal muscle, with less atrophy and fibrosis than animals treated with placebo-LLLT. CK was significantly lower (p=0.0203) in animals treated with LLLT (864.70 U.l-1, SEM 226.10) than placebo (1708.00 U.l-1, SEM 184.60). mRNA gene expression of inflammatory markers was significantly decreased by treatment with LLLT (pmuscle damage and inflammation in mdx mice. This indicates that LLLT has potential to decrease progression of Duchenne muscular dystrophy.

  17. Muscular Dystrophy

    Science.gov (United States)

    ... Surveillance Tracking and Research Network , known as MD STAR net . Learn more about CDC’s other muscular dystrophy ... for Disease Control and Prevention Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

  18. Muscular dystrophy

    Science.gov (United States)

    ... are no known cures for the various muscular dystrophies. The goal of treatment is to control symptoms. Physical therapy may help maintain muscle strength and function. Leg braces and a wheelchair ...

  19. Computerized tomography in myotonic dystrophy

    International Nuclear Information System (INIS)

    Gellerich, I.; Mueller, D.; Koch, R.D.

    1986-01-01

    Besides clinical symptoms, progress and electromyography computerized tomography improves the diagnostics of myotonic dystrophy. Even small changes in muscular structure are detectable and especially the musculus soleus exhibits early and pronounced alterations. By means of density distribution pattern an improved characterization of the disease is possible. Additional information is obtained by cerebral computerized tomography. Atrophy of brain tissue is to be expected in all patients with myotonic dystrophy. (author)

  20. Muscular Dystrophy

    Science.gov (United States)

    ... sets of muscles and cause different degrees of muscle weakness. Duchenne muscular dystrophy is the most common and the most severe ... can walk independently. Prednisone If a child has Duchenne muscular ... to help slow the rate of muscle deterioration. By doing so, the child may be ...

  1. A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging

    DEFF Research Database (Denmark)

    Anvar, Seyed Yahya; Raz, Yotam; Verway, Nisha

    2013-01-01

    Oculopharyngeal muscular dystrophy (OPMD) is caused by trinucleotide repeat expansion mutations in Poly(A) binding protein 1 (PABPN1). PABPN1 is a regulator of mRNA stability and is ubiquitously expressed. Here we investigated how symptoms in OPMD initiate only at midlife and why a subset...... of skeletal muscles is predominantly affected. Genome-wide RNA expression profiles from Vastus lateralis muscles human carriers of expanded-PABPN1 at pre-symptomatic and symptomatic stages were compared with healthy controls. Major expression changes were found to be associated with age rather than...... with expression of expanded-PABPN1, instead transcriptomes of OPMD and elderly muscles were significantly similar (P...

  2. Hereditary muscular dystrophies and the heart

    NARCIS (Netherlands)

    Hermans, M. C. E.; Pinto, Y. M.; Merkies, I. S. J.; de Die-Smulders, C. E. M.; Crijns, H. J. G. M.; Faber, C. G.

    2010-01-01

    Cardiac disease is a common clinical manifestation of neuromuscular disorders, particularly of muscular dystrophies. Heart muscle cells as well as specialized conducting myocardial fibres may be affected by the dystrophic process. The incidence and nature of cardiac involvement vary with different

  3. Myocardial infarction increases progressive visual field defects in well treated early primary open angle glaucoma--a prospective case control study.

    Science.gov (United States)

    Mondal, Lakshmikanta; Baidya, Krishnapada; Choudhury, Himadri; Roy, Rupam

    2013-06-01

    The purpose of the study was to evaluate the progression of glaucomatous field damage in patients with stable primary open angle glaucoma after an attack of myocardial infarction. In this case control study, 62 open angle glaucoma patients were selected and regularly followed up. Among 62 patients, 9 had an attack of myocardial infarction. The intra-ocular pressure and visual field progression of both the groups (myocardial infarction versus no myocardial infarction) were analysed. Three (33.3%) out of 9 patients who had suffered from myocardial infarction showed progressive visual field loss whereas only 9 (16.9%) out of 53 patients who did not suffer from myocardial infarction, showed progressive field changes. Both the groups had stable target intra-ocular pressure between 14 and 16 mm Hg. Myocardial infarction may adversely influence the progression of primary open angle glaucoma which is suspected to result from ischaemia induced neuronal loss and only control of intraocular pressure is not the only solution. We have to look for other drugs that prevents ischaemia induced neuronal damage.

  4. Changes in calsequestrin, TNF-α, TGF-β and MyoD levels during the progression of skeletal muscle dystrophy in mdx mice: a comparative analysis of the quadriceps, diaphragm and intrinsic laryngeal muscles.

    Science.gov (United States)

    Barros Maranhão, Juliana; de Oliveira Moreira, Drielen; Maurício, Adriana Fogagnolo; de Carvalho, Samara Camaçari; Ferretti, Renato; Pereira, Juliano Alves; Santo Neto, Humberto; Marques, Maria Julia

    2015-10-01

    In Duchenne muscular dystrophy (DMD), the search for new biomarkers to follow the evolution of the disease is of fundamental importance in the light of the evolving gene and pharmacological therapies. In addition to the lack of dystrophin, secondary events including changes in calcium levels, inflammation and fibrosis greatly contribute to DMD progression and the molecules involved in these events may represent potential biomarkers. In this study, we performed a comparative evaluation of the progression of dystrophy within muscles that are differently affected by dystrophy (diaphragm; DIA and quadriceps; QDR) or spared (intrinsic laryngeal muscles) using the mdx mice model of DMD. We assessed muscle levels of calsequestrin (calcium-related protein), tumour necrosis factor (TNF-α; pro-inflammatory cytokine), tumour growth factor (TGF-β; pro-fibrotic factor) and MyoD (muscle proliferation) vs. histopathology at early (1 and 4 months of age) and late (9 months of age) stages of dystrophy. Fibrosis was the primary feature in the DIA of mdx mice (9 months: 32% fibrosis), which was greater than in the QDR (9 months: 0.6% fibrosis). Muscle regeneration was the primary feature in the QDR (9 months: 90% of centrally nucleated fibres areas vs. 33% in the DIA). The QDR expressed higher levels of calsequestrin than the DIA. Laryngeal muscles showed normal levels of TNF-α, TGF-β and MyoD. A positive correlation between histopathology and cytokine levels was observed only in the diaphragm, suggesting that TNF-α and TGF-β serve as markers of dystrophy primarily for the diaphragm. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

  5. Characteristic of muscle involvement evaluated by CT scans in early stages of progressive muscular dystrophy; Comparison between Duchenne and Fukuyama types

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Yumi (Tokyo Women' s Medical Coll. (Japan))

    1993-10-01

    Muscle CT scans were performed in order to compare the characteristic distribution of progressive muscle involvement in the early stages of Duchenne type (DMD) and Fukuyama type muscular dystrophy (FCMD). Muscle images at the levels of the 3rd lumbar vertebra, thigh and calf were assessed by visual inspection, and mean CT numbers calculated for individual muscles were statistically analysed. On visual inspection, intramuscular low density areas and muscular atrophy were observed in the muscles of older patients with either disease. These changes were, however, more extensive at thigh level in DMD, and at calf level in FCMD. Nevertheless, the mean CT numbers of muscles in which only slight changes were grossly visible on CT scans displayed progressive decreases with increasing age. Moreover, a significant negative relationship was recognizable between age and mean CT number in almost all muscles examined. Comparison of the slopes of the regression lines revealed that the so-called selective pattern of muscle involvement characteristic of the symptomatic stage had already partially manifested in the preclinical or early stages of both diseases. In FCMD, the rates of decrease in CT numbers were extremely rapid for calf muscles as compared with those in DMD, indicating that this is one reason for FCMD patients never becoming ambulatory. However, for almost all of the other muscles, the CT numbers in FCMD decreased in parallel with the corresponding CT numbers in DMD; thus, these diseases displayed a similarity in the pattern of muscle involvement, despite their different pathogenetic mechanisms and inheritance patterns. (author).

  6. An unusual variant of Becker muscular dystrophy

    NARCIS (Netherlands)

    de Visser, M.; Bakker, E.; Defesche, J. C.; Bolhuis, P. A.; van Ommen, G. J.

    1990-01-01

    We report on 5 brothers with slowly progressive limbgirdle weakness. Calf hypertrophy was absent. The levels of creatine kinase, electromyography, and findings from a muscle biopsy specimen were compatible with muscular dystrophy. The propositus's biopsy specimen also showed numerous rimmed

  7. Myocardial Bridging

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2016-02-01

    Full Text Available Abstract Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results.

  8. Muscular dystrophy in a dog resembling human becker muscular dystrophy.

    Science.gov (United States)

    Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

    2014-05-01

    A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Progression of spinal deformity in wheelchair-dependent patients with Duchenne muscular dystrophy who are not treated with steroids: coronal plane (scoliosis) and sagittal plane (kyphosis, lordosis) deformity.

    Science.gov (United States)

    Shapiro, F; Zurakowski, D; Bui, T; Darras, B T

    2014-01-01

    We determined the frequency, rate and extent of development of scoliosis (coronal plane deformity) in wheelchair-dependent patients with Duchenne muscular dystrophy (DMD) who were not receiving steroid treatment. We also assessed kyphosis and lordosis (sagittal plane deformity). The extent of scoliosis was assessed on sitting anteroposterior (AP) spinal radiographs in 88 consecutive non-ambulatory patients with DMD. Radiographs were studied from the time the patients became wheelchair-dependent until the time of spinal fusion, or the latest assessment if surgery was not undertaken. Progression was estimated using a longitudinal mixed-model regression analysis to handle repeated measurements. Scoliosis ≥ 10° occurred in 85 of 88 patients (97%), ≥ 20° in 78 of 88 (89%) and ≥ 30° in 66 of 88 patients (75%). The fitted longitudinal model revealed that time in a wheelchair was a highly significant predictor of the magnitude of the curve, independent of the age of the patient (p lordosis (16 (27%) abnormal and seven (11%) normal). This study provides a baseline to assess the effects of steroids and other forms of treatment on the natural history of scoliosis in patients with DMD, and an approach to assessing spinal deformity in the coronal and sagittal planes in wheelchair-dependent patients with other neuromuscular disorders.

  10. Early myocardial damage assessment in dystrophinopathies using 99Tcm-MIBI gated myocardial perfusion imaging

    Directory of Open Access Journals (Sweden)

    Zhang L

    2015-12-01

    Full Text Available Li Zhang,1,* Zhe Liu,2,* Ke-You Hu,3 Qing-Bao Tian,3 Ling-Ge Wei,4 Zhe Zhao,5 Hong-Rui Shen,5 Jing Hu5 1Department of Cardiovascular Disorders, 2Department of Geriatrics, The Third Hospital of Hebei Medical University, 3The Public Health Department, Hebei Medical University, 4Department of Nuclear Medicine, 5Department of Neuromuscular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China *Li Zhang and Zhe Liu are first coauthors of this paper Background: Early detection of muscular dystrophy (MD-associated cardiomyopathy is important because early medical treatment may slow cardiac remodeling and attenuate symptoms of cardiac dysfunction; however, no sensitive and standard diagnostic method for MD at an earlier stage has been well-recognized. Thus, the aim of this study was to test the early diagnostic value of technetium 99m-methoxyisobutylisonitrile (99Tcm-MIBI gated myocardial perfusion imaging (G-MPI for MD.Methods and results: Ninety-one patients underwent 99Tcm-MIBI G-MPI examinations when they were diagnosed with Duchenne muscular dystrophy (DMD (n=77 or Becker muscular dystrophy (BMD; n=14. 99Tcm-MIBI G-MPI examinations were repeated in 43 DMD patients who received steroid treatments for 2 years as a follow-up examination. Myocardial defects were observed in nearly every segment of the left ventricular wall in both DMD and BMD patients compared with controls, especially in the inferior walls and the apices by using 99Tcm-MIBI G-MPI. Cardiac wall movement impairment significantly correlated with age in the DMD and BMD groups (rs=0.534 [P<0.05] and rs=0.784 [P<0.05], respectively. Intermittent intravenous doses of glucocorticoids and continuation with oral steroid treatments significantly improved myocardial function in DMD patients (P<0.05, but not in BMD patients.Conclusion: 99Tcm-MIBI G-MPI is a sensitive and safe approach for early evaluation of cardiomyopathy in patients with DMD or BMD

  11. Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy.

    Science.gov (United States)

    Zanotti, Simona; Gibertini, Sara; Curcio, Maurizio; Savadori, Paolo; Pasanisi, Barbara; Morandi, Lucia; Cornelio, Ferdinando; Mantegazza, Renato; Mora, Marina

    2015-07-01

    Excessive extracellular matrix deposition progressively replacing muscle fibres is the endpoint of most severe muscle diseases. Recent data indicate major involvement of microRNAs in regulating pro- and anti-fibrotic genes. To investigate the roles of miR-21 and miR-29 in muscle fibrosis in Duchenne muscle dystrophy, we evaluated their expression in muscle biopsies from 14 patients, and in muscle-derived fibroblasts and myoblasts. In Duchenne muscle biopsies, miR-21 expression was significantly increased, and correlated directly with COL1A1 and COL6A1 transcript levels. MiR-21 expression was also significantly increased in Duchenne fibroblasts, more so after TGF-β1 treatment. In Duchenne fibroblasts the expression of miR-21 target transcripts PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SPRY-1 (Sprouty homolog 1) was significantly reduced; while collagen I and VI transcript levels and soluble collagen production were significantly increased. MiR-29a and miR-29c were significantly reduced in Duchenne muscle and myoblasts, and miR-29 target transcripts, COL3A1, FBN1 and YY1, significantly increased. MiR-21 silencing in mdx mice reduced fibrosis in the diaphragm muscle and in both Duchenne fibroblasts and mdx mice restored PTEN and SPRY-1 expression, and significantly reduced collagen I and VI expression; while miR-29 mimicking in Duchenne myoblasts significantly decreased miR-29 target transcripts. These findings indicate that miR-21 and miR-29 play opposing roles in Duchenne muscle fibrosis and suggest that pharmacological modulation of their expression has therapeutic potential for reducing fibrosis in this condition. Copyright © 2015. Published by Elsevier B.V.

  12. SU9516 Increases α7β1 Integrin and Ameliorates Disease Progression in the mdx Mouse Model of Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Sarathy, Apurva; Wuebbles, Ryan D; Fontelonga, Tatiana M; Tarchione, Ashley R; Mathews Griner, Lesley A; Heredia, Dante J; Nunes, Andreia M; Duan, Suzann; Brewer, Paul D; Van Ry, Tyler; Hennig, Grant W; Gould, Thomas W; Dulcey, Andrés E; Wang, Amy; Xu, Xin; Chen, Catherine Z; Hu, Xin; Zheng, Wei; Southall, Noel; Ferrer, Marc; Marugan, Juan; Burkin, Dean J

    2017-06-07

    Duchenne muscular dystrophy (DMD) is a fatal muscle disease caused by mutations in the dystrophin gene, resulting in a complete loss of the dystrophin protein. Dystrophin is a critical component of the dystrophin glycoprotein complex (DGC), which links laminin in the extracellular matrix to the actin cytoskeleton within myofibers and provides resistance to shear stresses during muscle activity. Loss of dystrophin in DMD patients results in a fragile sarcolemma prone to contraction-induced muscle damage. The α7β1 integrin is a laminin receptor protein complex in skeletal and cardiac muscle and a major modifier of disease progression in DMD. In a muscle cell-based screen for α7 integrin transcriptional enhancers, we identified a small molecule, SU9516, that promoted increased α7β1 integrin expression. Here we show that SU9516 leads to increased α7B integrin in murine C2C12 and human DMD patient myogenic cell lines. Oral administration of SU9516 in the mdx mouse model of DMD increased α7β1 integrin in skeletal muscle, ameliorated pathology, and improved muscle function. We show that these improvements are mediated through SU9516 inhibitory actions on the p65-NF-κB pro-inflammatory and Ste20-related proline alanine rich kinase (SPAK)/OSR1 signaling pathways. This study identifies a first in-class α7 integrin-enhancing small-molecule compound with potential for the treatment of DMD. Copyright © 2017 The American Society of Gene and Cell Therapy. All rights reserved.

  13. Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Banihani, Rudaina; Smile, Sharon; Yoon, Grace; Dupuis, Annie; Mosleh, Maureen; Snider, Andrea; McAdam, Laura

    2015-10-01

    Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of Duchenne muscular dystrophy. © The Author(s) 2015.

  14. The progress of research on myocardial perfusion imaging in diabetic coronary disease

    International Nuclear Information System (INIS)

    Zhao Qian; Li Juan

    2007-01-01

    The morbidity of diabetes mellitus is gradually increasing. It's most important complication is cardiovascular disease. The coronary disease is the main cause of death in patients with diabetes mellitus. The stress myocardial perfusion imaging help diagnose diabetic coronary disease and prognosis judgement and risk assessment. So it can improve the living standard of patients with diabetes mellitus, and decrease the mortality of diabetes mellitus. (authors)

  15. Timed Rise from Floor as a Predictor of Disease Progression in Duchenne Muscular Dystrophy: An Observational Study.

    Directory of Open Access Journals (Sweden)

    Elena S Mazzone

    Full Text Available The role of timed items, and more specifically, of the time to rise from the floor, has been reported as an early prognostic factor for disease progression and loss of ambulation. The aim of our study was to investigate the possible effect of the time to rise from the floor test on the changes observed on the 6MWT over 12 months in a cohort of ambulant Duchenne boys.A total of 487 12-month data points were collected from 215 ambulant Duchenne boys. The age ranged between 5.0 and 20.0 years (mean 8.48 ±2.48 DS.The results of the time to rise from the floor at baseline ranged from 1.2 to 29.4 seconds in the boys who could perform the test. 49 patients were unable to perform the test at baseline and 87 at 12 month The 6MWT values ranged from 82 to 567 meters at baseline. 3 patients lost the ability to perform the 6mwt at 12 months. The correlation between time to rise from the floor and 6MWT at baseline was high (r = 0.6, p<0.01.Both time to rise from the floor and baseline 6MWT were relevant for predicting 6MWT changes in the group above the age of 7 years, with no interaction between the two measures, as the impact of time to rise from the floor on 6MWT change was similar in the patients below and above 350 m. Our results suggest that, time to rise from the floor can be considered an additional important prognostic factor of 12 month changes on the 6MWT and, more generally, of disease progression.

  16. Cone rod dystrophies

    Science.gov (United States)

    Hamel, Christian P

    2007-01-01

    Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently

  17. Cone rod dystrophies

    Directory of Open Access Journals (Sweden)

    Hamel Christian P

    2007-02-01

    Full Text Available Abstract Cone rod dystrophies (CRDs (prevalence 1/40,000 are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP, also called the rod cone dystrophies (RCDs resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7. Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far. The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs, CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs, and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs. It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is

  18. Clinical aspects, molecular pathomechanisms and management of myotonic dystrophies

    OpenAIRE

    Meola, G.

    2013-01-01

    Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) was described more than 100 years ago and is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) was identified only 18 years ago and is caused by a (CCTG)n expansion in ZNF9/CNBP....

  19. Results of RNV studies and /sup 201/Tl myocardial scintigraphy in patients with progressive systemic scleroderma (PSS)

    Energy Technology Data Exchange (ETDEWEB)

    Ammari, B.; Hotze, A.; Gruenwald, F.; Biersack, H.J.; Biltz, H.; Kuester, W.

    1988-12-01

    Prognosis of progressive systemic scleroderma (PSS) depends directly on the extent of visceral organ involvement, and in particular, on the cardiac, renal and pulmonary appearance. Therapeutic approaches therefore require periodic followup with non-invasive methods to evaluate the actual course of disease and the success of therapy. Tl-201 scintigraphy showed pathologic heart abnormalities in 47% and RNV in 23% of the PSS patients. Our results and published data reveal the sensitivity of both myocardial scans and RNV in the evaluation of patients with PSS. Other current methods for the diagnosis of heart diseases, however, such as echocardiography should also be performed. In patients with PSS coronary angiography, however, usually shows normal coronary vessels.

  20. Impaired fetal muscle development and JAK-STAT activation mark disease onset and progression in a mouse model for merosin-deficient congenital muscular dystrophy.

    Science.gov (United States)

    Nunes, Andreia M; Wuebbles, Ryan D; Sarathy, Apurva; Fontelonga, Tatiana M; Deries, Marianne; Burkin, Dean J; Thorsteinsdóttir, Sólveig

    2017-06-01

    Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a dramatic neuromuscular disease in which crippling muscle weakness is evident from birth. Here, we use the dyW mouse model for human MDC1A to trace the onset of the disease during development in utero. We find that myotomal and primary myogenesis proceed normally in homozygous dyW-/- embryos. Fetal dyW-/- muscles display the same number of myofibers as wildtype (WT) muscles, but by E18.5 dyW-/- muscles are significantly smaller and muscle size is not recovered post-natally. These results suggest that fetal dyW-/- myofibers fail to grow at the same rate as WT myofibers. Consistent with this hypothesis between E17.5 and E18.5 dyW-/- muscles display a dramatic drop in the number of Pax7- and myogenin-positive cells relative to WT muscles, suggesting that dyW-/- muscles fail to generate enough muscle cells to sustain fetal myofiber growth. Gene expression analysis of dyW-/- E17.5 muscles identified a significant increase in the expression of the JAK-STAT target gene Pim1 and muscles from 2-day and 3-week old dyW-/- mice demonstrate a dramatic increase in pSTAT3 relative to WT muscles. Interestingly, myotubes lacking integrin α7β1, a laminin-receptor, also show a significant increase in pSTAT3 levels compared with WT myotubes, indicating that α7β1 can act as a negative regulator of STAT3 activity. Our data reveal for the first time that dyW-/- mice exhibit a myogenesis defect already in utero. We propose that overactivation of JAK-STAT signaling is part of the mechanism underlying disease onset and progression in dyW-/- mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Limb girdle muscular dystrophies

    DEFF Research Database (Denmark)

    Vissing, John

    2016-01-01

    PURPOSE OF REVIEW: The aim of the study was to describe the clinical spectrum of limb girdle muscular dystrophies (LGMDs), the pitfalls of the current classification system for LGMDs, and emerging therapies for these conditions. RECENT FINDINGS: Close to half of all LGMD subtypes have been...... or are registered in other classification systems for muscle disease. On the contrary, diseases that fulfill classical criteria for LGMD have found no place in the LGMD classification system. These shortcomings call for revision/creation of a new classification system for LGMD. The rapidly expanding gene sequencing...... capabilities have helped to speed up new LGMD discoveries, and unveiled pheno-/genotype relations. Parallel to this progress in identifying new LGMD subtypes, emerging therapies for LGMDs are under way, but no disease-specific treatment is yet available for nonexperimental use. SUMMARY: The field of LGMD...

  2. Evaluation of myocardial and skeletal muscular involvement with thallium-201 myocardial emission computed tomography and whole body scintigraphy

    International Nuclear Information System (INIS)

    Yamamoto, Shuhei; Matsushima, Hideo; Sotobata, Iwao; Suzuki, Akio; Indo, Toshikatsu; Matsuoka, Yukihiko

    1986-01-01

    Thallium-201 (Tl-201) myocardial emission computed tomography and whole body scintigraphy were performed using a rotating gamma camera in 64 patients with neurologic disease and 14 normal subjects. Thallium-201 myocardial perfusion defects were seen in 40 % of the muscular involvement in 47 patients with muscular dystrophy (MD), in whom morphological abnormality of the heart was common. There was strong relationship between the degree of left ventricular perfusion defects and the degree of pulmonary uptake of Tl-201. Thallium-201 whole body scintigraphy showed homogeneous distribution of Tl-201 in the extremities in normal subjects, and perfusion defects in 73 % of the muscular lesions in MD patients. Muscular and skeletal lesions for MD appear to progress independently. Thallium-201 imaging seems to be of clinical value in assessing the muscular and skeletal lesions. (Namekawa, K.)

  3. Radiographic features of Golden Retriever muscular dystrophy.

    Science.gov (United States)

    Brumitt, Jason W; Essman, Stephanie C; Kornegay, Joe N; Graham, John P; Weber, William J; Berry, Clifford R

    2006-01-01

    Golden Retriever muscular dystrophy is an inherited, degenerative myopathy due to the absence of dystrophin and is used as a model of Duchenne muscular dystrophy of young boys. This report describes the radiographic abnormalities of Golden Retriever muscular dystrophy in 26 dogs. The thoracic abnormalities included diaphragmatic asymmetry (18/26), diaphragmatic undulation (18/26), and gastro-esophageal hiatal hernia (6/26). Pelvic abnormalities included narrowing of the body of the ilia (14/19), ventral deviation and curvature of the tuber ischii (14/19), elongation of the obturator foramen with a decrease in opacity of the surrounding bone (12/19), and lateral flaring of the wings of the ilia (12/19). Abdominal abnormalities consisted of hepatomegaly (14/22) and poor serosal detail (12/22). The unique thoracic abnormalities were a consistent finding in affected Golden Retriever muscular dystrophy dogs. The diagnosis of muscular dystrophy should be included in the differential list if the combination of diaphragm undulation and asymmetry, and gastro-esophageal hiatal hernia are identified. These diaphragmatic abnormalities are related to hypertrophy and hyperplasia of the diaphragm. Additionally, the skeletal changes of pelvic tilt, elongation of the pelvis, widening of the obturator foramina and thinning of the ischiatic tables appear to be specific to Golden Retriever muscular dystrophy in dogs. These pelvic abnormalities are most likely secondary to bone remodeling associated with the progressive skeletal myopathy and subsequent contracture/fibrosis.

  4. Histopathologic Evolution of Cardiomyopathy in a Canine Model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Lygia M.M. Malvestio

    2015-07-01

    Full Text Available Duchenne muscular dystrophy (DMD is a recessive X-linked disorder characterized for mutation in dystrophin gene and manifested by progressive degeneration and necrosis of skeletal and cardiac muscle with replacement leading to generalized muscular weakness and atrophy. The dog Golden Retriever Muscular Dystrophy (GRMD is the best experimental model for DMD, with genotypic and phenotypic manifestations closely of human disease. Similar to patients with DMD, heart failure is a major cause of death in GRMD animals. The objective of this study was to evaluate the pathological progression of myocardial lesions from GRMD dogs in different ages in order to clarify the pathogenesis of Duchenne´s cardiomyopathy. Fragments of left and right ventricle and interventricular septum, from 18 GRMD dogs between 6 to 51 months were collected, fixed, dehydrated, clarified, and finally embedded in paraffin. Five micrometer thick serial sections were obtained and stained with Hematoxylin-Eosin (HE, Picrosirius red, and Von Kossa. Histological analyses were performed at the light microscopy. Myocardial lesions were observed in all GRMD dogs and the sequence of cardiac lesion classified according to according to the age included: abnormal calcium accumulation, myofibrillar necrosis, proliferation of granulation tissue, endomysial and perimysial fibrosis, and finally myocardial fatty infiltration. Interestingly, several Anitschkow cells, the hallmark of rheumatic carditis, were detected in inflammatory infiltrate present at granulation tissue. Our results demonstrate the sequence of cardiac lesions that determine the cardiomyopathy in Golden Retriever dogs affected by DMD and exhibit, for the first time, the Anitschkow cells in the histological findings of this cardiomyopathy. These results are relevant for to clarify the pathogenesis of cardiomyopathy in dogs and humans affected by DMD.

  5. Genetics Home Reference: Fukuyama congenital muscular dystrophy

    Science.gov (United States)

    ... with mental retardation Muscular dystrophy, congenital, Fukuyama type Muscular dystrophy, congenital, with central nervous system involvement Polymicrogyria with muscular dystrophy Related Information How ...

  6. A Drosophila model for Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Plas, Mariska Cathelijne van der

    2008-01-01

    Duchenne Muscular Dystrophy (DMD) is a severe X-linked disease characterized by progressive muscle wasting and sometimes mild mental retardation. The disease is caused by mutations in the dystrophin gene. DMD is correlated with the absence of Dp427, which is located along the sarcolemma in skeletal

  7. Duchenne muscular dystrophy models show their age

    OpenAIRE

    Chamberlain, Jeffrey S.

    2010-01-01

    The lack of appropriate animal models has hampered efforts to develop therapies for Duchenne muscular dystrophy (DMD). A new mouse model lacking both dystrophin and telomerase (Sacco et al., 2010) closely mimics the pathological progression of human DMD and shows that muscle stem cell activity is a key determinant of disease severity.

  8. Genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies.

    Science.gov (United States)

    Hightower, Rylie M; Alexander, Matthew S

    2018-01-01

    Muscular dystrophy is defined as the progressive wasting of skeletal muscles that is caused by inherited or spontaneous genetic mutations. Next-generation sequencing has greatly improved the accuracy and speed of diagnosis for different types of muscular dystrophy. Advancements in depth of coverage, convenience, and overall reduced cost have led to the identification of genetic modifiers that are responsible for phenotypic variability in affected patients. These genetic modifiers have been postulated to explain key differences in disease phenotypes, including age of loss of ambulation, steroid responsiveness, and the presence or absence of cardiac defects in patients with the same form of muscular dystrophy. This review highlights recent findings on genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies based on animal and clinical studies. These genetic modifiers hold great promise to be developed into novel therapeutic targets for the treatment of muscular dystrophies. Muscle Nerve 57: 6-15, 2018. © 2017 Wiley Periodicals, Inc.

  9. Identification of a gene expression core signature for Duchenne Muscular Dystrophy (DMD) via integrative analysis reveals novel potential compounds for treatment

    KAUST Repository

    Ichim-Moreno, Norú ; Aranda, Manuel; Voolstra, Christian R.

    2010-01-01

    Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy and one of the most prevalent genetic disorders of childhood. DMD is characterized by rapid progression of muscle degeneration, and ultimately death. Currently

  10. Quantitative study of myocardial microcirculation in arterial hypertension due to progressive inhibition of NO synthesis

    Directory of Open Access Journals (Sweden)

    Leila Maria Meirelles Pereira

    1999-11-01

    Full Text Available OBJECTIVE: To study the quantitative changes in intramyocardial blood vessels in rats in whom nitric oxide synthesis was inhibited. METHODS: Four groups of 10 rats were studied: control (C25 and C40 and L-NAME (L25 and L40. The animals L25 and L40 received L-NAME in the dosage of 50mg/kg/day for 25 and 40 days, respectively. On days 26 and 41 the animals in groups 25 and 40 were sacrificed. Analysis of the myocardium was performed using light microscopy and stereology. RESULTS: Arterial blood pressure and heart weight increased 74.5 and 57.8% after 25 days and 90.2 and 34.6% after 40 days, respectively. Comparing the L-NAME rats with the respective controls revealed that vessel volume density decreased 31.3% after 40 days, and the vessel length-density decreased 53.5% after 25 days and 25.7% after 40 days. The mean cross-sectional area of the vessels showed an important reduction of 154.6% after 25 days. The intramyocardial vessels decreased significantly in length- density in the L-NAME animals. The mean cross-sectional area of the vessels, which normally increases during heart growth between 25 and 40 days, showed a precocious increase by the 25th day in the L-NAME rats. This suggests an increase of the size of the heart, including blood vessels. CONCLUSION: The inhibition of the NO synthesis provokes rarefaction in the intramyocardial vessels that progresses with the time of administration of L-NAME.

  11. Evaluation of Limb-Girdle Muscular Dystrophy

    Science.gov (United States)

    2014-03-06

    Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency); Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency); Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

  12. Limb-Girdle Muscular Dystrophy (LGMD)

    Science.gov (United States)

    ... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

  13. Myocardial Bridge

    Science.gov (United States)

    ... Center > Myocardial Bridge Menu Topics Topics FAQs Myocardial Bridge En español Your heart is made of muscle, ... surface of the heart. What is a myocardial bridge? A myocardial bridge is a band of heart ...

  14. Muscular Dystrophy (MD)

    Science.gov (United States)

    ... patients may need assisted ventilation to treat respiratory muscle weakness and a pacemaker for cardiac abnormalities. View Full Treatment Information Definition The muscular dystrophies (MD) are a group of more than 30 ...

  15. Facioscapulohumeral muscular dystrophy

    Science.gov (United States)

    ... There is no known cure for facioscapulohumeral muscular dystrophy. Treatments are given to control symptoms and improve quality of life. Activity is encouraged. Inactivity such as bedrest can make the muscle disease worse. Physical therapy may help maintain muscle ...

  16. Cardiac involvement in myotonic muscular dystrophy (Steinert's disease): a prospective study of 25 patients

    International Nuclear Information System (INIS)

    Perloff, J.K.; Stevenson, W.G.; Roberts, N.K.; Cabeen, W.; Weiss, J.

    1984-01-01

    The presence, degree and frequency of disorders of cardiac conduction and rhythm and of regional or global myocardial dystrophy or myotonia have not previously been studied prospectively and systematically in the same population of patients with myotonic dystrophy. Accordingly, 25 adults with classic Steinert's disease underwent electrocardiography, 24-hour ambulatory electrocardiography, vectorcardiography, chest x-rays, echocardiography, electrophysiologic studies, and technetium-99m angiography. Clinically important cardiac manifestations of myotonic dystrophy reside in specialized tissues rather than in myocardium. Involvement is relatively specific, primarily assigned to the His-Purkinje system. The cardiac muscle disorder takes the form of dystrophy rather than myotonia, and is not selective, appearing with approximately equal distribution in all 4 chambers. Myocardial dystrophy seldom results in clinically overt ventricular failure, but may be responsible for atrial and ventricular arrhythmias. Since myotonic dystrophy is genetically transmitted, a primary biochemical defect has been proposed with complete expression of the gene toward striated muscle tissue, whether skeletal or cardiac. Specialized cardiac tissue and myocardium have close, if not identical, embryologic origins, so it is not surprising that the genetic marker affects both. Cardiac involvement is therefore an integral part of myotonic dystrophy, targeting particularly the infranodal conduction system, to a lesser extent the sinus node, and still less specifically, the myocardium

  17. Rhabdomyolysis featuring muscular dystrophies.

    Science.gov (United States)

    Lahoria, Rajat; Milone, Margherita

    2016-02-15

    Rhabdomyolysis is a potentially life threatening condition of various etiology. The association between rhabdomyolysis and muscular dystrophies is under-recognized in clinical practice. To identify muscular dystrophies presenting with rhabdomyolysis at onset or as predominant feature. We retrospectively reviewed clinical and laboratory data of patients with a genetically confirmed muscular dystrophy in whom rhabdomyolysis was the presenting or main clinical manifestation. Thirteen unrelated patients (males=6; females=7) were identified. Median age at time of rhabdomyolysis was 18 years (range, 2-47) and median duration between the first episode of rhabdomyolysis and molecular diagnosis was 2 years. Fukutin-related protein (FKRP) muscular dystrophy (n=6) was the most common diagnosis, followed by anoctaminopathy-5 (n=3), calpainopathy-3 (n=2) and dystrophinopathy (n=2). Four patients experienced recurrent rhabdomyolysis. Eight patients were asymptomatic and 3 reported myalgia and exercise intolerance prior to the rhabdomyolysis. Exercise (n=6) and fever (n=4) were common triggers; rhabdomyolysis was unprovoked in 3 patients. Twelve patients required hospitalization. Baseline CK levels were elevated in all patients (median 1200 IU/L; range, 600-3600). Muscular dystrophies can present with rhabdomyolysis; FKRP mutations are particularly frequent in causing such complication. A persistently elevated CK level in patients with rhabdomyolysis warrants consideration for underlying muscular dystrophy. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Glycosaminoglycan modifications in Duchenne muscular dystrophy: specific remodeling of chondroitin sulfate/dermatan sulfate

    NARCIS (Netherlands)

    Negroni, E.; Henault, E.; Chevalier, F.; Gilbert-Sirieix, M.; Kuppevelt, T.H. van; Papy-Garcia, D.; Uzan, G.; Albanese, P.

    2014-01-01

    Widespread skeletal muscle degeneration and impaired regeneration lead to progressive muscle weakness and premature death in patients with Duchenne muscular dystrophy (DMD). Dystrophic muscles are progressively replaced by nonfunctional tissue because of exhaustion of muscle precursor cells and

  19. Learning about Duchenne Muscular Dystrophy

    Science.gov (United States)

    ... protein. Often these boys are classified as having Becker muscular dystrophy. Genetic testing (looking at the body's genetic instructions) ... National Library of Medicine Web site Duchenne and Becker muscular dystrophy [ghr.nlm.nih.gov] From Genetics Home Reference ...

  20. Disability and Survival in Duchenne Muscular Dystrophy

    OpenAIRE

    Kohler, M; Clarenbach, C F; Bahler, C; Brack, T; Russi, E W; Bloch, K E

    2009-01-01

    BACKGROUND: Duchenne muscular dystrophy (DMD) leads to progressive impairment of muscle function, respiratory failure and premature death. Longitudinal data on the course of physical disability and respiratory function are sparse. OBJECTIVES: To prospectively assess physical impairment and disability, respiratory function and survival in DMD patients over several years in order to describe the course of the disease with current care. METHODS: In 43 patients with DMD, aged 5-35 years, yearly a...

  1. Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

    Science.gov (United States)

    Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

    2017-12-01

    Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Cardiac abnormalities in a follow-up study on carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    van Westrum, S. M. Schade; Hoogerwaard, E. M.; Dekker, L.; Standaar, T. S.; Bakker, E.; Ippel, P. F.; Oosterwijk, J. C.; Majoor-Krakauer, D. F.; van Essen, A. J.; Leschot, N. J.; Wilde, A. A. M.; de Haan, R. J.; de Visser, M.; van der Kooi, A. J.

    Objectives: Cardiac involvement has been reported in carriers of dystrophin mutations giving rise to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The progress of these abnormalities during long-term follow-up is unknown. We describe the long-term follow-up of dilated

  3. Adult patient with Becker dystrophy undergoing orthopedic surgery: an anesthesia challenge.

    Science.gov (United States)

    Parish, Masoud; Farzin, Haleh

    2018-01-01

    Muscular dystrophies are considered to be a series of neuromuscular diseases with genetic causes and are characterized by progressive muscle weakness and degeneration of the skeletal muscle. The case of an adult man with Becker dystrophy referred for repair of the patella tendon tearing and patella fracture is described. He underwent successful surgery using total intravenous anesthesia without any complications.

  4. Cardiac abnormalities in a follow-up study on carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    Schade van Westrum, S. M.; Hoogerwaard, E. M.; Dekker, L.; Standaar, T. S.; Bakker, E.; Ippel, P. F.; Oosterwijk, J. C.; Majoor-Krakauer, D. F.; van Essen, A. J.; Leschot, N. J.; Wilde, A. A. M.; de Haan, R. J.; de Visser, M.; van der Kooi, A. J.

    2011-01-01

    Objectives: Cardiac involvement has been reported in carriers of dystrophin mutations giving rise to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The progress of these abnormalities during long-term follow-up is unknown. We describe the long-term follow-up of dilated

  5. Meeting the Assistive Technology Needs of Students with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Heller, Kathryn Wolff; Mezei, Peter J.; Avant, Mary Jane Thompson

    2009-01-01

    Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

  6. Urological manifestations of Duchenne muscular dystrophy.

    Science.gov (United States)

    Askeland, Eric J; Arlen, Angela M; Erickson, Bradley A; Mathews, Katherine D; Cooper, Christopher S

    2013-10-01

    Duchenne muscular dystrophy is a dystrophinopathy affecting males that is associated with multiple organ system complications. To our knowledge urological complications of Duchenne muscular dystrophy have been described only anecdotally to date. We reviewed the medical charts of 135 patients with Duchenne or Duchenne-Becker muscular dystrophy for demographics and disease progression, urological diagnoses, intervention and followup. Of 135 patients 67 (50%) had at least 1 documented urological diagnosis and 38 (28%) had multiple manifestations. Lower urinary tract symptoms were the most common urological diagnosis (32% of patients). Survival analysis revealed a median age at onset of lower urinary tract symptoms of 23 years (95% CI 17.7-23.9). Intervention was required in 12 patients (9%), most commonly due to nephrolithiasis. Urological morbidity increased with Duchenne muscular dystrophy progression when stratified by clinical progression. Lower urinary tract symptoms were more common in nonambulatory patients (40.7% vs 19%, p = 0.007), those with a diagnosis of scoliosis (44% vs 19.7%, p = 0.003) and/or scoliosis spine surgery (60% vs 22%, p <0.001), and those on invasive respiratory support (53% vs 29%, p = 0.046). Likewise, nephrolithiasis was more common in nonambulatory patients (10% vs 0%, p = 0.017), those with scoliosis (12% vs 0%, p = 0.004) and/or scoliosis spine surgery (20% vs 1%, p <0.001), and those on invasive respiratory support (29% vs 3%, p <0.001). Only 28% of patients with a urological manifestation were referred to urology. As these patients transition into adolescence and adulthood, the increased prevalence of urological manifestations warrants increased awareness and referral to urologists. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  7. Meaning of Muscular Dystrophy

    Science.gov (United States)

    ... is very similar to Duchenne, except kids with Becker MD may not have problems until much later, when they're teenagers or adults. It takes a long time for their muscles to become weak. How Does a Kid Get Muscular Dystrophy? MD is not contagious (say: con-TAY-juss), ...

  8. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Raman, Subha V; Hor, Kan N; Mazur, Wojciech; Halnon, Nancy J; Kissel, John T; He, Xin; Tran, Tam; Smart, Suzanne; McCarthy, Beth; Taylor, Michael D; Jefferies, John L; Rafael-Fortney, Jill A; Lowe, Jeovanna; Roble, Sharon L; Cripe, Linda H

    2015-02-01

    Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1·0 [IQR 0·3-2·2] vs 2·2 [1·3-3·1]; p=0·020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in

  9. Prevalence of muscular dystrophy in patients with muscular disorders in Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Khadijeh Hajinaghi Tehrani

    2018-05-01

    Full Text Available Muscular dystrophy is a group of diseases that is characterized by progressive muscle wasting and the weakness of variable distribution and severity. On the basis of the distribution of predominant muscle weakness, there are many different kinds of muscular dystrophy. Some dystrophies are especially frequent in certain populations. There are no studies on the prevalence of muscular dystrophy in Iran. This study was aimed to survey the prevalence of muscular dystrophy among Iranian patients with muscular disorders. This analytical cross-sectional study was conducted on 1000 patients with musculoskeletal disorders who visited the dystrophy association of Bou-Ali Hospital (Tehran from June 2014 to June 2016. Patients’ data were extracted using a checklist that included age, gender, age of onset, family history, findings from clinical diagnostic tests and types of muscular dystrophy. The clinical findings were the results of genetic tests; EMG-NCV; para-clinical findings, including LDH and CPK; and pathological findings. All data were analyzed by SPSS V.22 (IBM Inc., NY with Chi Square and One way ANOVA tests. All analyses were performed with P = 0.05 considered as the threshold of statistical significant. Out of the 337 patients studied, 262 (77.7% were male and 75 (22.3% were female. Subjects had a mean (± SD age of 26.08 (± 11.86 years with an age range of 3 to 59 years. The most common types of muscular dystrophy were found to be Duchenne dystrophy (131 cases, 38.9%, limb-girdle dystrophy (91 cases, 27%, Becker dystrophy (58 cases, 17.2%, FSHD dystrophy (31 cases, 9.2%, and SMA (26 cases, 7.7%, respectively. The results showed that a statistically significant relationship between dystrophy types and gender, age, family history, age of diagnosis, CPK and LDH levels (P < 0.001. There were no statistical relationship between dystrophy types and pathological findings (P = 0.57, EMG-NCV test results (P = 0.062, and genetic findings (P = 0

  10. [Human myopathy and animal muscular dystrophy].

    Science.gov (United States)

    Schapira, G; Dreyfus, J C; Schapira, F

    1977-08-01

    Two hereditary muscular dystrophies similar to human progressive muscular dystrophy (P.M.D. Duchenne type) have been isolated in animals, one in mouse, the other in chicken. The decrease in the activity of glycogenolytic enzymes is similar to that observed in denervated muscle. Isozymic fetal types for several muscular enzymes have been observed as well in chicken as in man, but this fetal type may also be found in neurogenic atrophy. The release in circulation of muscle enzymes seems more specific. But the origin of the genetic lesion is still unknown. We describe here the three different theories about this problem: i.e. neurogenic, vascular, or myogenic. This last theory implies a trouble of membrane permeability.

  11. Prevalence of cardiomyopathy in duchenne and becker's muscular dystrophy

    International Nuclear Information System (INIS)

    Sultan, A.; Fayaz, M.

    2008-01-01

    Cardiac assessment was not done routinely in Duchenne (DMD) and Becker muscular dystrophy (BMD) patients in Northern region of England while evidence was gathering on progressive cardiomyopathy in these patients. We wanted to find out the prevalence, progression and clinical features of cardiac involvement in Duchenne and Becker muscular dystrophy. Methods: It is a retrospective review of clinical, electrocardiographic and echocardiographic assessments. The notes of 52 Duchenne and Becker muscular dystrophy patients were reviewed out of which 32 had DMD, 6 had Intermediate muscular dystrophy (IMD) and 14 had BMD. Prevalence of preclinical and clinically evident cardiac involvement was 88.4% in DMD and BMD patients. Sixty nine% of patients had clinically evident cardiac involvement but only four patients had cardiac symptoms in the form of palpitations, out of which two were due to respiratory dysfunction and others was due to cardiac failure. Clinical examination of the rest of all of the patients was unremarkable. Electrocardiogram was abnormal in 88.4% of patients. Conduction defects were found in 19.4% of patients. Echocardiogram was abnormal in 80.7% of patients but all were poor echo subjects including those who had normal echocardiogram. Though most patients were asymptomatic, a high percentage had evidence of preclinical and clinically evident cardiac involvement. So in all patients with Xp21 linked muscular dystrophy a routine baseline cardiac assessment should be done at the age of 10 years and reviewed after intervals of one to two years. (author)

  12. A newly recognized autosomal dominant limb girdle muscular dystrophy with cardiac involvement

    NARCIS (Netherlands)

    van der Kooi, A. J.; Ledderhof, T. M.; de Voogt, W. G.; Res, C. J.; Bouwsma, G.; Troost, D.; Busch, H. F.; Becker, A. E.; de Visser, M.

    1996-01-01

    Sixty-five members of three families with limb girdle muscular dystrophy (LGMD) underwent neurological, cardiological, and ancillary investigations. Thirty-five individuals were diagnosed as having slowly progressive autosomal dominant LGMD. Symmetrical weakness started in the proximal lower limb

  13. Potentialities of using 201Tl-chloride in the differential diagnosis of coronarogenic and extraconarogenic myocardial lesions in menopausal females

    International Nuclear Information System (INIS)

    Voronin, V.A.; Nechaev, D.D.; Laskin, S.A.; Martynov, I.V.; Petukhova, G.S.

    1991-01-01

    76 menopausal females were subjected to general clinical examination: biochemical investigation of carbohydrate, protein and lipid metabolism; radioimmunoassay of hormones; myocardial scintigraphy with 201 Tl-chloride to diagnose coronarogenic and extracoronarogenic myocardial lesions. It is shown that the application of myocardial scintigraphy with 201 Tl-chloride in menopausal females has followed to clarify the degree of distrophic changes in the myocardium of the left ventricle and to differentiate dyshormonal dystrophy and myocardial ischemia

  14. Dysphagia in Duchenne Muscular Dystrophy Assessed by Validated Questionnaire

    Science.gov (United States)

    Archer, Sally K.; Garrod, Rachel; Hart, Nicholas; Miller, Simon

    2013-01-01

    Background: Duchenne muscular dystrophy (DMD) leads to progressive muscular weakness and death, most typically from respiratory complications. Dysphagia is common in DMD; however, the most appropriate swallowing assessments have not been universally agreed and the symptoms of dysphagia remain under-reported. Aims: To investigate symptoms of…

  15. Quantitative assessment of calf circumference in Duchenne muscular dystrophy patients

    NARCIS (Netherlands)

    Beenakker, EAC; de Vries, Joeke; Fock, JM; van Tol, M; Brouwer, OF; Maurits, NM; van der Hoeven, JH

    2002-01-01

    Duchenne muscular dystrophy is clinically characterised by progressive muscle weakness and a gradual increase in the size of some affected muscles, especially calf muscles. The extent of calf enlargement is usually determined by subjective visual assessment. The purpose of this study was to

  16. Orocaecal transit time in Duchenne muscular dystrophy.

    OpenAIRE

    Korman, S H; Bar-Oz, B; Granot, E; Meyer, S

    1991-01-01

    Smooth muscle degeneration may occur in Duchenne muscular dystrophy. We measured fasting orocaecal transit time in patients with advanced Duchenne muscular dystrophy and other muscular dystrophies and in healthy controls. No significant differences were found. In contrast to reports of gastric hypomotility in Duchenne muscular dystrophy, we found no evidence of impaired small intestinal motility.

  17. Muscle-Eye-Brain Disease; a Rare Form of Syndromic Congenital Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Gosal Gurinder S

    2011-03-01

    Full Text Available Congenital muscular dystrophy (CMD is a heterogeneous group of disorders characterized by muscular hypotonia since birth and the histologic features of muscular dystrophy. Syndromic congenital muscular dystrophies are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We present a case of a rare form of syndromic congenital muscular dystrophy in an eight year old girl, born of first- degree consanguinity. She had: global developmental delay; a seizure disorder; hypotonia; progressive muscle contractures including bilateral symmetrical flexion contractures of hips, knees, equinus contracture and thoracolumbar scoliosis; diminished deep tendon reflexes: bilateral premature cataract; pseudophakia; and nystagmus. The patient was also highly myopic. Based on clinical features, muscle biopsy and MRI of the brain, a diagnosis of muscle- eye- brain disease was made. Identification of these patients may help to prevent this crippling disorder in the future siblings of probands by utilizing genetic counselling and mutation analysis.

  18. [DIAGNOSTIC VARIATIONS OF X-LINKED MUSCULAR DYSTROPHY WITH CONTRACTURES].

    Science.gov (United States)

    Kvirkvelia, N; Shakarishvili, R; Gugutsidze, D; Khizanishvili, N

    2015-01-01

    Case report with review describes X-linked muscular dystrophy with contractures in 28 years old man and his cousin. The disease revealed itself in an early stage (age 5-10), the process was progressing with apparent tendons retraction and contraction, limited movement in the areas of the neck and back of spine, atrophy of shoulder and pelvic yard and back muscles. Intellect was intact. Cardyomyopathy was exhibited. CK was normal. EMG showed classic myopathic features. Muscle biopsy showed different caliber groups of muscle fibers, growth of endo-perimesial connective tissue. Clinical manifestations together with electrophysiological and histological data suggest consistency with Rotthauwe-Mortier-Bayer X-linked muscular dystrophy.

  19. Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma

    International Nuclear Information System (INIS)

    Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Owens, G.R.; Steen, V.D.; Rodnan, G.P.

    1984-01-01

    Myocardial function and perfusion were evaluated in 22 patients with progressive systemic sclerosis with the CREST syndrome using exercise and radionuclide techniques, pulmonary function testing, and chest roentgenography. The results were compared with a similar study of 26 patients with progressive systemic sclerosis with diffuse scleroderma. The prevalence of thallium perfusion abnormalities was similar in the groups with CREST syndrome and diffuse scleroderma, (64 percent versus 77 percent), but the defects were significantly smaller in the CREST syndrome (p less than 0.01). Reperfusion thallium defects in the absence of extramural coronary artery disease were seen in 38 percent of patients with diffuse scleroderma. This finding was not seen in any of the patients with the CREST syndrome. In diffuse scleroderma, abnormalities of both right and left ventricular function were related to larger thallium perfusion defects. In the CREST syndrome, abnormalities of left ventricular function were minor, were seen only during exercise, and were unrelated to thallium perfusion defects. Abnormal resting right ventricular function was seen in 36 percent of the patients with the CREST syndrome and was associated with an isolated decrease in diffusing capacity of carbon monoxide. It is concluded that the cardiac manifestations of the CREST syndrome are distinct from those found in diffuse scleroderma. Unlike diffuse scleroderma, abnormalities of left ventricular function in the CREST syndrome are minor and are unrelated to abnormalities of coronary perfusion. Right ventricular dysfunction in the CREST syndrome appears to be primarily related to pulmonary vascular disease

  20. Iodine 123-labeled meta-iodobenzylguanidine myocardial scintigraphy in the cases of idiopathic Parkinson`s disease, multiple system atrophy, and progressive supranuclear palsy

    Energy Technology Data Exchange (ETDEWEB)

    Yoshita, Mitsuhiro; Hayashi, Michiyuki; Hirai, Shunsaku [Tokyo Metropolitan Neurological Hospital (Japan)

    1997-06-01

    To investigate cardiac sympathetic function in Parkinson`s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP), {sup 123}I-MIBG myocardial scintigraphy was performed in 25 patients with PD, 25 patients with MSA, 14 patients with PSP, and 20 control subjects. In planar imaging studies, the heart-to-mediastinum average count ratio (H/M) was calculated for both early and delayed images. The mean value of H/M in patients with PD was significantly lower than in those with MSA, PSP, or no disease. Regardless of disease severity or intensity of anti-parkinsonian pharmacotherapy, mean values for H/M were always low in patients with PD. The mean values of H/M in patients with MSA and PSP were significantly lower than in controls. There was no significant difference between the mean value of H/M in MSA with orthostatic hypotension (OH) and that in MSA without OH, and also there was no significant difference between the mean value of H/M in MSA with striatonigral degeneration and that in MSA with olivopontocerebellar atrophy. Although the mean value of H/M in PSP with amitriptyline treatment was significantly lower than that in PSP patients without amitriptyline treatment, there was no significant difference between the mean value of H/M in PSP patients without amitriptyline treatment and that in controls. There was no correlation between H/M and disease duration in those three akinetic-rigid disorders that we have studied here. Thus, PD may have an abnormality of cardiac sympathetic function which has not been detected by previous cardiovascular autonomic studies. Particularly in early stages, {sup 123}I-MIBG myocardial scintigraphy may help to differentiate PD from MSA and PSP. (K.H.)

  1. Bilateral nanophthalmos and pigmentary retinal dystrophy--an unusual syndrome.

    Science.gov (United States)

    Proença, Helena; Castanheira-Dinis, A; Monteiro-Grillo, M

    2006-09-01

    To report the clinical picture of the rare association of nanophthalmos and pigmentary retinal dystrophy and its cataract surgery outcome. We report a case of a 60-year-old female who presented with bilateral slowly progressive visual loss. The patient presented with bilateral light perception visual acuity, exotropia, brunescent cataract hindering fundus examination and hypodontia. Ultrasonography revealed bilateral nanophthalmos. A visual-evoked potential was also performed preoperatively. Cataract surgery with +40D IOL implantation was uneventful. Postoperative fundus examination revealed pigmentary retinal dystrophy, confirmed by electrophysiologic tests. Glycosaminoglycan urinary excretion was normal. Congenital bilateral nanophthalmos may rarely be associated with pigmentary retinal dystrophy. We suggest thorough preoperative evaluation in nanophthalmic eyes for the exclusion of significant features concerning visual prognosis.

  2. Genetics Home Reference: Duchenne and Becker muscular dystrophy

    Science.gov (United States)

    ... Conditions Duchenne and Becker muscular dystrophy Duchenne and Becker muscular dystrophy Printable PDF Open All Close All Enable Javascript ... dystrophy occur almost exclusively in males. Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused ...

  3. Adult patient with Becker dystrophy undergoing orthopedic surgery: an anesthesia challenge

    Directory of Open Access Journals (Sweden)

    Parish M

    2018-02-01

    Full Text Available Masoud Parish, Haleh Farzin Anesthesiology Department, Tabriz University of Medical Sciences, Shohada Teaching Hospital, Tabriz, Iran Abstract: Muscular dystrophies are considered to be a series of neuromuscular diseases with genetic causes and are characterized by progressive muscle weakness and degeneration of the skeletal muscle. The case of an adult man with Becker dystrophy referred for repair of the patella tendon tearing and patella fracture is described. He underwent successful surgery using total intravenous anesthesia without any complications. Keywords: Becker dystrophy, orthopedic surgery, adult, intravenous anesthesia

  4. Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ: electrocardiographic, echocardiographic, and morphologic studies

    Directory of Open Access Journals (Sweden)

    Machida Noboru

    2006-12-01

    Full Text Available Abstract Background Cardiac mortality in Duchenne muscular dystrophy (DMD has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD has attracted much attention as an animal model because it resembles DMD, but GRMD is very difficult to maintain because of their severe phenotypes. We therefore established a line of dogs with Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ and examined the cardiac involvement. Methods The cardiac phenotypes of eight CXMDJ and four normal male dogs 2 to 21 months of age were evaluated using electrocardiography, echocardiography, and histopathological examinations. Results Increases in the heart rate and decreases in PQ interval compared to a normal littermate were detected in two littermate CXMDJ dogs at 15 months of age or older. Distinct deep Q-waves and increase in Q/R ratios in leads II, III, and aVF were detected by 6–7 months of age in all CXMDJ dogs. In the echocardiogram, one of eight of CXMDJ dogs showed a hyperechoic lesion in the left ventricular posterior wall at 5 months of age, but the rest had not by 6–7 months of age. The left ventricular function in the echocardiogram indicated no abnormality in all CXMDJ dogs by 6–7 months of age. Histopathology revealed myocardial fibrosis, especially in the left ventricular posterobasal wall, in three of eight CXMDJ dogs by 21 months of age. Conclusion Cardiac involvement in CXMDJ dogs is milder and has slower progression than that described in GRMD dogs. The distinct deep Q-waves have been ascribed to myocardial fibrosis in the posterobasal region of the left ventricle, but our data showed that they precede the lesion on echocardiogram and

  5. Muscular Dystrophy: Hope Through Research

    Science.gov (United States)

    ... of muscular dystrophy appeared in 1830, when Sir Charles Bell wrote an essay about an illness that ... linked disorder to their sons but their daughters will be carriers of that disorder. Carrier females occasionally ...

  6. Translational Research for Muscular Dystrophy

    Science.gov (United States)

    2012-05-01

    muscle dystrophy with abnormal waddling gait at 4 weeks of age. At 10 weeks of age, double mutants exhibit skeletal muscle degeneration, necrosis... dystrophy (MCMD). Homozygous dyW mice are passive, small, and emaciated, and demonstrate partial hindleg weakness and clasping. Their muscles contain...was statistically significant for both single- treatment groups. Figure 4. Effect of GW and AICAR on body mass, muscle mass, and behavioral

  7. Duchenne muscular dystrophy carriers

    International Nuclear Information System (INIS)

    Matsumura, K.; Nakano, I.

    1989-01-01

    By means of magnetic resonance imaging (MRI), the proton spin-lattice relaxation times (T1 values) of the skeletal muscles were measured in Duchenne muscular dystrophy (DMD) carriers and normal controls. The bound water fraction (BWF) was calculated from the T1 values obtained, according to the fast proton diffusion model. In the DMD carriers, T1 values of the gluteus maximus and quadriceps femoris muscles were significantly higher, and BWFs of these muscles were significantly lower than in normal control. Degenerative muscular changes accompanied by interstitial edema were presumed responsible for this abnormality. No correlation was observed between the muscle T1 and serum creatine kinase values. The present study showed that MRI could be a useful method for studying the dynamic state of water in both normal and pathological skeletal muscles. Its possible utility for DMD carrier detection was discussed briefly. (orig.)

  8. Evaluation of cardiac function in patients with Duchenne's muscular dystrophy by single photon emission computed tomography (SPECT)

    Energy Technology Data Exchange (ETDEWEB)

    Tamura, Takuhisa; Motomura, Masakatsu; Kanazawa, Hajime; Shibuya, Noritoshi (Kawatana Byoin National Sanatorium, Nagasaki (Japan))

    1989-06-01

    The extent of myocardial ischemia was evaluated in 20 patients with Duchenne's muscular dystrophy (DMD) by using Bull's eye method of thallium-201 myocardial SPECT. It was examined in relation to skeletal muscle involvement, age, left ventricular (LV) ejection fraction and ventricular premature contractions (VPCs). Myocardial ischemia was detected in all of patients with DMD. Ischemic lesion was mostly detected in the apical side of the LV lateral wall and interventricular septum, while the extent of myocardial ischemia had no correlations with either the stage of functional disability of skeletal muscle or age. The more ischemic ratio was higher, the more LV ejection fraction decreased. The total number of VPCs was relatively small and it did not have any relation to myocardial ischemic ratio. These results suggest that younger DMD patients having extensive myocardial ischemia and/or ventricular tachycardia will have a high risk of cardiac death. (author).

  9. Evaluation of cardiac function in patients with Duchenne's muscular dystrophy by single photon emission computed tomography (SPECT)

    International Nuclear Information System (INIS)

    Tamura, Takuhisa; Motomura, Masakatsu; Kanazawa, Hajime; Shibuya, Noritoshi

    1989-01-01

    The extent of myocardial ischemia was evaluated in 20 patients with Duchenne's muscular dystrophy (DMD) by using Bull's eye method of thallium-201 myocardial SPECT. It was examined in relation to skeletal muscle involvement, age, left ventricular (LV) ejection fraction and ventricular premature contractions (VPCs). Myocardial ischemia was detected in all of patients with DMD. Ischemic lesion was mostly detected in the apical side of the LV lateral wall and interventricular septum, while the extent of myocardial ischemia had no correlations with either the stage of functional disability of skeletal muscle or age. The more ischemic ratio was higher, the more LV ejection fraction decreased. The total number of VPCs was relatively small and it did not have any relation to myocardial ischemic ratio. These results suggest that younger DMD patients having extensive myocardial ischemia and/or ventricular tachycardia will have a high risk of cardiac death. (author)

  10. Genetics Home Reference: cone-rod dystrophy

    Science.gov (United States)

    ... common cause of autosomal recessive cone-rod dystrophy , accounting for 30 to 60 percent of cases. At ... dystrophy play essential roles in the structure and function of specialized light receptor cells (photoreceptors) in the ...

  11. Respiratory function in facioscapulohumeral muscular dystrophy 1

    NARCIS (Netherlands)

    Wohlgemuth, M.; Horlings, G.C.; Kooi, E.L. van der; Gilhuis, H.J.; Hendriks, J.C.M.; Maarel, S.M. van der; Engelen, B.G.M. van; Heijdra, Y.F.; Padberg, G.W.A.M.

    2017-01-01

    To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory

  12. What Are the Types of Muscular Dystrophy?

    Science.gov (United States)

    ... muscular dystrophy? There are more than 30 forms of muscular dystrophy (MD), with information on the primary types included in the table below. 1 Duchenne (DMD) What It Is Common Symptoms How It ...

  13. Abnormal sympathetic innervation of the heart in a patient with Emery-Dreifuss muscular dystrophy.

    Science.gov (United States)

    Fujiita, Takashi; Shimizu, Masami; Kaku, Bunji; Kanaya, Hounin; Horita, Yuki; Uno, Yoshihide; Yamazaki, Tsukasa; Ohka, Takio; Sakata, Kenji; Mabuchi, Hiroshi

    2005-07-01

    A 33-year-old man was admitted for general malaise and vomiting. An electrocardiogram showed a complete atrioventricular block and an echocardiogram showed right atrial dilatation and normal wall motion of left ventricle (LV). Gene analysis showed nonsense mutation in the STA gene, which codes for emerin, and Emery-Dreifuss muscular dystrophy was diagnosed. An endomyocardial biopsy of right ventricle showed mild hypertrophy of myocytes. Myocardial scintigraphic studies with Tc-99m methoxyisobutylisonitrile (MIBI) and I-123-betamethyl-p-iodophenylpentadecanoic acid (BMIPP) scintigrams showed no abnormalities. In contrast, I-123 metaiodobenzylguanidine (MIBG) scintigrams showed a diffuse and severe decrease in accumulation of MIBG in the heart. Six months later, his LV wall motion on echocardiograms developed diffuse hypokinesis. These results suggest that the abnormality on I-123 MIBG myocardial scintigrams may predict LV dysfunction in Emery-Dreifuss muscular dystrophy.

  14. Duchenne and Becker muscular dystrophy in adolescents: current perspectives

    Directory of Open Access Journals (Sweden)

    Andrews JG

    2018-03-01

    Full Text Available Jennifer G Andrews, Richard A Wahl Department of Pediatrics, University of Arizona, Tucson, AZ, USA Abstract: Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are life-limiting and progressive neuromuscular conditions with significant comorbidities, many of which manifest during adolescence. BMD is a milder presentation of the condition and much less prevalent than DMD, making it less represented in the literature, or more severely affected individuals with BMD may be subsumed into the DMD population using clinical cutoffs. Numerous consensus documents have been published on the clinical management of DMD, the most recent of which was released in 2010. The advent of these clinical management consensus papers, particularly respiratory care, has significantly increased the life span for these individuals, and the adolescent years are now a point of transition into adult lives, rather than a period of end of life. This review outlines the literature on DMD and BMD during adolescence, focusing on clinical presentation during adolescence, impact of living with a chronic illness on adolescents, and the effect that adolescents have on their chronic illness. In addition, we describe the role that palliative-care specialists could have in improving outcomes for these individuals. The increasing proportion of individuals with DMD and BMD living into adulthood underscores the need for more research into interventions and intracacies of adolescence that can improve the social aspects of their lives. Keywords: adolescent health, review, Duchenne muscular dystrophy, Becker muscular dystrophy, dystrophinopathy, palliative care

  15. Muscular dystrophies: key elements for everyday diagnosis and management

    Directory of Open Access Journals (Sweden)

    Alberto Palladino

    2013-12-01

    Full Text Available Muscular dystrophies are a heterogeneous group of inherited disorders that share similar clinical features and dystrophic changes on muscle biopsy, associated with progressive weakness. Weakness may be noted at birth or develop in late adult life. In recent years, cardiac involvement has been observed in a growing number of genetic muscle diseases, and considerable progress has been made in understanding the relationships between disease skeletal muscle and cardiac muscle disease. This review will focus on the skeletal muscle diseases most commonly associated with cardiac complications that can be diagnosed by echocardiography, such as dystrophinopathies including Duchenne (DMD and Becker (BMD muscular dystrophies, cardiomyopathy of DMD/BMD carriers and X-L dilated cardiomyopathy.

  16. Pattern Dystrophy of the Macula in a Case of Steinert Disease

    Directory of Open Access Journals (Sweden)

    Filipe Esteves

    2013-09-01

    Full Text Available Introduction: Myotonic dystrophies are typically associated with ocular complications like ptosis, weakness of the ocular muscle and cataracts, but also with less recognized retinal changes. Case Report: A 41-year-old female with type 1 myotonic dystrophy complained of progressive vision loss. Slit lamp examination revealed the presence of typical bilateral polychromatic cataract with posterior subcapsular component. Dilated fundus examination was remarkable for bilateral macular depigmented changes. Multimodal imaging analysis of the macula suggested the presence of a butterfly-shaped pattern dystrophy. Discussion: In cases of myotonic dystrophies it is of great relevance to analyze the presence of retinal changes that might limit the visual improvement following cataract extraction.

  17. CT findings of muscular dystrophy

    International Nuclear Information System (INIS)

    Saitoh, Hiroshi

    1991-01-01

    CT scans of muscles in patients with limb girdle type (LG), myotonic type (MYD) and Duchenne type (DMD) dystrophies were obtained at five different body levels: the neck, L3 vertebral body, pelvic girdle, thigh and lower leg. CT numbers, cross sectional areas (CSA) and %CSA of muscle or fat were evaluated in each muscle. The characteristic CT patterns for each type of muscular dystrophy were obtained. Compared with DMD, the gracilis and soleus were more severely damaged in LG and the biceps femoris remained relatively preserved among the hamstrings. In addition, the multifidus of the neck and sternocleidomastoid also were more severely damaged in MYD. This study suggests that CT scan will be useful in the differential diagnosis of these types of muscular dystrophy as well as in planning appropriate rehabilitation and detecting damaged muscles. (author)

  18. The Correlation of Skeletal and Cardiac Muscle Dysfunction in Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Posner, Andrew D; Soslow, Jonathan H; Burnette, W Bryan; Bian, Aihua; Shintani, Ayumi; Sawyer, Douglas B; Markham, Larry W

    2016-01-01

    Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle and cardiac dysfunction. While skeletal muscle dysfunction precedes cardiomyopathy, the relationship between the progressive decline in skeletal and cardiac muscle function is unclear. This relationship is especially important given that the myocardial effects of many developing DMD therapies are largely unknown. Our objective was to assess the relationship between progression of skeletal muscle weakness and onset of cardiac dysfunction in DMD. A total of 77 DMD subjects treated at a single referral center were included. Demographic information, quantitative muscle testing (QMT), subjective muscle strength, cardiac function, and current and retrospective medications were collected. A Spearman rank correlation was used to evaluate for an association between subjective strength and fractional shortening. The effects of total QMT and arm QMT on fractional shortening were examined in generalized least square with and without adjustments for age, ambulatory status, and duration of corticosteroids and cardiac specific medications. We found a significant correlation between maintained subjective skeletal muscle arm and leg strength and maintained cardiac function as defined by fractional shortening (rho=0.47, p=0.004 and rho=0.48, p=0.003, respectively). We also found a significant association between QMT and fractional shortening among non-ambulatory DMD subjects (p=0.03), while this association was not significant in ambulatory subjects. Our findings allow us to conclude that in this population, there exists a significant relationship between skeletal muscle and cardiac function in non-ambulatory DMD patients. While this does not imply a causal relationship, a possible association between skeletal and cardiac muscle function suggests that researchers should carefully monitor cardiac function, even when the primary outcome measures are not cardiac in nature.

  19. [Atypical reaction to anesthesia in Duchenne/Becker muscular dystrophy].

    Science.gov (United States)

    Silva, Helga Cristina Almeida da; Hiray, Marcia; Vainzof, Mariz; Schmidt, Beny; Oliveira, Acary Souza Bulle; Amaral, José Luiz Gomes do

    2017-05-31

    Duchenne/Becker muscular dystrophy affects skeletal muscles and leads to progressive muscle weakness and risk of atypical anesthetic reactions following exposure to succinylcholine or halogenated agents. The aim of this report is to describe the investigation and diagnosis of a patient with Becker muscular dystrophy and review the care required in anesthesia. Male patient, 14 years old, referred for hyperCKemia (chronic increase of serum creatine kinase levels - CK), with CK values of 7,779-29,040IU.L -1 (normal 174IU.L -1 ). He presented with a discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months). He had a history of liver transplantation. In the neurological examination, the patient showed difficulty in walking on one's heels, myopathic sign (hands supported on the thighs to stand), high arched palate, calf hypertrophy, winged scapulae, global muscle hypotonia and arreflexia. Spirometry showed mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted). The in vitro muscle contracture test in response to halothane and caffeine was normal. Muscular dystrophy analysis by Western blot showed reduced dystrophin (20% of normal) for both antibodies (C and N-terminal), allowing the diagnosis of Becker muscular dystrophy. On preanesthetic assessment, the history of delayed motor development, as well as clinical and/or laboratory signs of myopathy, should encourage neurological evaluation, aiming at diagnosing subclinical myopathies and planning the necessary care to prevent anesthetic complications. Duchenne/Becker muscular dystrophy, although it does not increase susceptibility to MH, may lead to atypical fatal reactions in anesthesia. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  20. Intramuscular degeneration process in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Hasegawa, Takeshi; Matsumra, Kiichiro; Hashimoto, Takahiro; Ikehira, Hiroo; Fukuda, Hiroshi; Tateno, Yukio.

    1992-01-01

    Intramuscular degeneration process of Duchenne dystrophy skeletal muscles was investigated by longitudinal skeletal muscle imaging with high-field-strength NMR-CT of 1.5 Tesla. Thigh muscles in 10 cases ranging in age from 4 to 19 years were examined by T 1 -weighted longitudinal images (TR=215∼505 ms, TE=19∼20 ms). The following results were obtained. Skeletal muscle degeneration was depicted as high signal intensity area reflecting its high fat contents. These high signal intensity areas had a longitudinally streaky appearance in parallel direction with myofibers. These findings were more prominent toward myotendon junction than muscle bellies. Skeletal muscle degeneration progressed rapidly between 7 to 10 years of age, and reached a plateau after that. (author)

  1. Natural history of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Qing KE

    2015-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is X-linked recessive hereditary disease. DMD gene mutations result in dystrophin deficiency, which causes not only muscle movement disorders but also scoliosis, cognitive dysfunction, urinary tract diseases, respiratory diseases and heart diseases. Most patients die in early adult for respiratory and circulatory failure. Early multidisciplinary therapies will significantly delay disease progression and improve patients' quality of life. However, DMD diagnosis and treatment exist significantly time delay now. In this study, we review the natural history of DMD, including motor, cognitive, respiratory and heart function, for improving DMD early recognition, diagnosis and treatment, so as to benefit DMD patients. DOI: 10.3969/j.issn.1672-6731.2015.05.004

  2. Myocardial infarction

    International Nuclear Information System (INIS)

    Ando, Jyoji; Yasuda, Hisakazu; Miyamoto, Atsushi; Kobayashi, Tsuyoshi

    1980-01-01

    sup(99m)Tc-pyrophosphate (PYP) scintigraphy and 201 Tl myocardial scintigraphy were utilized for the diagnoses of the presence, the region, and the extent of myocardial infarction. Exercise 201 Tl myocardial scintigrams and exercise radionuclide ventriculography were utilized for diagnosis of coronary artery lesions in angina pectoris. Radionuclide ventriculography was used to investigate effects of coronary artery lesions on cardiac function and hemodynamics. In order to select adequate treatments for myocardial infarction and estimate the prognosis, it was necessary to detect the presence, the region, and the extent of acute myocardial infarction and to investigate effects of partial infarction on hemodynamics by using radionuclide imaging. Exercise myocardial scintigraphy could be carried out noninvasively and repeatedly for diagnosis of coronal artery disease. Therefore, this method could be applied widely. It was possible to use this method as a screening test of coronary artery diseases for the diagnoses of asymptomatic patients who showed ST changes in ECG, the patients with cardiac neurosis and the patency after a reconstructive surgery of coronary artery. (Tsunoda, M.)

  3. Dysphagia in facioscapulohumeral muscular dystrophy.

    NARCIS (Netherlands)

    Wohlgemuth, M.; Swart, B.J.M. de; Kalf, J.G.; Joosten, F.B.M.; Vliet, A.M. van der; Padberg, G.W.A.M.

    2006-01-01

    Dysphagia is not considered a symptom of facioscapulohumeral muscular dystrophy (FSHD). In this study, the authors found that dysphagia does occur in patients with advanced FSHD showing mild involvement of the jaw and lingual muscles. Dysphagia is seldom life threatening in these patients. The

  4. AMPUTATION AND REFLEX SYMPATHETIC DYSTROPHY

    NARCIS (Netherlands)

    GEERTZEN, JHB; EISMA, WH

    Reflex sympathetic dystrophy is a chronic pain syndrome characterized by chronic burning pain, restricted range of motion, oedema and vasolability. Patients are difficult to treat and the prognosis is very often poor. This report emphasizes that an amputation in case of a reflex sympathetic

  5. Glucocorticoids for Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-07-01

    Full Text Available Investigators at the Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, and other centers in the UK, conducted a prospective longitudinal study across 17 neuromuscular centers in the UK of 360 boys aged 3-15 years with Duchenne muscular dystrophy who were treated with daily or intermittent (10 days on/10 days off prednisolone for a mean duration of 4 years.

  6. Prednisone Therapy for Duchenne Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-02-01

    Full Text Available The effects of prednisone on muscle function and the extent of steroid-related adverse effects were studied in 17 ambulant children with Duchenne muscular dystrophy (DMD at University Hospital, Groningen; Rehabilitation Centre, Utrecht; and Leiden University Medical Centre, the Netherlands.

  7. Faecal incontinence in myotonic dystrophy

    OpenAIRE

    Abercrombie, J; Rogers, J; Swash, M

    1998-01-01

    Two siblings with myotonic dystrophy presented for treatment of faecal incontinence. The pathophysiology of this functional disorder is described with the results of anorectal manometry, EMG, and biopsy of smooth and striated muscle of the anorectal sphincters. Both medical and surgical management of the incontinence was unsatisfactory in the long term. Involvement of gastrointestinal musculature is a characteristic feature the disease.



  8. Inherited myopathies and muscular dystrophies

    NARCIS (Netherlands)

    Cardamone, Michael; Darras, Basil T.; Ryan, Monique M.

    The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases presenting with common complaints and physical signs: weakness, motor delay, and respiratory and bulbar dysfunction. The myopathies are caused by genetic defects in the contractile apparatus of muscle, and

  9. Repair of an inguinoscrotal hernia in a patient with Becker muscular dystrophy.

    Science.gov (United States)

    Tatulli, F; Caraglia, A; Delcuratolo, A; Cassano, S; Chetta, G S

    2017-01-01

    Inguinal hernia repairs are routinely performed as outpatient procedures in most patients, whereas a few require admission due to clinical or social peculiarities. Muscular dystrophies are inherited disorders characterized by progressive muscle wasting and weakness. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards a 48 y. o. male patient diagnosed with Becker Muscular Dystrophy by muscle biopsy 10 years earlier. He had a left-sided sizable inguinoscrotal hernia with repeat episodes of incarceration. An elective mesh repair with suction drainage was accomplished under selective spinal anesthesia. The post-operative course was uneventful. A few inguinal hernia repairs require admission due to peculiarities such as extensive scrotal hernias requiring suction drainage. Muscular dystrophies are inherited disorders with no cure and no two dystrophy patients are exactly alike, therefore the health issues will be different for each individual. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards the successful elective mesh repair with suction drainage of a large left-sided inguino-scrotal hernia in a 48 y. o. male patient affected by Becker muscular dystrophy by selective spinal anesthesia obtained by 10 milligrams of hyperbaric bupivacaine. Effective mesh repair with suction drainage of large inguinal hernias under spinal anesthesia can be achieved in patients affected by muscular dystrophy.

  10. Oxidative stress and pathology in muscular dystrophies: focus on protein thiol oxidation and dysferlinopathies.

    Science.gov (United States)

    Terrill, Jessica R; Radley-Crabb, Hannah G; Iwasaki, Tomohito; Lemckert, Frances A; Arthur, Peter G; Grounds, Miranda D

    2013-09-01

    The muscular dystrophies comprise more than 30 clinical disorders that are characterized by progressive skeletal muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for pathogenesis generally remains unknown. It is considered that disturbed levels of reactive oxygen species (ROS) contribute to the pathology of many muscular dystrophies. Reactive oxygen species and oxidative stress may cause cellular damage by directly and irreversibly damaging macromolecules such as proteins, membrane lipids and DNA; another major cellular consequence of reactive oxygen species is the reversible modification of protein thiol side chains that may affect many aspects of molecular function. Irreversible oxidative damage of protein and lipids has been widely studied in Duchenne muscular dystrophy, and we have recently identified increased protein thiol oxidation in dystrophic muscles of the mdx mouse model for Duchenne muscular dystrophy. This review evaluates the role of elevated oxidative stress in Duchenne muscular dystrophy and other forms of muscular dystrophies, and presents new data that show significantly increased protein thiol oxidation and high levels of lipofuscin (a measure of cumulative oxidative damage) in dysferlin-deficient muscles of A/J mice at various ages. The significance of this elevated oxidative stress and high levels of reversible thiol oxidation, but minimal myofibre necrosis, is discussed in the context of the disease mechanism for dysferlinopathies, and compared with the situation for dystrophin-deficient mdx mice. © 2013 The Authors Journal compilation © 2013 FEBS.

  11. Autonomic Dysfunction in Muscular Dystrophy: A Theoretical Framework for Muscle Reflex Involvement

    Directory of Open Access Journals (Sweden)

    Scott Alan Smith

    2014-02-01

    Full Text Available Muscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy.

  12. Progress in CRISPR/Cas9 system and its application in Duchenne's muscular dystrophy%成簇规律间隔的短回文重复序列/Cas9及在Duchenne型肌营养不良中应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    李文彬

    2017-01-01

    The CRISPR/Cas9 is an adaptive immune system which exists in bacteria and archaea,providing bacteria and archaea to resist against infection of phage.Cas9 can target and degrade exogenous DNA by RNA's guiding,also provide gene over expression,stereotactical block,and high-throughput screening after modifying to broaden its application.The newly discovered CRISPR/C2c2 can target and degrade exogenous RNA,and has more specificity and efficiency than RNA interference.The CRISPR/Cas9 system has been applied to modify the dystrophin gene in Duchenne's muscular dystrophy mice models,maintaining the expression of dystrophin persistent and restoring the muscle power,with no adverse reactions on brain and germline,which provides a new direction for the treatment of Duchenne's muscular dystrophy.This paper reviews the research progress of CRISPR/Cas9 and its application in Duchenne's muscular dystrophy.%成簇规律间隔的短回文重复序列(clustered regularly interspaced short palindromic repeats,CRISPR)/Cas9存在于细菌和古细菌中,是细菌抵抗噬菌体入侵的适应性免疫系统,可通过向导RNA靶向外源性DNA并对其进行剪切,还可经修饰后进行基因的过表达、阻断以及高通量筛选,扩大了CRISPR系统的应用范围.新近发现的CRISPR/C2c2系统可靶向降解外源性RNA,在特异性及效率上较RNA干扰(RNA interference,RNAi)技术更有优势.应用CRISPR/Cas9系统修正小鼠抗肌萎缩蛋白,可使抗肌萎缩蛋白表达持久,肌力恢复良好,且无明显脑部及生殖系统不良反应,为Duchenne型肌营养不良提供了新的治疗方向.本文就CRISPR/Cas9及其在Duchenne型肌营养不良中应用的研究进展作一综述.

  13. Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Goyenvalle Aurélie

    2011-02-01

    Full Text Available Abstract Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues.

  14. Neuroaxonal Dystrophy and Cavitating Leukoencephalopathy of Chihuahua Dogs.

    Science.gov (United States)

    Degl'Innocenti, Sara; Asiag, Nimrod; Zeira, Offer; Falzone, Cristian; Cantile, Carlo

    2017-09-01

    A novel form of neuroaxonal dystrophy is described in 3 Chihuahua pups, 2 of which were from the same litter. It was characterized not only by accumulation of numerous and widely distributed axonal swellings (spheroids) but also by a severe cavitating leukoencephalopathy. The dogs presented with progressive neurological signs, including gait abnormalities and postural reaction deficits. Magnetic resonance images and gross examination at necropsy revealed dilation of lateral ventricles and cerebral atrophy, accompanied by cavitation of the subcortical white matter. Histopathologically, severe axonal degeneration with formation of large spheroids was found in the cerebral and cerebellar white matter, thalamus, and brainstem nuclei. Small-caliber spheroids were observed in the cerebral and cerebellar gray matter. The telencephalic white matter had severe myelin loss and cavitation with relative sparing of the U-fibers. Different from previously reported cases of canine neuroaxonal dystrophy, in these Chihuahuas the spheroid distribution predominantly involved the white matter with secondary severe leukoencephalopathy.

  15. An Overview of Recent Therapeutics Advances for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Mah, Jean K

    2018-01-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. Mutations of the DMD gene destabilize the dystrophin associated glycoprotein complex in the sarcolemma. Ongoing mechanical stress leads to unregulated influx of calcium ions into the sarcoplasm, with activation of proteases, release of proinflammatory cytokines, and mitochondrial dysfunction. Cumulative damage and reparative failure leads to progressive muscle necrosis, fibrosis, and fatty replacement. Although there is presently no cure for DMD, scientific advances have led to many potential disease-modifying treatments, including dystrophin replacement therapies, upregulation of compensatory proteins, anti-inflammatory agents, and other cellular targets. Recently approved therapies include ataluren for stop codon read-through and eteplirsen for exon 51 skipping of eligible individuals. The purpose of this chapter is to summarize the clinical features of DMD, to describe current outcome measures used in clinical studies, and to highlight new emerging therapies for affected individuals.

  16. The new frontier in muscular dystrophy research: booster genes

    DEFF Research Database (Denmark)

    Engvall, Eva; Wewer, Ulla M

    2003-01-01

    More than 30 different forms of muscular dystrophy (MD) have been molecularly characterized and can be diagnosed, but progress toward treatment has been slow. Gene replacement therapy has met with great difficulty because of the large size of the defective genes and because of difficulties...... of the boosters are better understood, drugs may be developed to provide the boost to muscle. Some of the experiences in models of muscular dystrophy may inspire new approaches in other genetic degenerative diseases as well....... in delivering a gene to all muscle groups. Cell replacement therapy has also been difficult to realize. Will it even be possible to design specific therapy protocols for all MDs? Or is a more realistic goal to treat some of the secondary manifestations that are common to several forms of MD, such as membrane...

  17. Myocardial scintigraphy

    International Nuclear Information System (INIS)

    Bunko, Hisashi; Hisada, Kinichi

    1982-01-01

    Among the various methods of image diagnosis of the cardiovascular disorder, nuclear cardiology provides noninvasive means for evaluation of myocardial perfusion as well as morphological and functional informations. In this article, clinical application and image diagnosis of myocardial scintigraphy including Tl-201 myocardial perfusion scintigraphy, single photon emission computed tomography with Tl-201, acute myocardial infarction scintigraphy with Tc-99m-pyrophosphate and Ga-67 imaging of the heart, were discussed. Multiplanar imaging of the heart with Tl-201 after stress and at redistribution was the accepted method for detection and evaluation of the ischemic heart disease. Although it achieved high sensitivity and specificity for ischemic heart disease, detection of the small ischemia and quantation of the regional Tl-201 accumulation were difficult with conventional multiplanar imaging. Application of emission computed tomography improved detectability and quantitativity of the ischemia. However, 7-pinhole tomography did not increase the diagnostic accuracy significantly. It had limited clinical applicability due to poor quantitativity in spite of improved image contrast and its tomographic nature. Advantage and limitation of these tomographic imaging and multiplanar imaging were discussed. Problems and prognostic significance of pyrophosphate imaging of the acute myocardial infarction were also discussed. Visualization of the heart with Ga-67 was helpful for identification of the tumor or inflammation of the heart as well as evaluation of the effect of the therapy. (author)

  18. Infrastructure for Clinical Trials in Duchenne Dystrophy

    Science.gov (United States)

    2010-09-13

    A Zimmerman, T Duong, J Florence and the CINRG Investigators. Pulmonary Function Characteristics of Boys with Duchenne and Becker Muscular Dystrophy ...designated CINRG site staff 1. Has the participant been clinically diagnosed with Limb-Girdle or Becker muscular dystrophy ? LGMD BMD 2. Was...Number: W81XWH-09-1-0592 TITLE: CINRG: Infrastructure for Clinical Trials in Duchenne Dystrophy PRINCIPAL INVESTIGATOR: Avital Cnaan, PhD

  19. [Encopresis revealing myotonic dystrophy in 2 children].

    Science.gov (United States)

    Avez-Couturier, J; Michaud, L; Cuisset, J-M; Lamblin, M-D; Dolhem, P; Turck, D; Vallée, L; Gottrand, F

    2009-05-01

    Gastrointestinal symptoms are very frequent in myotonic dystrophy but largely unrecognized. They can be the revealing factors of the disease. We report 2 cases of 10 and 17-year-old children with persistent encopresis starting at the age of 3 and 5 years in spite of laxative treatment. Neurological examination and anorectal manometry provided the diagnosis of myotonic dystrophy. Procainamide treatment was introduced and the digestive symptoms improved. Any child with encopresis should have complete evaluation to rule out the diagnosis of myotonic dystrophy and physicians should look for upper and/or lower gastrointestinal symptoms in every patient with myotonic dystrophy.

  20. Radionuclide study for cardiac lesion in Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Oguni, Hirokazu; Osawa, Makiko; Shishikura, Keiko

    1985-12-01

    Tl-201 myocardial scintigraphy and radionuclide ventriculography with Tc-99m were performed in 10 patients with Duchenne muscular dystropohy (DMD) and 2 siblings with Becker muscular dystrophy (BMD). Perfusion defect especially in the left ventricular posterolateral wall (LVPLW) and cardiac apex was seen on Tl-201 imaging in 6 of the DMD patients and one of the BMD patients. For these patients, Tc-99m imaging also showed left ventricular local wall motion abnormality in 5 patients and a decreased left ventricular ejection fraction in 4 patients. These findings coincided well with fibrosis of the LVPLW found on autopsy. There were individual differences regarding the occurrence of cardiac complications. One of the BMD patients, as well as DMD patients, had also cardiac complications which have long been considered less common. (Namekawa, K.).

  1. Radionuclide study for cardiac lesion in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Oguni, Hirokazu; Osawa, Makiko; Shishikura, Keiko

    1985-01-01

    Tl-201 myocardial scintigraphy and radionuclide ventriculography with Tc-99m were performed in 10 patients with Duchenne muscular dystropohy (DMD) and 2 siblings with Becker muscular dystrophy (BMD). Perfusion defect especially in the left ventricular posterolateral wall (LVPLW) and cardiac apex was seen on Tl-201 imaging in 6 of the DMD patients and one of the BMD patients. For these patients, Tc-99m imaging also showed left ventricular local wall motion abnormality in 5 patients and a decreased left ventricular ejection fraction in 4 patients. These findings coincided well with fibrosis of the LVPLW found on autopsy. There were individual differences regarding the occurrence of cardiac complications. One of the BMD patients, as well as DMD patients, had also cardiac complications which have long been considered less common. (Namekawa, K.)

  2. Secondary Conditions Among Males With Duchenne or Becker Muscular Dystrophy.

    Science.gov (United States)

    Latimer, Rebecca; Street, Natalie; Conway, Kristin Caspers; James, Kathy; Cunniff, Christopher; Oleszek, Joyce; Fox, Deborah; Ciafaloni, Emma; Westfield, Christina; Paramsothy, Pangaja

    2017-06-01

    Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred nine caregivers of affected males (aged 3-31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The 5 most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones were found among nonambulatory males compared to ambulatory males. Attention-deficit hyperactivity disorder (ADHD) was more common in ambulatory than nonambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis.

  3. Emerging genetic therapies to treat Duchenne muscular dystrophy

    Science.gov (United States)

    Nelson, Stanley F.; Crosbie, Rachelle H.; Miceli, M. Carrie; Spencer, Melissa J.

    2010-01-01

    Purpose of review Duchenne muscular dystrophy is a progressive muscle degenerative disease caused by dystrophin mutations. The purpose of this review is to highlight two emerging therapies designed to repair the primary genetic defect, called `exon skipping' and `nonsense codon suppression'. Recent findings A drug, PTC124, was identified that suppresses nonsense codon translation termination. PTC124 can lead to restoration of some dystrophin expression in human Duchenne muscular dystrophy muscles with mutations resulting in premature stops. Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the exclusion of exon 51 from mature mRNA. They can restore the translational reading frame to dystrophin transcripts from patients with a particular subset of dystrophin gene deletions and lead to some restoration of dystrophin expression in affected boys' muscle in vivo. Both approaches have concluded phase I trials with no serious adverse events. Summary These novel therapies that act to correct the primary genetic defect of dystrophin deficiency are among the first generation of therapies tailored to correct specific mutations in humans. Thus, they represent paradigm forming approaches to personalized medicine with the potential to lead to life changing treatment for those affected by Duchenne muscular dystrophy. PMID:19745732

  4. Altered cross-bridge properties in skeletal muscle dystrophies

    Directory of Open Access Journals (Sweden)

    Aziz eGuellich

    2014-10-01

    Full Text Available Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca2+ through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal muscle dystrophies and discuss their ultimate impacts on striated muscle function.

  5. Composite biomarkers for assessing Duchenne muscular dystrophy: an initial assessment.

    Science.gov (United States)

    Shklyar, Irina; Pasternak, Amy; Kapur, Kush; Darras, Basil T; Rutkove, Seward B

    2015-02-01

    Compared with individual parameters, composite biomarkers may provide a more effective means for monitoring disease progression and the effects of therapy in clinical trials than single measures. In this study, we built composite biomarkers for use in Duchenne muscular dystrophy by combining values from two objective measures of disease severity: electrical impedance myography and quantitative ultrasound and evaluating how well they correlated to standard functional measures. Using data from an ongoing study of electrical impedance myography and quantitative ultrasound in 31 Duchenne muscular dystrophy and 26 healthy boys aged 2-14 years, we combined data sets by first creating z scores based on the normal subject data and then using simple mathematical operations (addition and multiplication) to create composite measures. These composite scores were then correlated to age and standard measures of function including the 6-minute walk test, the North Star Ambulatory Assessment, and handheld dynamometry. Combining data sets resulted in stronger correlations with all four outcomes than for either electrical impedance myography or quantitative ultrasound alone in six of eight instances. These improvements reached statistical significance (P Duchenne muscular dystrophy clinical trials is warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Recent achievements in restorative neurology: Progressive neuromuscular diseases

    International Nuclear Information System (INIS)

    Dimitrijevic, M.R.; Kakulas, B.A.; Vrbova, G.

    1986-01-01

    This book contains 27 chapters. Some of the chapter titles are: Computed Tomography of Muscles in Neuromuscular Disease; Mapping the Genes for Muscular Dystrophy; Trophic Factors and Motor Neuron Development; Size of Motor Units and Firing Rate in Muscular Dystrophy; Restorative Possibilities in Relation to the Pathology of Progressive Neuromuscular Disease; and An Approach to the Pathogenesis of some Congenital Myopathies

  7. Body weight-supported training in Becker and Limb Girdle 2I muscular dystrophy

    DEFF Research Database (Denmark)

    Jensen, Bente Rona; Berthelsen, Martin Peter; Husu, Edith

    2016-01-01

    INTRODUCTION: We studied the functional effects of combined strength and aerobic anti-gravity training in severely affected patients with Becker and Limb-Girdle muscular dystrophies. METHODS: Eight patients performed 10-week progressive combined strength (squats, calf raises, lunges) and aerobic...

  8. Improving the Reading Skills of Young People with Duchenne Muscular Dystrophy in Preparation for Adulthood

    Science.gov (United States)

    Hoskin, Janet; Fawcett, Angela

    2014-01-01

    Duchenne muscular dystrophy (DMD) is a progressive genetic condition that affects both muscle and brain. Children with DMD are at risk of psycho-social difficulties such as poor academic achievement and behavioural and socio-emotional problems. This article by Janet Hoskin and Angela Fawcett, both from the University of Swansea, describes how 34…

  9. The influence of low dystrophin levels on disease pathology in mouse models for Duchenne Muscular Dystrophy

    NARCIS (Netherlands)

    Putten, Maaike van

    2013-01-01

    Duchenne muscular dystrophy (DMD) is the most prevalent neuromuscular disorder, caused by mutations in the DMD gene that prevent synthesis of dystrophin. Fibers that lack dystrophin are sensitive to exercise-induced damage, resulting in progressive muscle wasting, loss of ambulation and premature

  10. Some Dynamics of Personality Development in Boys Suffering from Muscular Dystrophy

    Science.gov (United States)

    Mearig, Judith S.

    1973-01-01

    Discussed are personality aspects of Duchenne or pseudohypertrophic muscular dystrophy, a progressive wasting of muscular tissue, which afflicts only boys, and usually has its noticeable onset before the age of 6 years; and described is the development of three male dystrophic siblings. (DB)

  11. Investigation of Poor Academic Achievement in Children with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Hinton, V. J.; De Vivo, D. C.; Fee, R.; Goldstein, E.; Stern, Y.

    2004-01-01

    Duchenne Muscular Dystrophy (DMD) is a neurogenetic developmental disorder that presents with progressive muscular weakness. It is caused by a mutation in a gene that results in the absence of specific products that normally localize to muscle cells and the central nervous system (CNS). The majority of affected individuals have IQs within the…

  12. Becker muscular dystrophy: an unusual presentation.

    OpenAIRE

    Thakker, P B; Sharma, A

    1993-01-01

    A 15 year old boy who presented with passing painless dark urine was found to have myoglobinuria. His creatine phosphokinase was raised, and a muscle biopsy specimen showed non-specific dystrophic changes. Subsequent DNA analysis led to the diagnosis of Becker muscular dystrophy. Myoglobinuria may be a presenting symptom of Becker muscular dystrophy.

  13. Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction--angiographic and intravascular ultrasound--results from the TErapia Celular Aplicada al Miocardio Pilot study.

    Science.gov (United States)

    Arnold, Roman; Villa, Adolfo; Gutiérrez, Hipólito; Sánchez, Pedro L; Gimeno, Federico; Fernández, Maria E; Gutiérrez, Oliver; Mota, Pedro; Sánchez, Ana; García-Frade, Javier; Fernández-Avilés, Francisco; San Román, Jose A

    2010-06-01

    We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy. Copyright 2010 Mosby, Inc. All rights reserved.

  14. Fat embolism after fractures in Duchenne muscular dystrophy: an underdiagnosed complication? A systematic review

    Directory of Open Access Journals (Sweden)

    Feder D

    2017-10-01

    Full Text Available David Feder,1 Miriam Eva Koch,1 Beniamino Palmieri,2 Fernando Luiz Affonso Fonseca,1 Alzira Alves de Siqueira Carvalho3 1Pharmacology Department, Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil; 2Department of General Surgery and Surgical Specialties, University of Modena and Reggio Emilia Medical School, Surgical Clinic, Modena, Italy; 3Neuroscience Department, Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil Abstract: Duchenne muscular dystrophy is the most frequent lethal genetic disease. Several clinical trials have established both the beneficial effect of steroids in Duchenne muscular dystrophy and the well-known risk of side effects associated with their daily use. For many years it has been known that steroids associated with ambulation loss lead to obesity and also damage the bone structure resulting in the bone density reduction and increased incidence of bone fractures and fat embolism syndrome, an underdiagnosed complication after fractures. Fat embolism syndrome is characterized by consciousness disturbance, respiratory failure and skin rashes. The use of steroids in Duchenne muscular dystrophy may result in vertebral fractures, even without previous trauma. Approximately 25% of patients with Duchenne muscular dystrophy have a long bone fracture, and 1% to 22% of fractures have a chance to develop fat embolism syndrome. As the patients with Duchenne muscular dystrophy have progressive cardiac and respiratory muscle dysfunction, the fat embolism may be unnoticed clinically and may result in increased risk of death and major complications. Different treatments and prevention measures of fat embolism have been proposed; however, so far, there is no efficient therapy. The prevention, early diagnosis and adequate symptomatic treatment are of paramount importance. The fat embolism syndrome should always be considered in patients with Duchenne muscular dystrophy presenting with fractures, or an unexplained and

  15. At the Crossroads of Clinical and Preclinical Research for Muscular Dystrophy-Are We Closer to Effective Treatment for Patients?

    Science.gov (United States)

    Gawlik, Kinga I

    2018-05-16

    Among diseases affecting skeletal muscle, muscular dystrophy is one of the most devastating and complex disorders. The term 'muscular dystrophy' refers to a heterogeneous group of genetic diseases associated with a primary muscle defect that leads to progressive muscle wasting and consequent loss of muscle function. Muscular dystrophies are accompanied by numerous clinical complications and abnormalities in other tissues that cause extreme discomfort in everyday life. The fact that muscular dystrophy often takes its toll on babies and small children, and that many patients die at a young age, adds to the cruel character of the disease. Clinicians all over the world are facing the same problem: they have no therapy to offer except for symptom-relieving interventions. Patients, their families, but also clinicians, are in urgent need of an effective cure. Despite advances in genetics, increased understanding of molecular mechanisms underlying muscle disease, despite a sweeping range of successful preclinical strategies and relative progress of their implementation in the clinic, therapy for patients is currently out of reach. Only a greater comprehension of disease mechanisms, new preclinical studies, development of novel technologies, and tight collaboration between scientists and physicians can help improve clinical treatment. Fortunately, inventiveness in research is rapidly extending the limits and setting new standards for treatment design. This review provides a synopsis of muscular dystrophy and considers the steps of preclinical and clinical research that are taking the muscular dystrophy community towards the fundamental goal of combating the traumatic disease.

  16. Prevalence of generalized retinal dystrophy in Denmark

    DEFF Research Database (Denmark)

    Bertelsen, Mette; Jensen, Hanne; Bregnhøj, Jesper F

    2014-01-01

    of this study was to examine the prevalence and diagnostic spectrum of generalized retinal dystrophy in the Danish population. METHODS: A population-based cross-sectional study with data from the Danish Retinitis Pigmentosa Registry that comprises all patients in Denmark with generalized retinal......PURPOSE: Generalized retinal dystrophy is a frequent cause of visual impairment and blindness in younger individuals and a subject of new clinical intervention trials. Nonetheless, there are few nation-wide population-based epidemiological data of generalized retinal dystrophy. The purpose...... and chorioretinal dystrophies from the 19th century to the present. Among 3076 registered cases, the primary diagnosis of generalized retinal dystrophy was assessed by chart review, including fundus photographs and electroretinograms. Demographic data on the Danish population were retrieved from Statistics Denmark...

  17. Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2

    DEFF Research Database (Denmark)

    Witting, Nanna; Duno, M; Vissing, J

    2013-01-01

    Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic......, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest...

  18. Cognitive behaviour therapy plus aerobic exercise training to increase activity in patients with myotonic dystrophy type 1 (DM1) compared to usual care (OPTIMISTIC): study protocol for randomised controlled trial

    NARCIS (Netherlands)

    van Engelen, Baziel; Abghari, Shaghayegh; Aschrafi, Armaz; Bouman, Sacha; Cornelissen, Yvonne; Glennon, Jeffrey; Groot, Perry; Heerschap, Arend; Heskamp, Linda; Heskes, Tom; Kapusta, Katarzyna; Klerks, Ellen; Knoop, Hans; Maas, Daphne; Okkersen, Kees; Poelmans, Geert; Rahmadi, Ridho; van Nimwegen, Marlies; Gorman, Grainne; Moreno, Cecilia Jimenez; Lochmüller, Hanns; Trenell, Mike; van Laar, Sandra; Wood, Libby; Schoser, Benedikt; Wenninger, Stephan; Schüller, Angela; Auguston, Mrs Rémie; Baptiste, Lignier; Barau, Caroline; Bassez, Guillaume; Chevalier, Pascale; Couppey, Florence; Delmas, Stéphanie; Deux, Jean-François; Dogan, Celine; Hamadouche, Amira; Hankiewicz, Karolina; Lhermet, Laure; Minier, Lisa; Rialland, Amandine; Schmitz, David; Monckton, Darren G.; Cumming, Sarah A.; Adam, Berit; Donnan, Peter; Hannah, Michael; Hogarth, Fiona; Littleford, Roberta; McKenzie, Emma

    2015-01-01

    Background: Myotonic dystrophy type 1 (DM1) is a rare, inherited chronic progressive disease as well as an autosomal dominant multi-systemic disorder. It is probably one of the most common adult forms of muscular dystrophy, with a prevalence of approximately 10 per 100,000 people affected. With 733

  19. Cognitive behaviour therapy plus aerobic exercise training to increase activity in patients with myotonic dystrophy type 1 (DM1) compared to usual care (OPTIMISTIC): study protocol for randomised controlled trial

    NARCIS (Netherlands)

    Engelen, B.G.M. van; Groot, P.C.; Abghari, S.; Aschrafi, A.; Bouman, S.F.; Cornelissen, Y.; Glennon, J.C.; Heerschap, A.; Heskamp, L.; Heskes, T.M.; Kapusta, K.A.; Klerks, E.; Knoop, H.; Maas, D; Okkersen, C.P.; Poelmans, G.J.V.; Rahmadi, R.; Nimwegen, M. van; et al.,

    2015-01-01

    BACKGROUND: Myotonic dystrophy type 1 (DM1) is a rare, inherited chronic progressive disease as well as an autosomal dominant multi-systemic disorder. It is probably one of the most common adult forms of muscular dystrophy, with a prevalence of approximately 10 per 100,000 people affected. With 733

  20. Late-onset Becker-type muscular dystrophy in a Border terrier dog.

    Science.gov (United States)

    Jeandel, A; Garosi, L S; Davies, L; Guo, L T; Salgüero, R; Shelton, G D

    2018-01-29

    A 9-year-old Border terrier was presented to a referral hospital after a 1-year history of progressive stiffness and exercise intolerance. Neurological examination was consistent with a neuromuscular disorder. Serum creatine kinase activity was mildly elevated. A myopathy was suspected based on MRI findings and electrophysiological examination. Muscle histopathology was consistent with a severe non-inflammatory myopathy of a dystrophic type. Immunofluorescence and western blotting confirmed a dystrophinopathy with an 80-kDa truncated dystrophin fragment similar to Becker muscular dystrophy in people. To our knowledge, this is the first description of a late-onset Becker-type muscular dystrophy in a dog, and the first description of a dystrophinopathy in a Border terrier. Muscular dystrophy in dogs should not be ruled out based on late onset clinical signs and only mildly elevated creatine kinase. © 2018 British Small Animal Veterinary Association.

  1. Sparks, signals and shock absorbers: how dystrophin loss causes muscular dystrophy.

    Science.gov (United States)

    Batchelor, Clare L; Winder, Steve J

    2006-04-01

    The dystrophin-glycoprotein complex (DGC) can be considered as a specialized adhesion complex, linking the extracellular matrix to the actin cytoskeleton, primarily in muscle cells. Mutations in several components of the DGC lead to its partial or total loss, resulting in various forms of muscular dystrophy. These typically manifest as progressive wasting diseases with loss of muscle integrity. Debate is ongoing about the precise function of the DGC: initially a strictly mechanical role was proposed but it has been suggested that there is aberrant calcium handling in muscular dystrophy and, more recently, changes in MAP kinase and GTPase signalling have been implicated in the aetiology of the disease. Here, we discuss new and interesting developments in these aspects of DGC function and attempt to rationalize the mechanical, calcium and signalling hypotheses to provide a unifying hypothesis of the underlying process of muscular dystrophy.

  2. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

    Science.gov (United States)

    Marshall, Jamie L.; Kwok, Yukwah; McMorran, Brian; Baum, Linda G.; Crosbie-Watson, Rachelle H.

    2013-01-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important therapeutic target. Here, we review current protein replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. PMID:23601082

  3. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.

    Science.gov (United States)

    Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J; Baum, Linda G; Crosbie-Watson, Rachelle H

    2013-09-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. © 2013 FEBS.

  4. Magnetic resonance imaging of children with Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Schreiber, A.; Smith, W.L.; Franken, E.A.; Dunn, V.; Ehrhardt, J.; Ionasescu, V.; Zellweger, H.

    1987-10-01

    Eight children representing a spectrum of clinical states of biopsy-proven Duchenne muscular dystrophy (DMD) underwent magnetic resonance (MR) scans to assess the degree of muscular involvement and disease progression. Five muscle groups (neck, shoulder girdle, pelvic girdle, thigh and calf) were evaluated. In each case, involved muscles were clearly demarcated. Image estimates of disease severity by degree of muscle involvement correlated well with clinical staging. In our experience MR is useful for assessment of disease stage, selection of appropriate muscles for biopsy and planning for courses of physical and rehabilitation therapy.

  5. Magnetic resonance imaging of children with Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Schreiber, A.; Smith, W.L.; Franken, E.A.; Dunn, V.; Ehrhardt, J.; Ionasescu, V.; Zellweger, H.

    1987-01-01

    Eight children representing a spectrum of clinical states of biopsy-proven Duchenne muscular dystrophy (DMD) underwent magnetic resonance (MR) scans to assess the degree of muscular involvement and disease progression. Five muscle groups (neck, shoulder girdle, pelvic girdle, thigh and calf) were evaluated. In each case, involved muscles were clearly demarcated. Image estimates of disease severity by degree of muscle involvement correlated well with clinical staging. In our experience MR is useful for assessment of disease stage, selection of appropriate muscles for biopsy and planning for courses of physical and rehabilitation therapy. (orig.)

  6. Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Melinda F. Davis

    2010-10-01

    Full Text Available Medical investigations use a wide variety of outcome indicators that are often not comparable. It can be challenging to integrate results across multiple studies that do not share a common metric. Some conditions such as Duchenne and Becker muscular dystrophy have a predictable course of disease progression. Severity can be inferred from a patient's medical history. This paper describes the development of a disease severity measure using common markers of disease progression. Rasch modeling was used to estimate severity using dichotomous events that indicate disease progression. Caregivers of 34 young men with Duchenne or Becker muscular dystrophy completed structured interviews about their care and medical history. Interview questions included surgeries (tendon release, scoliosis, tracheostomy, respiratory equipment (assisted ventilation, cough assist devices, and the use of other medical equipment (e.g., braces, walkers, wheelchairs, transfer boards, hospital beds. The resulting measure had a reliability of .83. The correlation between the severity measure and the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS was .68. Preliminary results and item calibrations are provided for the severity measure that can be estimated from caregiver reports or administrative data. DOI: 10.2458/azu_jmmss.v1i1.76

  7. Phenotypic variability in Meesmann's dystrophy

    DEFF Research Database (Denmark)

    Ehlers, Niels; Hjortdal, Jesper; Nielsen, Kim

    2008-01-01

    symptoms often include blurred vision and ocular irritation. Typical cases may be entirely free of complaints. Intermittent pain episodes, such as occur in recurrent erosion syndrome, are not the rule. Genetic sequencing indicated a familial relationship with the originally described Meesmann family......'s dystrophy occurs worldwide. The largest family described is the original German one, now supplemented with a Danish branch. Despite the presence of an identical genetic defect, the clinical phenotype varies. This suggests that non-KRT12-related mechanisms are responsible for the variation....

  8. Optimizing Bone Health in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Jason L. Buckner

    2015-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA, as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

  9. Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Hermans Mieke CE

    2012-07-01

    Full Text Available Abstract Background Myotonic dystrophy type 1 (MD1 is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1. Methods Eighty MD1 patients underwent physical examination, electrocardiography (ECG, echocardiography and cardiovascular magnetic resonance (CMR. Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length. Results Functional and structural abnormalities were detected in 35 patients (44%. Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%. In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04, male gender (p Conclusions CMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration.

  10. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    Science.gov (United States)

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  11. Non-Coding RNAs in Muscle Dystrophies

    Directory of Open Access Journals (Sweden)

    Alessandra Ferlini

    2013-09-01

    Full Text Available ncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and development of novel therapeutic approaches. Important data come from the field of hereditary muscle dystrophies, like Duchenne muscle dystrophy and Myotonic dystrophies, rare diseases affecting 1 in 7000–15,000 newborns and is characterized by severe to mild muscle weakness associated with cardiac involvement. Novel therapeutic approaches are now ongoing for these diseases, also based on splicing modulation. In this review we provide an overview about ncRNAs and their behavior in muscular dystrophy and explore their links with diagnosis, prognosis and treatments, highlighting the role of regulatory RNAs in these pathologies.

  12. Physical Therapy and Facioscapulohumeral Muscular Dystrophy (FSHD)

    Science.gov (United States)

    Physical Therapy & FSHD Facioscapulohumeral Muscular Dystrophy A Guide for Patients & Physical Therapists Authors: Wendy M. King, P.T., Assistant ... Shree Pandya, P.T., M.S., Assistant Professor, Neurology & Physical Medicine and Rehabilitation A publication of the FSH ...

  13. 3-Methylhistidine excretion in myotonic dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Griggs, R.C.; Moxley, R.T. III; Forbes, G.B.

    1980-12-01

    3-Methylhistidine (3-MH) excretion reflects the rate of muscle protein catabolism, since 3-MH occurs almost exclusively in muscle actin and myosin and is not reutilized or catabolized. We studied 3-MH excretion in 9 patients with myotonic dystrophy, 8 normals, and 10 disease controls with Duchenne dystrophy and other disorders. 3-MH excretion was expressed relative to muscle mass as determined by both urinary creatinine and total body potassium (/sup 40/K method). Absolute 3-MH excretion was decreased in myotonic dystrophy patients but was normal when related to muscle mass. The finding of normal 3-MH excretion in myotonic dystrophy suggests that the muscle wasting in this disorder results from impaired anabolic processes rather than accelerated muscle destruction.

  14. 3-Methylhistidine excretion in myotonic dystrophy

    International Nuclear Information System (INIS)

    Griggs, R.C.; Moxley, R.T. III; Forbes, G.B.

    1980-01-01

    3-Methylhistidine (3-MH) excretion reflects the rate of muscle protein catabolism, since 3-MH occurs almost exclusively in muscle actin and myosin and is not reutilized or catabolized. We studied 3-MH excretion in 9 patients with myotonic dystrophy, 8 normals, and 10 disease controls with Duchenne dystrophy and other disorders. 3-MH excretion was expressed relative to muscle mass as determined by both urinary creatinine and total body potassium ( 40 K method). Absolute 3-MH excretion was decreased in myotonic dystrophy patients but was normal when related to muscle mass. The finding of normal 3-MH excretion in myotonic dystrophy suggests that the muscle wasting in this disorder results from impaired anabolic processes rather than accelerated muscle destruction

  15. How Do People Cope with Muscular Dystrophy?

    Science.gov (United States)

    ... topic are answered in this section. How do people cope with muscular dystrophy (MD)? Although MD presents ... improve health and quality of life. Almost all people with any form of MD experience a worsening ...

  16. Muscle MRI and functional outcome measures in Becker muscular dystrophy.

    Science.gov (United States)

    Barp, Andrea; Bello, Luca; Caumo, Luca; Campadello, Paola; Semplicini, Claudio; Lazzarotto, Annalisa; Sorarù, Gianni; Calore, Chiara; Rampado, Alessandro; Motta, Raffaella; Stramare, Roberto; Pegoraro, Elena

    2017-11-22

    Becker muscular dystrophy (BMD) is a neuromuscular disorder allelic to Duchenne muscular dystrophy (DMD), caused by in-frame mutations in the dystrophin gene, and characterized by a clinical progression that is both milder and more heterogeneous than DMD. Muscle magnetic resonance imaging (MRI) has been proposed as biomarker of disease progression in dystrophinopathies. Correlation with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification. In this study, 51 molecularly confirmed BMD patients (aged 7-69 years) underwent muscle MRI and were evaluated with functional measures (NSAA and 6MWT) at the time of the MRI, and subsequently after one year. We confirmed a pattern of fatty substitution involving mainly the hip extensors and most thigh muscles. Severity of muscle fatty substitution was significantly correlated with specific DMD mutations: in particular, patients with an isolated deletion of exon 48, or deletions bordering exon 51, showed milder involvement. Fat infiltration scores correlated with baseline functional measures, and predicted changes after 1 year. We conclude that in BMD, skeletal muscle MRI not only strongly correlates with motor function, but also helps in predicting functional deterioration within a 12-month time frame.

  17. Posterior amorphous corneal dystrophy: case report

    OpenAIRE

    Oliveira, Lauro Augusto de [UNIFESP; Vieira, Luiz Antônio [UNIFESP; Freitas, Denise de [UNIFESP; Sousa, Luciene Barbosa de [UNIFESP

    2006-01-01

    O objetivo deste trabalho é alertar o oftalmologista da possibilidade de se deparar com casos raros de distrofias corneanas. Neste caso correlacionamos os achados clínicos da distrofia amorfa posterior com refração, topografia e biomicroscopia ultra-sônica.The purpose of this paper is to warn the ophthalmologist about the possibility of facing rare cases of corneal dystrophies. Clinical findings of a case of posterior amorphous dystrophy were correlated with refraction, topography, and ultras...

  18. Sleep disturbances in myotonic dystrophy type 2

    OpenAIRE

    Shepard, Paul; Lam, Erek M.; St. Louis, Erik K.; Dominik, Jacob

    2012-01-01

    Sleep disorders in myotonic dystrophy type 1 (DM1) are common and include sleep disordered breathing (SDB), hypersomnia, and fatigue. Little is known regarding the occurrence of sleep disturbance in myotonic dystrophy type 2 (DM2). We hypothesized that DM2 patients may frequently harbor sleep disorders. We reviewed medical records of all genetically confirmed cases of DM2 seen at our sleep center between 1997 and 2010 for demographic, laboratory, overnight oximetry, and polysomnography (PSG) ...

  19. Duchenne muscular dystrophy: the management of scoliosis

    Science.gov (United States)

    Gardner, Adrian C.; Roper, Helen P.; Chikermane, Ashish A.; Tatman, Andrew J.

    2016-01-01

    This study summaries the current management of scoliosis in patients with Duchenne Muscular Dystrophy. A literature review of Medline was performed and the collected articles critically appraised. This literature is discussed to give an overview of the current management of scoliosis within Duchenne Muscular Dystrophy. Importantly, improvements in respiratory care, the use of steroids and improving surgical techniques have allowed patients to maintain quality of life and improved life expectancy in this patient group. PMID:27757431

  20. Studying Dynamic Features in Myocardial Infarction Progression by Integrating miRNA-Transcription Factor Co-Regulatory Networks and Time-Series RNA Expression Data from Peripheral Blood Mononuclear Cells.

    Directory of Open Access Journals (Sweden)

    Hongbo Shi

    Full Text Available Myocardial infarction (MI is a serious heart disease and a leading cause of mortality and morbidity worldwide. Although some molecules (genes, miRNAs and transcription factors (TFs associated with MI have been studied in a specific pathological context, their dynamic characteristics in gene expressions, biological functions and regulatory interactions in MI progression have not been fully elucidated to date. In the current study, we analyzed time-series RNA expression data from peripheral blood mononuclear cells. We observed that significantly differentially expressed genes were sharply up- or down-regulated in the acute phase of MI, and then changed slowly until the chronic phase. Biological functions involved at each stage of MI were identified. Additionally, dynamic miRNA-TF co-regulatory networks were constructed based on the significantly differentially expressed genes and miRNA-TF co-regulatory motifs, and the dynamic interplay of miRNAs, TFs and target genes were investigated. Finally, a new panel of candidate diagnostic biomarkers (STAT3 and ICAM1 was identified to have discriminatory capability for patients with or without MI, especially the patients with or without recurrent events. The results of the present study not only shed new light on the understanding underlying regulatory mechanisms involved in MI progression, but also contribute to the discovery of true diagnostic biomarkers for MI.

  1. Cardiac involvement in patients with limb-girdle muscular dystrophy type 2 and Becker muscular dystrophy

    DEFF Research Database (Denmark)

    Sveen, Marie-Louise; Thune, Jens Jakob; Køber, Lars

    2008-01-01

    OBJECTIVE: To investigate the extent of cardiac involvement in patients with 1 of the 12 groups of recessively inherited limb-girdle muscular dystrophy type 2 (LGMD2A-L) and Becker muscular dystrophy (BMD). DESIGN: Prospective screening. SETTING: Neuromuscular Clinic and Department of Cardiology...

  2. Reliability of kinetic visual field testing in children with mutation-proven retinal dystrophies: Implications for therapeutic clinical trials.

    Science.gov (United States)

    Dedania, Vaidehi S; Liu, Jerry Y; Schlegel, Dana; Andrews, Chris A; Branham, Kari; Khan, Naheed W; Musch, David C; Heckenlively, John R; Jayasundera, K Thiran

    2018-01-01

    Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration. Retrospective review of children ≤ 17 years old with a mutation-proven retinal dystrophy. Objective clinical disease activity was assessed by a retinal degeneration specialist masked to GVF results. Digital quantification of GVF area was performed. Twenty-nine children (58 eyes), ages 5-16, were identified. GVF area increased with age despite progression in 20 children and clinical stability in nine children. Mean ± standard error increase in GVF area/year was 333 ± 130 mm 2 (I4e, p = 0.012), 720 ± 155 mm 2 (III4e, p children with mutation-proven retinal dystrophies, there is a significant increase in GVF area with age, particularly those children with retinal dystrophies can be an unreliable measure of response to treatment and on which to base appropriate counseling about visual impairment.

  3. Clinical Manifestations and Overall Management Strategies for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Tsuda, Takeshi

    2018-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that causes progressive weakness and wasting of skeletal muscular and myocardium in boys due to mutation of dystrophin. The structural integrity of each individual skeletal and cardiac myocyte is significantly compromised upon physical stress due to the absence of dystrophin. The progressive destruction of systemic musculature and myocardium causes affected patients to develop multiple organ disabilities, including loss of ambulation, physical immobility, neuromuscular scoliosis, joint contracture, restrictive lung disease, obstructive sleep apnea, and cardiomyopathy. There are some central nervous system-related medical problems, as dystrophin is also expressed in the neuronal tissues. Although principal management is to mainly delay the pathological process, an enhanced understanding of underlying pathological processes has significantly improved quality of life and longevity for DMD patients. Future research in novel molecular approach is warranted to answer unanswered questions.

  4. Genetics Home Reference: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions APECED Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Printable PDF Open All Close All ... view the expand/collapse boxes. Description Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy ( APECED ) is an inherited condition that ...

  5. Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.

    Science.gov (United States)

    Waddell, Leigh B; Lemckert, Frances A; Zheng, Xi F; Tran, Jenny; Evesson, Frances J; Hawkes, Joanne M; Lek, Angela; Street, Neil E; Lin, Peihui; Clarke, Nigel F; Landstrom, Andrew P; Ackerman, Michael J; Weisleder, Noah; Ma, Jianjie; North, Kathryn N; Cooper, Sandra T

    2011-04-01

    Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners of dysferlin are also implicated in membrane resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 accumulates at sites of membrane damage, and MG53-knockout mice display a progressive muscular dystrophy. This study explored the expression and localization of MG53 in human skeletal muscle, how membrane repair proteins are modulated in various forms of muscular dystrophy, and whether MG53 is a primary cause of human muscle disease. Mitsugumin 53 showed variable sarcolemmal and/or cytoplasmic immunolabeling in control human muscle and elevated levels in dystrophic patients. No pathogenic MG53 mutations were identified in 50 muscular dystrophy patients, suggesting that MG53 is unlikely to be a common cause of muscular dystrophy in Australia. Western blot analysis confirmed upregulation of MG53, as well as of dysferlin, annexin A1, and caveolin-3 to different degrees, in different muscular dystrophies. Importantly, MG53, annexin A1, and dysferlin localize to the t-tubule network and show enriched labeling at longitudinal tubules of the t-system in overstretch. Our results suggest that longitudinal tubules of the t-system may represent sites of physiological membrane damage targeted by this membrane repair complex.

  6. ROLE OF METABOLIC THERAPY IN TREATMENT OF MYOCARDIUM DYSTROPHY IN CHILDREN

    Directory of Open Access Journals (Sweden)

    A.L. Frolenko

    2010-01-01

    Full Text Available The objective of present research was studying of influence of co-enzyme Q10 (Kudesan on cardiovascular system in children with myocardial dystrophy (MCD. Patients were divided on two comparable groups (n = 20 and n = 28 according to clinical symptoms of MCD, changes on electrocardiogram (ECG and results of echocardiography. Patients received non-drug means (massage, physical training in treatment regimen, psycho- and reflexotherapy and vasoactive, nootropic and sedative medications; patients from 2nd group were additionally treated with co-enzyme Q10 during 4 weeks. It was shown that inclusion of co-enzyme Q10 in complex treatment of MCD resulted in beneficial effect on self-feeling of child, favored to disappearance of repolarization disorders on ECG and increase of ejectional fraction. Thus, using of co-enzyme Q10 in complex treatment of children with MCD is reasonable. Key words: children, myocardial dystrophy, co-enzyme Q10, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(5:18-23

  7. Measurement of the Functional Status of Patients with Different Types of Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Yi-Jing Lue

    2009-06-01

    Full Text Available Muscular dystrophy (MD comprises a group of diseases characterized by progressive muscle weakness that induces functional deterioration. Clinical management requires the use of a well-designed scale to measure patients' functional status. This study aimed to investigate the quality of the functional scales used to assess patients with different types of MD. The Brooke scale and the Vignos scale were used to grade arm and leg function, respectively. The Barthel Index was used to evaluate the function of daily living activity. We performed tests to assess the acceptability of these scales. The characteristics of the different types of MD are discussed. This was a multicenter study and included patients diagnosed with Duchenne muscular dystrophy (DMD (classified as severely progressive MD, Becker muscular dystrophy (BMD, limb girdle muscular dystrophy (LGMD and facioscapulohumeral muscular dystrophy (FSHD. BMD, LGMD, and FSHD were classified as slowly progressive MD. The results demonstrated that the Brooke scale was acceptable for grading arm function in DMD, but was unable to discriminate between differing levels of severity in slowly progressive MD. The floor effect was large for all types of slowly progressive MD (range, 20.0–61.9, and was especially high for BMD. The floor effect was also large for BMD (23.8% and FSHD (50.0% using the Vignos scale. Grades 6–8 of the Vignos scale were inapplicable because they included items involving the use of long leg braces for walking or standing, and some patients did not use long leg braces. In the Barthel Index, a ceiling effect was prominent for slowly progressive MD (58.9%, while a floor effect existed for DMD (17.9%. Among the slowly progressive MDs, FSHD patients had the best level of functioning; they had better leg function and their daily living activities were less affected than patients with other forms of slowly progressive MD. The results of this study demonstrate the acceptability of the

  8. Respiratory muscle decline in Duchenne muscular dystrophy.

    Science.gov (United States)

    Khirani, Sonia; Ramirez, Adriana; Aubertin, Guillaume; Boulé, Michèle; Chemouny, Chrystelle; Forin, Véronique; Fauroux, Brigitte

    2014-05-01

    Duchenne muscular dystrophy (DMD) causes progressive respiratory muscle weakness. The aim of the study was to analyze the trend of a large number of respiratory parameters to gain further information on the course of the disease. Retrospective study. 48 boys with DMD, age range between 6 and 19 year old, who were followed in our multidisciplinary neuromuscular clinic between 2001 and 2011. Lung function, blood gases, respiratory mechanics, and muscle strength were measured during routine follow-up over a 10-year period. Only data from patients with at least two measurements were retained. The data of 28 patients were considered for analysis. Four parameters showed an important decline with age. Gastric pressure during cough (Pgas cough) was below normal in all patients with a mean decline of 5.7 ± 3.8 cmH2 O/year. Sniff nasal inspiratory pressure (SNIP) tended to increase first followed by a rapid decline (mean decrease 4.8 ± 4.9 cmH2 O; 5.2 ± 4.4% predicted/year). Absolute forced vital capacity (FVC) values peaked around the age of 13-14 years and remained mainly over 1 L but predicted values showed a mean 4.1 ± 4.4% decline/year. Diaphragmatic tension-time index (TTdi) increased above normal values after the age of 14 years with a mean increase of 0.04 ± 0.04 point/year. This study confirms the previous findings that FVC and SNIP are among the most important parameters to monitor the evolution of DMD. Expiratory muscle strength, assessed by Pgas cough, and the endurance index, TTdi, which are reported for the first time in a large cohort, appeared to be informative too, even though measured through an invasive method. © 2013 Wiley Periodicals, Inc.

  9. Myocardial perfusion in silent myocardial ischemia

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi; Murano, Kenichi; Usami, Masahisa

    1989-01-01

    To investigate myocardial perfusion in silent myocardial ischemia, we performed exercise stress myocardial tomography with thallium-201 (Tl) in 85 patients with coronary artery disease (CAD). Exercise stress myocardial tomography was obtained both immediately after exercise and three hours later. Patients were classified into two groups according to the presence (Symptomatic Group, n=36) or absence (Silent Group, n=49) of chest pain during exercise stress. Clinical features (age, gender and history of myocardial infarction) and arteriographically determined severity of CAD were the same in both groups. The extent of myocardial ischemia (% Ischemia) estimated by exercise stress myocardial tomography was the same in each group (30±10 % in Silent Group, 28±12 % in Symptomatic Group, NS). The severity of exercise-induced myocardial ischemia was expressed as a minimal value of myocardial Tl washout rate (minimal WOR) of each patient. Although exercise heart rate was identical in both groups, minimal WOR in Silent Group was significantly higher than that of Symptomatic Group (4±10% vs -16±14%, p<0.001). The study in patients who exhibited both silent and symptomatic ischemia showed the same results. These findings suggest that the severity of ischemia is a fundamental factor in determining the presence or absence of pain during exercise induced ischemia. (author)

  10. Radioimmunoassay for human myoglobin: methods and results in patients with skeletal muscle or myocardial disorders

    International Nuclear Information System (INIS)

    Miyoshi, K.; Saito, S.; Kawai, H.; Kondo, A.; Iwasa, M.; Hayashi, T.; Yagita, M.

    1978-01-01

    A sensitive and specific radioimmunoassay has been developed for the measurement of serum Mb. Immunization of rabbit with human Mb yielded anti-Mb antibody which was purified by affinity chromatography. Human hemoglobin, CK, and the component of serum per se did not appear to cross-react with the antibody. Mb was radiolabeled by the chloramine T method. The radioimmunoassay method could detect as little as 0.3 ng of Mb and was not affected by hemolysis. Information is also given on precision, recovery, and specimen preservation. Mb levels could be detected in all of 120 normal adults, and the values ranged between 1 and 28 ng/ml (mean, 13.1 +- 6.1). No sex difference was observed. Levels were markedly elevated in all the patients with progressive muscular dystrophy, especially in the Duchenne type at the level of 40 to 1700 ng/ml. It was also noticed that about 70% of female gene carriers of Duchenne type had a slightly increased Mb level. An elevated serum Mb was also noted in polymyositis. In every case of acute myocardial infarction, serum Mb levels were increased, peak values ranging from 175 to 4400 ng/ml and averaging 1162 +- 287.9 Mb levels were elevated faster and peaked earlier (within 6 to 12 hr after the attack) than serum CK activity and returned to nearly normal range within 3 to 4 days. The increase in serum Mb was also noticed in shock and surgery. These data indicate that radioimmunoassay of Mb is a useful test for judging the myolytic state of myogenic myopathies and for early detection of myocardial infarction

  11. Duchenne and Becker muscular dystrophy in adolescents: current perspectives.

    Science.gov (United States)

    Andrews, Jennifer G; Wahl, Richard A

    2018-01-01

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are life-limiting and progressive neuromuscular conditions with significant comorbidities, many of which manifest during adolescence. BMD is a milder presentation of the condition and much less prevalent than DMD, making it less represented in the literature, or more severely affected individuals with BMD may be subsumed into the DMD population using clinical cutoffs. Numerous consensus documents have been published on the clinical management of DMD, the most recent of which was released in 2010. The advent of these clinical management consensus papers, particularly respiratory care, has significantly increased the life span for these individuals, and the adolescent years are now a point of transition into adult lives, rather than a period of end of life. This review outlines the literature on DMD and BMD during adolescence, focusing on clinical presentation during adolescence, impact of living with a chronic illness on adolescents, and the effect that adolescents have on their chronic illness. In addition, we describe the role that palliative-care specialists could have in improving outcomes for these individuals. The increasing proportion of individuals with DMD and BMD living into adulthood underscores the need for more research into interventions and intracacies of adolescence that can improve the social aspects of their lives.

  12. Meretoja’s Syndrome: Lattice Corneal Dystrophy, Gelsolin Type

    Directory of Open Access Journals (Sweden)

    I. Casal

    2017-01-01

    Full Text Available Lattice corneal dystrophy gelsolin type was first described in 1969 by Jouko Meretoja, a Finnish ophthalmologist. It is caused by an autosomal dominant mutation in gelsolin gene resulting in unstable protein fragments and amyloid deposition in various organs. The age of onset is usually after the third decade of life and typical diagnostic triad includes progressive bilateral facial paralysis, loose skin, and lattice corneal dystrophy. We report a case of a 53-year-old female patient referred to our Department of Ophthalmology by severe dry eye and incomplete eyelid closure. She had severe bilateral facial paresis, significant orbicularis, and perioral sagging as well as hypoesthesia of extremities and was diagnosed with Meretoja’s syndrome at the age of 50, confirmed by the presence of gelsolin mutation. At our observation she had bilateral diminished tear film break-up time and Schirmer test, diffuse keratitis, corneal opacification, and neovascularization in the left eye. She was treated with preservative-free lubricants and topical cyclosporine, associated with nocturnal complete occlusion of both eyes, and underwent placement of lacrimal punctal plugs. Ocular symptoms are the first to appear and our role as ophthalmologists is essential for the diagnosis, treatment, and monitoring of ocular alterations in these patients.

  13. Clinical-Diagnostic Features of Duchenne Muscular Dystrophy in Children

    Directory of Open Access Journals (Sweden)

    Umida T. Omonova

    2013-12-01

    Full Text Available Duchenne Muscular Dystrophy (DMD is a severe, progressive disease that affects about 1 out of every 5,000 male infants; this is the most destructive of all muscular dystrophies, which worsens rapidly. In this study, we performed a clinical analysis of 37 children with DMD. They ranged in age from 3 to 15 years, mean age being 7.8±0.48 years. The mean age at onset was 4.3±0.36 years and ranged from birth to 8 years. The biochemical examination included the determination of the serum levels of the following enzymes, AST, ALT, CPK-MM, and LDH. A genealogical analysis was conducted among 240 first-degree relatives of children with DMD. Electroneuromyography examination included registration of the biopotentials of the hand and foot muscles, measurement of the muscle response (M-wave and the late-evoked responses. The clinical-diagnostic features of DMD in children were characterized.

  14. Duchenne and Becker muscular dystrophy in adolescents: current perspectives

    Science.gov (United States)

    Andrews, Jennifer G; Wahl, Richard A

    2018-01-01

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are life-limiting and progressive neuromuscular conditions with significant comorbidities, many of which manifest during adolescence. BMD is a milder presentation of the condition and much less prevalent than DMD, making it less represented in the literature, or more severely affected individuals with BMD may be subsumed into the DMD population using clinical cutoffs. Numerous consensus documents have been published on the clinical management of DMD, the most recent of which was released in 2010. The advent of these clinical management consensus papers, particularly respiratory care, has significantly increased the life span for these individuals, and the adolescent years are now a point of transition into adult lives, rather than a period of end of life. This review outlines the literature on DMD and BMD during adolescence, focusing on clinical presentation during adolescence, impact of living with a chronic illness on adolescents, and the effect that adolescents have on their chronic illness. In addition, we describe the role that palliative-care specialists could have in improving outcomes for these individuals. The increasing proportion of individuals with DMD and BMD living into adulthood underscores the need for more research into interventions and intracacies of adolescence that can improve the social aspects of their lives. PMID:29588625

  15. Molecular and phenotypic analysis of a family with autosomal recessive cone-rod dystrophy and Stargardt disease.

    NARCIS (Netherlands)

    Ijzer, Suzanne; Born, L.I. van den; Zonneveld, M.N.; Lopez, I.; Ayyagari, R.; Teye-Botchway, L.; Mota-Vieira, L.; Cremers, F.P.M.; Koenekoop, R.K.

    2007-01-01

    PURPOSE: To identify the causative gene mutations in three siblings with severe progressive autosomal recessive cone-rod dystrophy (arCRD) and their fifth paternal cousin with Stargardt disease (STGD1) and to specify the phenotypes. METHODS: We evaluated eight sibs of one family, three family

  16. Radiographic and ultrasonographic features of hypertrophic feline muscular dystrophy in two cats

    International Nuclear Information System (INIS)

    Berry, C.R.; Gaschen, F.P.; Ackerman, N.

    1992-01-01

    Hypertrophic fellne musculer dystrophy has been reported as an X-linked inherited deficiency of a cytoskeletal myofiber protein called dystrophin. This report deserlbes the radiographic and ultrasonographic abnormalities of two male littermate domestic short-hair cats and reviews the previous reported findings assoclated with hypertrophic feline muscular dystrophy. The thoracic radiographic abnormalities included: progressive cardiomegaly, large convex, scalloped irregularities associated with the vetral aspect of the diaphragm, and variable degrees of esophageal dilation (megaesophagus) with associated cranioventral aspiration pneumonia. Echocardiographic features included: concentric left vetricular wall thickening, increased left ventricular and diastolic and systolic dimensions, and an increase in endocardial echogenicity. Abdominal radiographic abnormalities included: hepatosplenomegaly, peritoneal effusion, renomegaly, adrenal gland mineralization, and paralumbar and diaphragmatic musculature enlargement. Abdomlnal ultrasonographic abnormalities included: irregularly thickened muscular portion of the diaphragm; hypoechogenicity of the liver; peritoneal effusion; hepatosplenomegaly; renomegaly with hyperechoic cortex and medulla; and adrenal gland mineralization. The irregular scalloped appearance of the diaphragm (particularly along the ventral/sternal margin) was a consistenl radiographic abnormlity in the two cats with hypertrophic feline muscular dystrophy after the age of 7 months. This finding was confirmed by ultrasound as a thickened irregular, hyperechoic diaphragm. A diagnosis of hypertrophic feline muscular dystrophy should be strongly suspected if this abnormality is identified

  17. Zebrafish models flex their muscles to shed light on muscular dystrophies.

    Science.gov (United States)

    Berger, Joachim; Currie, Peter D

    2012-11-01

    Muscular dystrophies are a group of genetic disorders that specifically affect skeletal muscle and are characterized by progressive muscle degeneration and weakening. To develop therapies and treatments for these diseases, a better understanding of the molecular basis of muscular dystrophies is required. Thus, identification of causative genes mutated in specific disorders and the study of relevant animal models are imperative. Zebrafish genetic models of human muscle disorders often closely resemble disease pathogenesis, and the optical clarity of zebrafish embryos and larvae enables visualization of dynamic molecular processes in vivo. As an adjunct tool, morpholino studies provide insight into the molecular function of genes and allow rapid assessment of candidate genes for human muscular dystrophies. This unique set of attributes makes the zebrafish model system particularly valuable for the study of muscle diseases. This review discusses how recent research using zebrafish has shed light on the pathological basis of muscular dystrophies, with particular focus on the muscle cell membrane and the linkage between the myofibre cytoskeleton and the extracellular matrix.

  18. SIRT1: A Novel Target for the Treatment of Muscular Dystrophies

    Directory of Open Access Journals (Sweden)

    Atsushi Kuno

    2016-01-01

    Full Text Available Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. Duchenne muscular dystrophy (DMD is the most common and severe form of muscular dystrophy and is caused by mutations in the gene that encodes the cytoskeletal protein dystrophin. The treatment for DMD is limited to glucocorticoids, which are associated with multiple side effects. Thus, the identification of novel therapeutic targets is urgently needed. SIRT1 is an NAD+-dependent histone/protein deacetylase that plays roles in diverse cellular processes, including stress resistance and cell survival. Studies have shown that SIRT1 activation provides beneficial effects in the dystrophin-deficient mdx mouse, a model of DMD. SIRT1 activation leads to the attenuation of oxidative stress and inflammation, a shift from the fast to slow myofiber phenotype, and the suppression of tissue fibrosis. Although further research is needed to clarify the molecular mechanisms underlying the protective role of SIRT1 in mdx mice, we propose SIRT1 as a novel therapeutic target for patients with muscular dystrophies.

  19. The experiences of patients with Duchenne muscular dystrophy in facing and learning about their clinical conditions.

    Science.gov (United States)

    Fujino, Haruo; Iwata, Yuko; Saito, Toshio; Matsumura, Tsuyoshi; Fujimura, Harutoshi; Imura, Osamu

    2016-01-01

    Patients experience extreme difficulty when facing an intractable genetic disease. Herein, we examine the experiences of patients with Duchenne muscular dystrophy in facing and learning about their disease. A total of seven patients with Duchenne muscular dystrophy (age range: 20-48) participated. We conducted in-depth interviews with them about how they learned of their disease and how their feelings regarding the disease changed over time. Transcribed data were analysed using thematic analysis. The following themes emerged from this analysis: "experiences before receiving the diagnosis," "experiences when they learned of their condition and progression of the disease," "supports," and "desired explanations." Anxiety and worry were most pronounced when they had to transition to using wheelchairs or respirators due to disease progression; indeed, such transitions affect the patients psychological adjustment. In such times, support from significant others in their lives helped patients adjust.

  20. Current and emerging treatment strategies for Duchenne muscular dystrophy

    Science.gov (United States)

    Mah, Jean K

    2016-01-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying

  1. Orthodontic treatment in a patient with unilateral open-bite and Becker muscular dystrophy. A 5-year follow-up

    Directory of Open Access Journals (Sweden)

    Juan Fernando Aristizabal

    2014-12-01

    Full Text Available INTRODUCTION: Becker muscular dystrophy is an X-chromosomal linked anomaly characterized by progressive muscle wear and weakness. This case report shows the orthodontic treatment of a Becker muscular dystrophy patient with unilateral open bite.METHODS: To correct patient's malocclusion, general anesthesia and orthognathic surgery were not considered as an option. Conventional orthodontic treatment with intermaxillary elastics and muscular functional therapy were employed instead.RESULTS: After 36 months, open bite was corrected. The case remains stable after a 5-year post-treatment retention period.

  2. Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy.

    Science.gov (United States)

    Galindo, Cristi L; Soslow, Jonathan H; Brinkmeyer-Langford, Candice L; Gupte, Manisha; Smith, Holly M; Sengsayadeth, Seng; Sawyer, Douglas B; Benson, D Woodrow; Kornegay, Joe N; Markham, Larry W

    2016-04-01

    In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.

  3. Evaluation of Disturbance in Gait and standing balance of patients with Duchenne musclar dystrophy

    OpenAIRE

    林, 良一; 桑原, 英明

    1992-01-01

    Abilities of standing and gait decreased progressively, with decrease of the activity of daily living (ADL), from early school ages in patients with Duchenne muscular dystrophy. In this paper, serial measurements of abilities in patient's gait and standing were studied to assess the clinico-pathophysiological aspects of this disease. Changes in a decrease of contact area of foot to a floor paralleled to the degree of forward shift of body center of gravity during standing. Foot-prints during ...

  4. Median nail dystrophy involving the thumb nail

    Directory of Open Access Journals (Sweden)

    Rahulkrishna Kota

    2016-01-01

    Full Text Available Median canaliform dystrophy of Heller is a rare entity characterized by a midline or a paramedian ridge or split and canal formation in nail plate of one or both the thumb nails. It is an acquired condition resulting from a temporary defect in the matrix that interferes with nail formation. Habitual picking of the nail base may be responsible for some cases. Histopathology classically shows parakeratosis, accumulation of melanin within and between the nail bed keratinocytes. Treatment of median nail dystrophy includes injectable triamcinalone acetonide, topical 0.1% tacrolimus, and tazarotene 0.05%, which is many a times challenging for a dermatologist. Psychiatric opinion should be taken when associated with the depressive, obsessive-compulsive, or impulse-control disorder. We report a case of 19-year-old male diagnosed as median nail dystrophy.

  5. Classification of myocardial infarction

    DEFF Research Database (Denmark)

    Saaby, Lotte; Poulsen, Tina Svenstrup; Hosbond, Susanne Elisabeth

    2013-01-01

    The classification of myocardial infarction into 5 types was introduced in 2007 as an important component of the universal definition. In contrast to the plaque rupture-related type 1 myocardial infarction, type 2 myocardial infarction is considered to be caused by an imbalance between demand...

  6. RNA interference gene therapy in dominant retinitis pigmentosa and cone-rod dystrophy mouse models caused by GCAP1 mutations

    Directory of Open Access Journals (Sweden)

    Li eJiang

    2014-04-01

    Full Text Available RNA interference (RNAi knockdown is an efficacious therapeutic strategy for silencing genes causative for dominant retinal dystrophies. To test this, we used self-complementary (sc AAV2/8 vector to develop an RNAi-based therapy in two dominant retinal degeneration mouse models. The allele-specific model expresses transgenic bovine GCAP1(Y99C establishing a rapid RP-like phenotype, whereas the nonallele-specific model expresses mouse GCAP1(L151F producing a slowly progressing cone/rod dystrophy (CORD. The late onset GCAP1(L151F-CORD mimics the dystrophy observed in human GCAP1-CORD patients. Subretinal injection of scAAV2/8 carrying shRNA expression cassettes specific for bovine or mouse GCAP1 showed strong expression at one week post-injection. In both allele-specific (GCAP1(Y99C-RP and nonallele-specific (GCAP1(L151F-CORD models of dominant retinal dystrophy, RNAi-mediated gene silencing enhanced photoreceptor survival, delayed onset of degeneration and improved visual function. Such results provide a proof of concept toward effective RNAi-based gene therapy mediated by scAAV2/8 for dominant retinal disease based on GCAP1 mutation. Further, nonallele-specific RNAi knockdown of GCAP1 may prove generally applicable toward the rescue of any human GCAP1-based dominant cone-rod dystrophy.

  7. A Human Pluripotent Stem Cell Model of Facioscapulohumeral Muscular Dystrophy-Affected Skeletal Muscles.

    Science.gov (United States)

    Caron, Leslie; Kher, Devaki; Lee, Kian Leong; McKernan, Robert; Dumevska, Biljana; Hidalgo, Alejandro; Li, Jia; Yang, Henry; Main, Heather; Ferri, Giulia; Petek, Lisa M; Poellinger, Lorenz; Miller, Daniel G; Gabellini, Davide; Schmidt, Uli

    2016-09-01

    : Facioscapulohumeral muscular dystrophy (FSHD) represents a major unmet clinical need arising from the progressive weakness and atrophy of skeletal muscles. The dearth of adequate experimental models has severely hampered our understanding of the disease. To date, no treatment is available for FSHD. Human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies. We developed a scalable monolayer system to differentiate hESCs into mature SkMCs within 26 days, without cell sorting or genetic manipulation. Here we show that SkMCs derived from FSHD1-affected hESC lines exclusively express the FSHD pathogenic marker double homeobox 4 and exhibit some of the defects reported in FSHD. FSHD1 myotubes are thinner when compared with unaffected and Becker muscular dystrophy myotubes, and differentially regulate genes involved in cell cycle control, oxidative stress response, and cell adhesion. This cellular model will be a powerful tool for studying FSHD and will ultimately assist in the development of effective treatments for muscular dystrophies. This work describes an efficient and highly scalable monolayer system to differentiate human pluripotent stem cells (hPSCs) into skeletal muscle cells (SkMCs) and demonstrates disease-specific phenotypes in SkMCs derived from both embryonic and induced hPSCs affected with facioscapulohumeral muscular dystrophy. This study represents the first human stem cell-based cellular model for a muscular dystrophy that is suitable for high-throughput screening and drug development. ©AlphaMed Press.

  8. Myocardial imaging. Coxsackie myocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  9. Myocardial imaging. Coxsackie myocarditis

    International Nuclear Information System (INIS)

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-01-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1

  10. MRI as outcome measure in facioscapulohumeral muscular dystrophy

    DEFF Research Database (Denmark)

    Andersen, Grete; Dahlqvist, Julia R; Vissing, Christoffer R

    2017-01-01

    There is no effective treatment available for facioscapulohumeral muscular dystrophy type 1 (FSHD1), but emerging therapies are under way that call for a better understanding of natural history in this condition. In this prospective, longitudinal study, we used quantitative MRI to assess yearly...... disease progression in patients with FSHD1. Ambulatory patients with confirmed diagnosis of FSHD1 (25/20 men/women, age 20-75 years, FSHD score: 0-12) were tested with 359-560-day interval between tests. Using the MRI Dixon technique, muscle fat replacement was evaluated in paraspinal, thigh, and calf...... muscles. Changes were compared with those in FSHD score, muscle strength (hand-held dynamometry), 6-minute-walk-distance, 14-step-stair-test, and 5-time-sit-to-stand-test. Composite absolute fat fraction of all assessed muscles increased by 0.036 (CI 0.026-0.046, P

  11. Understanding the Process of Fibrosis in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Yacine Kharraz

    2014-01-01

    Full Text Available Fibrosis is the aberrant deposition of extracellular matrix (ECM components during tissue healing leading to loss of its architecture and function. Fibrotic diseases are often associated with chronic pathologies and occur in a large variety of vital organs and tissues, including skeletal muscle. In human muscle, fibrosis is most readily associated with the severe muscle wasting disorder Duchenne muscular dystrophy (DMD, caused by loss of dystrophin gene function. In DMD, skeletal muscle degenerates and is infiltrated by inflammatory cells and the functions of the muscle stem cells (satellite cells become impeded and fibrogenic cells hyperproliferate and are overactivated, leading to the substitution of skeletal muscle with nonfunctional fibrotic tissue. Here, we review new developments in our understanding of the mechanisms leading to fibrosis in DMD and several recent advances towards reverting it, as potential treatments to attenuate disease progression.

  12. The role and clinical value of thallium-201 myocardial scintigraphy in ischemic heart disease

    International Nuclear Information System (INIS)

    Shimada, Tomoyoshi; Nakamori, Hisato; Kurimoto, Toru; Karakawa, Masahiro; Matsuura, Takashi; Iwasaka, Toshiji; Inada, Mitsuo; Nishiyama, Yutaka

    1990-01-01

    To define the role and clinical value of thallium-201 myocardial scintigraphy in ischemic heart disease, 967 consecutive patients refered to our laboratory since 1985 were studied. The purpose of scintigraphy have changed from diagnosing of myocardial ischemia to assessing myocardial viability with the progress of coronary angioplasty. At present, thallium-201 myocardial scintigraphy have become indispensable noninvasive method for the management of patients with ischemic heart disease. (author)

  13. Cardiomyopathy in becker muscular dystrophy: Overview.

    Science.gov (United States)

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-06-26

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed.

  14. Respiratory muscle training in Duchenne muscular dystrophy.

    OpenAIRE

    Rodillo, E; Noble-Jamieson, C M; Aber, V; Heckmatt, J Z; Muntoni, F; Dubowitz, V

    1989-01-01

    Twenty two boys with Duchenne muscular dystrophy were entered into a randomised double blind crossover trial to compare respiratory muscle training with a Triflow II inspirometer and 'placebo' training with a mini peak flow meter. Supine posture was associated with significantly impaired lung function, but respiratory muscle training showed no benefit.

  15. What Are the Treatments for Muscular Dystrophy?

    Science.gov (United States)

    ... Child Neurology Society. (2005). Practice parameter: Corticosteroid treatment of Duchenne dystrophy. Neurology, 64 , 13-20. Retrieved June 22, 2012, ... Statement. (2004). Respiratory care of the patient with Duchenne muscular ... American Journal of Respiratory and Critical Care Medicine, 170, 456-465. ...

  16. Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy

    Science.gov (United States)

    De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

    2010-01-01

    Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

  17. Brain Function in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2002-02-01

    Full Text Available The role of dystrophin disorders in the CNS function of boys with Duchenne muscular dystrophy (DMD and the dystrophin-deficient mdx mouse, an animal model of DMD, is reviewed at the University of New South Wales, University of Sydney, Australia.

  18. Duchenne muscular dystrophy - a molecular service

    African Journals Online (AJOL)

    In 1987 a carrier detection and prenatal diagnostic service for. Duchenne muscular dystrophy using molecular technology was instituted at the Department of Human Genetics, Uni- versity of Cape Town, to serve affe.cted families in southern. Africa. DNA samples from 100 affected male subjects and. 350 of their relatives ...

  19. Aberrant Myokine Signaling in Congenital Myotonic Dystrophy

    Directory of Open Access Journals (Sweden)

    Masayuki Nakamori

    2017-10-01

    Full Text Available Summary: Myotonic dystrophy types 1 (DM1 and 2 (DM2 are dominantly inherited neuromuscular disorders caused by a toxic gain of function of expanded CUG and CCUG repeats, respectively. Although both disorders are clinically similar, congenital myotonic dystrophy (CDM, a severe DM form, is found only in DM1. CDM is also characterized by muscle fiber immaturity not observed in adult DM, suggesting specific pathological mechanisms. Here, we revealed upregulation of the interleukin-6 (IL-6 myokine signaling pathway in CDM muscles. We also found a correlation between muscle immaturity and not only IL-6 expression but also expanded CTG repeat length and CpG methylation status upstream of the repeats. Aberrant CpG methylation was associated with transcriptional dysregulation at the repeat locus, increasing the toxic RNA burden that upregulates IL-6. Because the IL-6 pathway is involved in myocyte maturation and muscle atrophy, our results indicate that enhanced RNA toxicity contributes to severe CDM phenotypes through aberrant IL-6 signaling. : Congenital myotonic dystrophy (CDM manifests characteristic genetic (very large CTG repeat expansions, epigenetic (CpG hypermethylation upstream of the repeat, and phenotypic (muscle immaturity features not seen in adult DM. Nakamori et al. find phenotype-genotype and epigenotype correlation in CDM muscle and reveal involvement of the IL-6 myokine signaling pathway in the disease process. Keywords: CTCF, ER stress, IL-6, muscular dystrophy, NF-κB, trinucleotide, cytokine, splicing

  20. Emerging strategies for cell and gene therapy of the muscular dystrophies

    OpenAIRE

    Muir, Lindsey A.; Chamberlain, Jeffrey S.

    2009-01-01

    The muscular dystrophies are a heterogeneous group of over 40 disorders that are characterised by muscle weakness and wasting. The most common are Duchenne muscular dystrophy and Becker muscular dystrophy, which result from mutations within the gene encoding dystrophin; myotonic dystrophy type 1, which results from an expanded trinucleotide repeat in the myotonic dystrophy protein kinase gene; and facioscapulohumeral dystrophy, which is associated with contractions in the subtelomeric region ...

  1. Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2.

    Science.gov (United States)

    Witting, N; Duno, M; Vissing, J

    2013-01-01

    Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest that this unusual phenotype is caused by translation re-initiation downstream from the mutation site. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. [Two cases of Duchenne muscular dystrophy over 40 years after onset].

    Science.gov (United States)

    Ishizaki, Masatoshi; Ueyama, Hidetsugu; Masuda, Teruaki; Nishida, Yasuto; Imamura, Shigehiro; Ando, Yukio

    2013-01-01

    We report two 45 year old men with Duchenne muscular dystrophy. Case 1 showed a deleted exon 50 of the dystrophin gene by MLPA analysis, and Case 2 showed deleted exons 46-52. Both patients presented with severe weakness of the skeletal muscles and respiratory dysfunction, while cardiac involvement was mild and cognitive function was almost normal. The patients are able to shop at a mall, participate in activities, and attend hobbies, although they are bedridden with artificial respiration through tracheotomy. With the progress of the respiratory care and cardiac protective therapy, the prognosis of Duchenne muscular dystrophy has improved remarkably. At present, it is possible to survive over 40 years with maintenance of quality of life, if cardiac damage is not severe.

  3. A splice site mutation in laminin-α2 results in a severe muscular dystrophy and growth abnormalities in zebrafish.

    Directory of Open Access Journals (Sweden)

    Vandana A Gupta

    Full Text Available Congenital muscular dystrophy (CMD is a clinically and genetically heterogeneous group of inherited muscle disorders. In patients, muscle weakness is usually present at or shortly after birth and is progressive in nature. Merosin deficient congenital muscular dystrophy (MDC1A is a form of CMD caused by a defect in the laminin-α2 gene (LAMA2. Laminin-α2 is an extracellular matrix protein that interacts with the dystrophin-dystroglycan (DGC complex in membranes providing stability to muscle fibers. In an N-ethyl-N-nitrosourea mutagenesis screen to develop zebrafish models of neuromuscular diseases, we identified a mutant fish that exhibits severe muscular dystrophy early in development. Genetic mapping identified a splice site mutation in the lama2 gene. This splice site is highly conserved in humans and this mutation results in mis-splicing of RNA and a loss of protein function. Homozygous lama2 mutant zebrafish, designated lama2(cl501/cl501, exhibited reduced motor function and progressive degeneration of skeletal muscles and died at 8-15 days post fertilization. The skeletal muscles exhibited damaged myosepta and detachment of myofibers in the affected fish. Laminin-α2 deficiency also resulted in growth defects in the brain and eye of the mutant fish. This laminin-α2 deficient mutant fish represents a novel disease model to develop therapies for modulating splicing defects in congenital muscular dystrophies and to restore the muscle function in human patients with CMD.

  4. A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy

    Science.gov (United States)

    2018-04-17

    Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

  5. CINRG: Infrastructure for Clinical Trials in Duchenne Dystrophy

    Science.gov (United States)

    2013-09-01

    monitoring visit to monitor this study, the PITT0908 clinical trial, a study on facioscapulohumeral muscular dystrophy (FSHD), and PITT0112 Becker natural...height findings manuscript are currently in working stage and circulating among co-authors for editing. 2.3.6 Becker Muscular Dystrophy – A Natural...participants with Becker muscular dystrophy . The study period is 36 months per patient. This project is primarily funded by the National Institutes of

  6. Molecular mechanisms of muscle atrophy in myotonic dystrophies

    OpenAIRE

    Timchenko, Lubov

    2013-01-01

    Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are multisystemic diseases that primarily affect skeletal muscle, causing myotonia, muscle atrophy, and muscle weakness. DM1 and DM2 pathologies are caused by expansion of CTG and CCTG repeats in non-coding regions of the genes encoding myotonic dystrophy protein kinase (DMPK) and Zinc finger protein 9 (ZNF9) respectively. These expansions cause DM pathologies through accumulation of mutant RNAs that alter RNA metabolism in p...

  7. Functioning and disability in adults with myotonic dystrophy type 1.

    Science.gov (United States)

    Kierkegaard, Marie; Harms-Ringdahl, Karin; Holmqvist, Lotta Widén; Tollbäck, Anna

    2011-01-01

     To provide a comprehensive description of functioning and disability with regard to stages of disease progression in adults with myotonic dystrophy type 1 (DM1). Further to explore associations of measures of manual dexterity and of walking capacity with measures of activities of daily living (ADL) and participation in social and lifestyle activities. Seventy persons with DM1 underwent examinations, tests and answered questionnaires. Stages of disease progression were based on the muscular impairment rating scale.  Overweight, cardiac dysfunctions, respiratory restrictions, fatigue and/or low physical activity levels were found in approximately 40% of those with DM1. Over 75% had muscle impairments, and activity limitations in manual dexterity and walking. Dependence in personal and instrumental ADL was found in 16% and 39%, respectively, and participation restrictions in social and lifestyle activities in 52%. The presence of concurrent body-function impairments, activity limitations and participation restrictions was high. Significant differences were found in muscle impairment, manual dexterity, mobility, ADL and social and lifestyle activities with regard to disease progression. Cut-off values in measures of manual dexterity and walking capacity associated to functioning are proposed.  This information can be used for developing clinical practise and for health promotion for persons with DM1.

  8. CT finding and cerebrospinal fluid proteins in muscular dystrophy patients

    International Nuclear Information System (INIS)

    Hirase, Tsutomu; Ide, Masami; Araki, Shukuro; Okamoto, Hiroshi; Kawasaki, Shoichiro; Imamura, Shigehiro.

    1983-01-01

    We analyzed the microcomponents of protein fractions in the cerebrospinal fluid of patients with various types of muscular dystrophy. The degenerative pattern is characterized by an increase in the prealbumin and a decrease in the γ-globulin fraction is shown in the Duchenne and congenital muscular dystrophy. The increase in CSF IgG, γ-globulin fraction is shown in the myotonic dystrophy. In addition to the abnormality of IQ, EEG, and brain CT, abnormal CSF proteins obviously suggest the presence of CNS involvement in muscular dystrophy. (author)

  9. CT finding and cerebrospinal fluid proteins in muscular dystrophy patients

    Energy Technology Data Exchange (ETDEWEB)

    Hirase, Tsutomu; Ide, Masami; Araki, Shukuro; Okamoto, Hiroshi (Kumamoto Univ. (Japan). School of Medicine); Kawasaki, Shoichiro; Imamura, Shigehiro

    1983-06-01

    We analyzed the microcomponents of protein fractions in the cerebrospinal fluid of patients with various types of muscular dystrophy. The degenerative pattern is characterized by an increase in the prealbumin and a decrease in the ..gamma..-globulin fraction is shown in the Duchenne and congenital muscular dystrophy. The increase in CSF IgG, ..gamma..-globulin fraction is shown in the myotonic dystrophy. In addition to the abnormality of IQ, EEG, and brain CT, abnormal CSF proteins obviously suggest the presence of CNS involvement in muscular dystrophy.

  10. Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy

    Science.gov (United States)

    Martin, Elizabeth A.; Barresi, Rita; Byrne, Barry J.; Tsimerinov, Evgeny I.; Scott, Bryan L.; Walker, Ashley E.; Gurudevan, Swaminatha V.; Anene, Francine; Elashoff, Robert M.; Thomas, Gail D.; Victor, Ronald G.

    2013-01-01

    Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin’s rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates local α-adrenergic vasoconstriction thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective—causing functional muscle ischemia—in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. Here, we report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled cross-over trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation fully restored in the muscles of men with BMD by boosting NO-cGMP signaling with a single dose of the drug tadalafil, a phosphodiesterase (PDE5A) inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD. PMID:23197572

  11. Dysphagia in Duchenne muscular dystrophy: practical recommendations to guide management.

    Science.gov (United States)

    Toussaint, Michel; Davidson, Zoe; Bouvoie, Veronique; Evenepoel, Nathalie; Haan, Jurn; Soudon, Philippe

    2016-10-01

    Duchenne muscular dystrophy (DMD) is a rapidly progressive neuromuscular disorder causing weakness of the skeletal, respiratory, cardiac and oropharyngeal muscles with up to one third of young men reporting difficulty swallowing (dysphagia). Recent studies on dysphagia in DMD clarify the pathophysiology of swallowing disorders and offer new tools for its assessment but little guidance is available for its management. This paper aims to provide a step-by-step algorithm to facilitate clinical decisions regarding dysphagia management in this patient population. This algorithm is based on 30 years of clinical experience with DMD in a specialised Centre for Neuromuscular Disorders (Inkendaal Rehabilitation Hospital, Belgium) and is supported by literature where available. Dysphagia can worsen the condition of ageing patients with DMD. Apart from the difficulties of chewing and oral fragmentation of the food bolus, dysphagia is rather a consequence of an impairment in the pharyngeal phase of swallowing. By contrast with central neurologic disorders, dysphagia in DMD accompanies solid rather than liquid intake. Symptoms of dysphagia may not be clinically evident; however laryngeal food penetration, accumulation of food residue in the pharynx and/or true laryngeal food aspiration may occur. The prevalence of these issues in DMD is likely underestimated. There is little guidance available for clinicians to manage dysphagia and improve feeding for young men with DMD. This report aims to provide a clinical algorithm to facilitate the diagnosis of dysphagia, to identify the symptoms and to propose practical recommendations to treat dysphagia in the adult DMD population. Implications for Rehabilitation Little guidance is available for the management of dysphagia in Duchenne dystrophy. Food can penetrate the vestibule, accumulate as residue or cause aspiration. We propose recommendations and an algorithm to guide management of dysphagia. Penetration/residue accumulation

  12. Neuroimaging study of Fukuyama type congenital muscular dystrophy

    International Nuclear Information System (INIS)

    Murasugi, Hiroko

    1992-01-01

    Fukuyama type congenital muscular dystrophy (FCMD) has been attracting attention in recent years because of its brain malformation and progressive muscular dystrophy. The intravitam recognition of brain malformation has been remarkably enhanced by the advent of noninvasive neuroimaging techniques such as CT and MRI. In this study, 87 cranial CT scans and 22 MRIs of the brain, carried out on 60 patients with FCMD, were systematically surveyed, and the correlation between neuroradiological findings and clinical disabilities, and, in two autopsy cases, neuropathological findings was evaluated. Four cases of lissencephalic, 29 of pachygyric, and one of polymicrogyric (suspected) brain surface, and 2 normal brain surfaces were recognized. The patients with lissencephalic brain surface were compared using Dobyns' criteria. Grading of pachygyria was judged as bilateral II in 52% of cases and bilateral I in 48%. The surface of the occipital lobe could not be confirmed with either CT or MRI. Polymicrogyria was suspected using MRI but could not confirmed with CT. Five caces of lissencephaly had never learned any meaningful words and all but one were bedridden because of poor head control. The abilities of patients were better when the grading of pachygyria was milder. Mental disability and peak motor function correlate more closely with the degree and extent of brain malformation than with muscle degeneration. The decrease in radiodensity in the white matter was remarkable in 12 out of 19 cases (63%), and was usually bilaterally symmetrical. An increase in radiodensity in the white matter with age was observed in 3 patients. The rate of myelination was slower than normal in 3 out of the 6 cases. (author)

  13. Neuroimaging study of Fukuyama type congenital muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Murasugi, Hiroko (Tokyo Women' s Medical Coll. (Japan))

    1992-11-01

    Fukuyama type congenital muscular dystrophy (FCMD) has been attracting attention in recent years because of its brain malformation and progressive muscular dystrophy. The intravitam recognition of brain malformation has been remarkably enhanced by the advent of noninvasive neuroimaging techniques such as CT and MRI. In this study, 87 cranial CT scans and 22 MRIs of the brain, carried out on 60 patients with FCMD, were systematically surveyed, and the correlation between neuroradiological findings and clinical disabilities, and, in two autopsy cases, neuropathological findings was evaluated. Four cases of lissencephalic, 29 of pachygyric, and one of polymicrogyric (suspected) brain surface, and 2 normal brain surfaces were recognized. The patients with lissencephalic brain surface were compared using Dobyns' criteria. Grading of pachygyria was judged as bilateral II in 52% of cases and bilateral I in 48%. The surface of the occipital lobe could not be confirmed with either CT or MRI. Polymicrogyria was suspected using MRI but could not confirmed with CT. Five caces of lissencephaly had never learned any meaningful words and all but one were bedridden because of poor head control. The abilities of patients were better when the grading of pachygyria was milder. Mental disability and peak motor function correlate more closely with the degree and extent of brain malformation than with muscle degeneration. The decrease in radiodensity in the white matter was remarkable in 12 out of 19 cases (63%), and was usually bilaterally symmetrical. An increase in radiodensity in the white matter with age was observed in 3 patients. The rate of myelination was slower than normal in 3 out of the 6 cases. (author).

  14. Fukuyama type congenital muscular dystrophy with unusual features

    International Nuclear Information System (INIS)

    Mori, Hideo; Oguni, Hirokazu; Osawa, Makiko; Suzuki, Haruko; Fukuyama, Yukio

    1980-01-01

    The Fukuyama type congenital muscular dystrophy (F-CMD) has been generally recognized as a well delineated subgroup of progressive muscular dystrophy (PMD) with uniform clinical, pathological, and genetic features. However, there are still debate to be solved as to the etiology of the condition, because several neuropathological findings found in F-CMD brain allowed some investigators to hypothesize the intrauterine infection to be a primary causation. The authors reported here two families with two affected siblings in each. In the pedigree A, consanguineous parents produced two sisters, Case 1 (3-year-old) and Case 2 (14-month-old). Two patients in the pedigree B, the products of non-consanguineous parents, Case 3 (4-month-old male) and his elder sister already decreased, were affected with F-CMD and infantile spasms. In all cases, generalized weakness and hypotonia had been remarkable since their early infancy, and muscle atrophy, myopathic facies multiple joint contractures and mental dullness became evident gradually. The above-mentioned clinical features as well as laboratory findings including elevated serum CPK and myogenic EMG were compatible with those of typical F-CMD. However, they were characterized by the following three unusual features. 1. Muscle biopsy: In addition to an overwhelming myogenic change, there was a distinct inflammatory cell infiltration in all cases, and scattered small groups of atrophic fibers were present in Case 2. 2. Brain CT scanning: A symmetrical and extensive low density area was observed in the cerebral white matter in all cases. 3. A favorable response to prednisolone therapy was noted in all cases. (author)

  15. Prevalence and correlates of apathy in myotonic dystrophy type 1.

    Science.gov (United States)

    Gallais, Benjamin; Montreuil, Michèle; Gargiulo, Marcela; Eymard, Bruno; Gagnon, Cynthia; Laberge, Luc

    2015-08-22

    Apathy in DM1 has long been acknowledged in clinical practice. However, a major drawback is that the concept has been only sparsely explored in previous specific studies. This study aimed to determine the prevalence of apathy in myotonic dystrophy (DM1), to compare it with facioscapulohumeral dystrophy (FSHD) patients and normal healthy controls, and explore its relationship to psychopathological features and cognitive function. Levels of apathy in 38 DM1 patients with adult phenotypes were compared with 19 patients with FSHD and 20 matched controls. Patient participants were consecutively recruited, regarding their interdisciplinary annual evaluation at the neuromuscular pathology reference center (Institute of Myology, Paris, France), within an 18-month period. Additional measurements included motor disability, fatigue, depression, anxiety, and cognitive abilities. Inter-group comparisons were performed using non-parametric Kruskal-Wallis tests and Mann-Whitney U Tests. Intra-group comparisons were carried out with the Wilcoxon Signed rank and Friedman tests. Also, Spearman's correlations were used to assess the strength of linear relationships between pairs of variables. The significance level was set at 0.05. Global score of apathy was significantly higher in DM1 patients than in FSHD patients (p fatigue, depression, and anxiety. Apathy is a frequent symptom in DM1 (almost 40 %). It is more prevalent than in a similarly disabled group of patients with FSHD and in controls. Results also show that apathy in DM1 is independent of the psychopathological domain, fatigue, age, and motor disability, but associated to general cognitive status. These results altogether could suggest a central cause for apathy in DM1 rather than an adjustment process to cope with the progressive and debilitating nature of the disease. Data emphasize the importance to evaluate this symptom in routine clinical management of DM1 patients.

  16. Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy.

    Science.gov (United States)

    Martin, Elizabeth A; Barresi, Rita; Byrne, Barry J; Tsimerinov, Evgeny I; Scott, Bryan L; Walker, Ashley E; Gurudevan, Swaminatha V; Anene, Francine; Elashoff, Robert M; Thomas, Gail D; Victor, Ronald G

    2012-11-28

    Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.

  17. Radioimmunoassay for human myoglobin: methods and results in patients with skeletal muscle or myocardial disorders. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Miyoshi, K.; Saito, S.; Kawai, H.; Kondo, A.; Iwasa, M.; Hayashi, T.; Yagita, M.

    1978-09-01

    A sensitive and specific radioimmunoassay has been developed for the measurement of serum Mb. Immunization of rabbit with human Mb yielded anti-Mb antibody which was purified by affinity chromatography. Human hemoglobin, CK, and the component of serum per se did not appear to cross-react with the antibody. Mb was radiolabeled by the chloramine T method. The radioimmunoassay method could detect as little as 0.3 ng of Mb and was not affected by hemolysis. Information is also given on precision, recovery, and specimen preservation. Mb levels could be detected in all of 120 normal adults, and the values ranged between 1 and 28 ng/ml (mean, 13.1 +- 6.1). No sex difference was observed. Levels were markedly elevated in all the patients with progressive muscular dystrophy, especially in the Duchenne type at the level of 40 to 1700 ng/ml. It was also noticed that about 70% of female gene carriers of Duchenne type had a slightly increased Mb level. An elevated serum Mb was also noted in polymyositis. In every case of acute myocardial infarction, serum Mb levels were increased, peak values ranging from 175 to 4400 ng/ml and averaging 1162 +- 287.9 Mb levels were elevated faster and peaked earlier (within 6 to 12 hr after the attack) than serum CK activity and returned to nearly normal range within 3 to 4 days. The increase in serum Mb was also noticed in shock and surgery. These data indicate that radioimmunoassay of Mb is a useful test for judging the myolytic state of myogenic myopathies and for early detection of myocardial infarction.

  18. Defective myoblasts identified in Duchenne muscular dystrophy.

    OpenAIRE

    Blau, H M; Webster, C; Pavlath, G K

    1983-01-01

    A defect in the proliferative capacity of satellite cells, mononucleated precursors of mature muscle fibers, was found in clonal analyses of cells cultured from Duchenne muscular dystrophy (DMD) patients. The total yield of myoblasts per gram of muscle biopsy was decreased to 5% of normal. Of the DMD myoblast clones obtained, a large proportion contained a morphological class of flat distended cells that had an increased generation time and ceased to proliferate beyond 100-1,000 cells but cou...

  19. Corneal elastosis within lattice dystrophy lesions.

    Science.gov (United States)

    Pe'er, J; Fine, B S; Dixon, A; Rothberg, D S

    1988-01-01

    Corneal buttons of two patients with lattice corneal dystrophy were studied by light and electron microscopy. They showed elastotic degeneration within the amyloid deposits. The amyloid deposits displayed characteristic staining; the elastotic material (elastin) within the deposits stained positive with Verhoeff-van Gieson and Movat pentachrome stains and showed autofluorescence. The characteristic ultrastructural findings of amyloid and elastotic material were also demonstrated. The possibility of the associations of these two materials in the cornea is discussed. Images PMID:3258531

  20. CONGENITAL MYOTONIC DYSTROPHY – CASE REPORT

    Directory of Open Access Journals (Sweden)

    David Neubauer

    2001-07-01

    Full Text Available Background. Myotonic dystrophy is inherited as an autosomal dominant trait. It is characterized by myotonia, myopathy of voluntary and involuntary muscles, frontal baldness in men, cardiac conduction abnormalities, catharacts, intellectual deterioration and endocrinopathy. Men with this disorder have often gonadal atrophy and infertility. On the other hand women are generally fertile. During pregnancy their myopathy worsens, often causing severe obstetrical complications. Their children may develop congenital form of the disease with signs of myopathy in utero and have great difficulties in maintaining life functions after birth, together with other characteristical signs of this form: bilateral facial weakness, severe hypotonia, feeding difficulties, talipes equinovarus and mental retardation. The authors present a female newborn with such congenital form of myotonic dystrophy.Conclusions. The authors have emphasized the importance of medical history, regular updating of all the cases of neuromuscular diseases in the region and clinical characteristics for the recognition of congenital form of myotonic dystrophy because of possible prenatal diagnostics and better antenatal and postantal care.

  1. Clinical analysis of 155 patients with Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Qi BING

    2015-05-01

    Full Text Available Objective To investigate the clinical manifestations and laboratory examinations of Duchenne muscular dystrophy (DMD patients and evaluate the principle of intermittent intravenous combined with oral glucocorticoid therapy.  Methods The clinical features, laboratory examinations andfollow-up data of 155 DMD patients were collected. These patients were given dexamethasone 5-10 mg/d by intravenous infusion for 10-15 d and oral prednisone acetate 0.50-0.75 mg/(kg·d for one month. After treatment, the motor ability of lower limbs, the level of serum creatine kinase (CK and 99mTc-MIBI gated myocardial perfusion imaging (GMPI findings were compared with those before glucocorticoid therapy by statistical analysis.  Results 1 The motor ability was improved in 70 follow-up cases of DMD patients with long-term oral prednisone (squat and rise: Z = 207.000, P = 0.034; climbing stairs: Z = 237.000, P =0.008. 2 The level of serum CK of 155 first diagnosed patients reached the peak at 3 years old, and declined after the age of 8 (P < 0.05, for all. The serum CK of 70 follow-up cases was significantly decreased after 10-15 d dexamethasone intravenous infusion (P = 0.000, and increased again after one-month oral administration of prednisone acetate (P = 0.000, but was still lower than that before treatment (P = 0.008. 3 The 99mTc-MIBI GMPI of 77 patients showed different degrees of myocardial involvement and significantly uneven left ventricular radionuclide distribution, especially in apex cordis (55 cases, inferior wall (45 cases and anterior wall (30 cases of apex. Conclusions There exists increased level of serum CK in the sub⁃clinical stage of DMD. The level of serum CK declined year by year after the age of 8. Intermittent intravenous combined with oral glucocorticoid therapy has an important effect on protecting motor and cardiac functions, extending walking time and reducing serum CK level and muscle cell damage. Early glucocorticoid therapy is

  2. TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy.

    Science.gov (United States)

    Fiorillo, Alyson A; Heier, Christopher R; Novak, James S; Tully, Christopher B; Brown, Kristy J; Uaesoontrachoon, Kitipong; Vila, Maria C; Ngheim, Peter P; Bello, Luca; Kornegay, Joe N; Angelini, Corrado; Partridge, Terence A; Nagaraju, Kanneboyina; Hoffman, Eric P

    2015-09-08

    The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Alyson A. Fiorillo

    2015-09-01

    Full Text Available The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45–47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31. microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression.

  4. What Can DuchenneConnect Teach Us About Treating Duchenne Muscular Dystrophy?

    Science.gov (United States)

    Wang, Richard T; Nelson, Stanley F

    2015-01-01

    Purpose of Review This review aims to describe the benefits and limitations of using the DuchenneConnect patient registry to provide information particularly in regard to active treatment choices in Duchenne muscular dystrophy and their impact on disease progression. Recent findings Clinical trials and natural history studies are difficult for rare diseases like Duchenne muscular dystrophy. Using an online patient self-report survey model, DuchenneConnect provides relevant data that are difficult to gather in other ways. Validation of the overall dataset is supported by comparable mutational spectrum relative to other cohorts and demonstrated beneficial effect of corticosteroid use in prolonging ambulation. These types of analyses are provocative and allow multivariate analyses across the breadth of patient and physician medication and supplement practices. Because the data is self-reported and online, the barrier to participation is low and great potential exists for novel directions of further research in a highly participatory forum. Summary Patient registries for Duchenne and Becker muscular dystrophy are powerful tools for monitoring patient outcomes, comparing treatments options, and relating information between patients, researchers and clinicians. DuchenneConnect is an online patient self-report registry for individuals with DBMD that facilitates aggregation of treatment modalities, outcomes and genotype data and has played a vital role in furthering DBMD research, particularly in the US, in a highly participatory and low cost manner. PMID:26356412

  5. Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy

    Science.gov (United States)

    Villalta, S. Armando; Rosenthal, Wendy; Martinez, Leonel; Kaur, Amanjot; Sparwasser, Tim; Tidball, James G.; Margeta, Marta; Spencer, Melissa J.; Bluestone, Jeffrey A.

    2016-01-01

    We examined the hypothesis that regulatory T cells (Tregs) modulate muscle injury and inflammation in the mdx mouse model of Duchenne muscular dystrophy (DMD). Although Tregs were largely absent in the muscle of wildtype mice and normal human muscle, they were present in necrotic lesions, displayed an activated phenotype and showed increased expression of interleukin (IL)-10 in dystrophic muscle from mdx mice. Depletion of Tregs exacerbated muscle injury and the severity of muscle inflammation, which was characterized by an enhanced interferon-gamma (IFNγ) response and activation of M1 macrophages. To test the therapeutic value of targeting Tregs in muscular dystrophy, we treated mdx mice with IL-2/anti-IL-2 complexes (IL-2c), and found that Tregs and IL-10 concentrations were increased in muscle, resulting in reduced expression of cyclooygenase-2 and decreased myofiber injury. These findings suggest that Tregs modulate the progression of muscular dystrophy by suppressing type 1 inflammation in muscle associated with muscle fiber injury, and highlight the potential of Treg-modulating agents as therapeutics for DMD. PMID:25320234

  6. What can Duchenne Connect teach us about treating Duchenne muscular dystrophy?

    Science.gov (United States)

    Wang, Richard T; Nelson, Stanley F

    2015-10-01

    This review aims to describe the benefits and limitations of using the Duchenne Connect patient registry to provide information particularly in regard to active treatment choices in Duchenne muscular dystrophy and their impact on disease progression. Clinical trials and natural history studies are difficult for rare diseases like Duchenne muscular dystrophy. Using an online patient self-report survey model, Duchenne Connect provides relevant data that are difficult to gather in other ways. Validation of the overall dataset is supported by comparable mutational spectrum relative to other cohorts and demonstrated beneficial effect of corticosteroid use in prolonging ambulation. These types of analyses are provocative and allow multivariate analyses across the breadth of patient and physician medication and supplement practices. Because the data are self-reported and online, the barrier to participation is low and great potential exists for novel directions of further research in a highly participatory forum. Patient registries for Duchenne and Becker muscular dystrophy (DBMD) are powerful tools for monitoring patient outcomes, comparing treatment options, and relating information between patients, researchers, and clinicians. Duchenne Connect is an online patient self-report registry for individuals with DBMD that facilitates aggregation of treatment modalities, outcomes, and genotype data and has played a vital role in furthering DBMD research, particularly in the USA, in a highly participatory and low-cost manner.

  7. X-rays computed tomographic scans of lower limb and trunk muscles in facioscapulohumeral muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Horikawa, Hirosei; Mano, Yukio; Takayanagi, Tetsuya [Nara Medical Univ., Kashihara (Japan); Takahashi, Keiichi; Nishio, Hisahide

    1992-10-01

    X-rays computed tomographic (CT) scans of muscles of the lower limbs and the trunk in 14 patients with facioscapulohumeral muscular dystrophy (FSH) were studied. The CT scans showed that the affected muscles were decreased in density and size. The laterality of muscular involvement was sometimes observed. The muscular lesions in the lower limbs showed proximal distribution. In the thigh, the hamstrings were affected first, the adductor muscles second, and then the muscular involvement progressed to the quadriceps femoris muscle. In the lower leg, the gastrocnemius and soleus muscles were relatively spared as compared with the tibialis anterior muscle. In the lumbar girdle, the abdominal muscles were involved first, the gluteal muscles second, the back muscles third, and the psoas major muscle were relatively spared. The muscular weakness of this distribution exacerbated lumbar lordosis. The neck muscles were less affected than those of the lumbar girdle. The CT scans in FSH demonstrated the characteristic pattern of muscular involvement, which differed from the inherited muscular diseases such as Duchenne muscular dystrophy, myotonic dystrophy, and others. (author).

  8. X-rays computed tomographic scans of lower limb and trunk muscles in facioscapulohumeral muscular dystrophy

    International Nuclear Information System (INIS)

    Horikawa, Hirosei; Mano, Yukio; Takayanagi, Tetsuya; Takahashi, Keiichi; Nishio, Hisahide.

    1992-01-01

    X-rays computed tomographic (CT) scans of muscles of the lower limbs and the trunk in 14 patients with facioscapulohumeral muscular dystrophy (FSH) were studied. The CT scans showed that the affected muscles were decreased in density and size. The laterality of muscular involvement was sometimes observed. The muscular lesions in the lower limbs showed proximal distribution. In the thigh, the hamstrings were affected first, the adductor muscles second, and then the muscular involvement progressed to the quadriceps femoris muscle. In the lower leg, the gastrocnemius and soleus muscles were relatively spared as compared with the tibialis anterior muscle. In the lumbar girdle, the abdominal muscles were involved first, the gluteal muscles second, the back muscles third, and the psoas major muscle were relatively spared. The muscular weakness of this distribution exacerbated lumbar lordosis. The neck muscles were less affected than those of the lumbar girdle. The CT scans in FSH demonstrated the characteristic pattern of muscular involvement, which differed from the inherited muscular diseases such as Duchenne muscular dystrophy, myotonic dystrophy, and others. (author)

  9. Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Dandan Tan

    Full Text Available This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA-related muscular dystrophy (MD. The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293 cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD. Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.

  10. From proteins to genes: immunoanalysis in the diagnosis of muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Barresi Rita

    2011-06-01

    Full Text Available Abstract Muscular dystrophies are a large heterogeneous group of inherited diseases that cause progressive muscle weakness and permanent muscle damage. Very few muscular dystrophies show sufficient specific clinical features to allow a definite diagnosis. Because of the currently limited capacity to screen for numerous genes simultaneously, muscle biopsy is a time and cost-effective test for many of these disorders. Protein analysis interpreted in correlation with the clinical phenotype is a useful way of directing genetic testing in many types of muscular dystrophies. Immunohistochemistry and western blot are complementary techniques used to gather quantitative and qualitative information on the expression of proteins involved in this group of diseases. Immunoanalysis has a major diagnostic application mostly in recessive conditions where the absence of labelling for a particular protein is likely to indicate a defect in that gene. However, abnormalities in protein expression can vary from absence to very subtle reduction. It is good practice to test muscle biopsies with antibodies for several proteins simultaneously and to interpret the results in context. Indeed, there is a degree of direct or functional association between many of these proteins that is reflected by the presence of specific secondary abnormalities that are of value, especially when the diagnosis is not straightforward.

  11. Assessment of left ventricular regional function in affected and carrier dogs with duchenne muscular dystrophy using speckle tracking echocardiography

    Directory of Open Access Journals (Sweden)

    Yugeta Naoko

    2011-05-01

    Full Text Available Abstract Background Two-dimensional speckle tracking echocardiography (STE is a relatively new method to detect regional myocardial dysfunction. To assess left ventricular (LV regional myocardial dysfunction using STE in Duchenne muscular dystrophy model dogs (CXMDJ without overt clinical signs of heart failure. Methods Six affected dogs, 8 carrier dogs with CXMDJ, and 8 control dogs were used. Conventional echocardiography, systolic and diastolic function by Doppler echocardiography, tissue Doppler imaging (TDI, and strain indices using STE, were assessed and compared among the 3 groups. Results Significant differences were seen in body weight, transmitral E wave and E' wave derived from TDI among the 3 groups. Although no significant difference was observed in any global strain indices, in segmental analysis, the peak radial strain rate during early diastole in posterior segment at chordae the tendineae level showed significant differences among the 3 groups. Conclusions The myocardial strain rate by STE served to detect the impaired cardiac diastolic function in CXMDJ without any obvious LV dilation or clinical signs. The radial strain rate may be a useful parameter to detect early myocardial impairment in CXMDJ.

  12. [Principles of multidisciplinary management of Duchenne muscular dystrophy].

    Science.gov (United States)

    Chabrol, B; Mayer, M

    2015-12-01

    Given the gradual progression observed in Duchenne muscular dystrophy, organization of care in multidisciplinary consultations is essential for optimal management of the different aspects of the disease. Drawing up a care plan is always preceded by a specific consultation for the announcement of the diagnosis with both the parents and the child. Explaining to the child the origin of his problems with simple words, telling him that why he experienced a particular symptom has been understood, is a fundamental step. The child needs to receive the information at different times of the disease following the rhythms of the disease stages, with an appropriate lead time. With the progress achieved in managing this disease, more than 90% of these children now live into adulthood. The switch from pediatric consultations to adult consultations, marking the transition from childhood management at adulthood, is a major challenge in the organization of care. Although today death occurs most often in adulthood, some children die in childhood. For the majority of teams who care for children, whatever the initial pathology may be, the notion of care continuity and accompaniment from the announcement of the disease to the terminal phase is essential. Increasing numbers of therapeutic trials have been developed over the past few years aiming to investigate children with DMD. However, they must not neglect the overall management of these patients and provide the best accompaniment possible. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. Health-related quality of life and its relation to disease severity in boys with Duchenne muscular dystrophy: satisfied boys, worrying parents--a case-control study

    NARCIS (Netherlands)

    Houwen-van Opstal, S.L.; Jansen, M.; Alfen, N. van; Groot, I.J.M. de

    2014-01-01

    The progression of Duchenne muscular dystrophy is expected to negatively influence the patients' health-related quality of life, but knowledge of the relationship with disease severity is limited. We investigated the relationship between health-related quality of life (KIDSCREEN-52 questionnaire)

  14. Feasibility of SPECT-CT imaging to study the pharmacokinetics of antisense oligonucleotides in a mouse model of Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Steeg, E. van de; Läppchen, T.; Aguilera, B.; Jansen, H.T.; Muilwijk, D.; Vermue, R.; Hoorn, J.W. van der; Donato, K.; Rossin, R.; Visser, P.C. de; Vlaming, M.L.H.

    2017-01-01

    Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic.

  15. Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations

    Directory of Open Access Journals (Sweden)

    Oriana del Rocío Cruz Guzmán

    2012-01-01

    Full Text Available Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset.

  16. Upper limb function in adults with Duchenne muscular dystrophy

    NARCIS (Netherlands)

    B. Bartels (Bart); R.F. Pangalila (Robert); M.P. Bergen (Michael); N.A.M. Cobben (Nicolle); H.J. Stam (Henk); M.E. Roebroeck (Marij)

    2011-01-01

    textabstractTo determine upper limb function and associated factors in adults with Duchenne muscular dystrophy. Design: Cross-sectional study. Subjects: A sample of 70 men with Duchenne muscular dystrophy (age range 20-43 years). Methods: General motor function and, in particular, upper limb distal

  17. Dysphagia is present but mild in myotonic dystrophy type 2

    NARCIS (Netherlands)

    R. Ensink; Bert de Swart; J. van Vliet; A. Tieleman; Baziel van Engelen; S. Knuijt

    2009-01-01

    The phenotype of myotonic dystrophy type 2 (DM2) shows similarities as well as differences to that of myotonic dystrophy type 1 (DM1). Dysphagia, a predominant feature in DM1, has not yet been examined in DM2. In a recent nationwide questionnaire survey of gastrointestinal symptoms in DM2, 12 out of

  18. Limb girdle muscular dystrophy due to mutations in POMT2

    DEFF Research Database (Denmark)

    Østergaard, Sofie Thurø; Johnson, Katherine; Stojkovic, Tanya

    2018-01-01

    BACKGROUND: Mutations in the gene coding for protein O-mannosyl-transferase 2 (POMT2) are known to cause severe congenital muscular dystrophy, and recently, mutations in POMT2 have also been linked to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four...

  19. Further delineation of spondylometaphyseal dysplasia with cone-rod dystrophy

    NARCIS (Netherlands)

    Sousa, Sérgio B.; Russell-Eggitt, Isabelle; Hall, Christine; Hall, Bryan D.; Hennekam, Raoul C. M.

    2008-01-01

    There are several entities that combine a skeletal dysplasia with a retinal dystrophy. Recently, another possibly autosomal recessive entity was added to this group characterized by a specific spondylometaphyseal dysplasia and a cone-rod dystrophy, without other significant impairments. The entity

  20. [Ocular findings in patients with Steinert myotonic dystrophy].

    Science.gov (United States)

    Markowska, Elzbieta; Zalewska, Renata; Mariak, Zofia; Wojnar, Małgorzata

    2006-01-01

    The authors present one of many myotonic dystrophies: Steinert myotonic dystrophy (Steinert disease), which is a disease occuring seldom, and causing a lot of problems during the diagnostic and treatment process. Genetic factors, results of the histopathology tests, main clinical symptoms, particularly ophtalmic manifestation are described in this article.

  1. Central areolar choroidal dystrophy with associated dominant drusen

    Directory of Open Access Journals (Sweden)

    Julie Rodman

    2013-04-01

    Conclusion: Central areolar choroidal dystrophy normally presents without drusen. However, in patients manifesting a specific mutation, central areolar choridal dystrophy may present in conjunction with drusen. It appears that the Arg142Trp mutation is one of the factors predisposing to drusen formation.

  2. An herbal medicine, Go-sha-jinki-gan (GJG, increases muscle weight in severe muscle dystrophy model mice

    Directory of Open Access Journals (Sweden)

    Yusei Takemoto

    2017-12-01

    Full Text Available Go-sha-jinki-gan (GJG, a traditional Japanese herbal medicine has a clinical implication to alleviate age-related symptoms, especially in some motor disorders. However, the scientific evidence is limited, and there is a possibility to expand the medical application range of GJG. Using senescence-accelerated mice, our group showed that GJG exerted an effect to prevent sarcopenia, the aged-related loss of skeletal muscle. Because muscular dystrophy is characterized by a progressive loss of skeletal muscle, we examined the effects of GJG on a mouse model of muscular dystrophy. Using a newly established mouse model for Duchenne muscular dystrophy (DMD, DBA/2-mdx, we showed that GJG significantly increased the body and skeletal muscle weights in comparison to the control DBA/2-mdx mice, regardless of gender. The increased skeletal muscle mass resulted from an increment in the myofiber size, but not from the myofiber number. Both the skeletal muscle regenerative ability and the accumulation of fibrosis (the dystrophic pathology in GJG-fed DBA/2-mdx mice were comparable to those in control DBA/2-mdx mice, suggesting that the cellular target of GJG is myofibers, with no contribution from the muscle satellite cells neither in an direct nor in an indirect manner. Taken together, GJG increased the skeletal muscle mass in a mouse model of muscular dystrophy, in addition to our previously tested sarcopenia mouse model.

  3. Reliability, validity and description of timed performance of the Jebsen-Taylor Test in patients with muscular dystrophies.

    Science.gov (United States)

    Artilheiro, Mariana Cunha; Fávero, Francis Meire; Caromano, Fátima Aparecida; Oliveira, Acary de Souza Bulle; Carvas, Nelson; Voos, Mariana Callil; Sá, Cristina Dos Santos Cardoso de

    2017-12-08

    The Jebsen-Taylor Test evaluates upper limb function by measuring timed performance on everyday activities. The test is used to assess and monitor the progression of patients with Parkinson disease, cerebral palsy, stroke and brain injury. To analyze the reliability, internal consistency and validity of the Jebsen-Taylor Test in people with Muscular Dystrophy and to describe and classify upper limb timed performance of people with Muscular Dystrophy. Fifty patients with Muscular Dystrophy were assessed. Non-dominant and dominant upper limb performances on the Jebsen-Taylor Test were filmed. Two raters evaluated timed performance for inter-rater reliability analysis. Test-retest reliability was investigated by using intraclass correlation coefficients. Internal consistency was assessed using the Cronbach alpha. Construct validity was conducted by comparing the Jebsen-Taylor Test with the Performance of Upper Limb. The internal consistency of Jebsen-Taylor Test was good (Cronbach's α=0.98). A very high inter-rater reliability (0.903-0.999), except for writing with an Intraclass correlation coefficient of 0.772-1.000. Strong correlations between the Jebsen-Taylor Test and the Performance of Upper Limb Module were found (rho=-0.712). The Jebsen-Taylor Test is a reliable and valid measure of timed performance for people with Muscular Dystrophy. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

  4. PAI-1–regulated miR-21 defines a novel age-associated fibrogenic pathway in muscular dystrophy

    Science.gov (United States)

    Ardite, Esther; Perdiguero, Eusebio; Vidal, Berta; Gutarra, Susana; Serrano, Antonio L.

    2012-01-01

    Disruption of skeletal muscle homeostasis by substitution with fibrotic tissue constitutes the principal cause of death in Duchenne muscular dystrophy (DMD) patients, yet the implicated fibrogenic mechanisms remain poorly understood. This study identifies the extracellular PAI-1/urokinase-type plasminogen activator (uPA) balance as an important regulator of microribonucleic acid (miR)–21 biogenesis, controlling age-associated muscle fibrosis and dystrophy progression. Genetic loss of PAI-1 in mdx dystrophic mice anticipated muscle fibrosis through these sequential mechanisms: the alteration of collagen metabolism by uPA-mediated proteolytic processing of transforming growth factor (TGF)–β in muscle fibroblasts and the activation of miR-21 expression, which inhibited phosphatase and tensin homologue and enhanced AKT signaling, thus endowing TGF-β with a remarkable cell proliferation–promoting potential. Age-associated fibrogenesis and muscle deterioration in mdx mice, as well as exacerbated dystrophy in young PAI-1−/− mdx mice, could be reversed by miR-21 or uPA-selective interference, whereas forced miR-21 overexpression aggravated disease severity. The PAI-1–miR-21 fibrogenic axis also appeared dysregulated in muscle of DMD patients, providing a basis for effectively targeting fibrosis and muscular dystrophies in currently untreatable individuals. PMID:22213800

  5. Resistance training in patients with limb-girdle and becker muscular dystrophies

    DEFF Research Database (Denmark)

    Sveen, Marie-Louise; Andersen, Søren P; Ingelsrud, Lina H

    2013-01-01

    In this study we investigated the effect of strength training in patients with limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy (BMD).......In this study we investigated the effect of strength training in patients with limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy (BMD)....

  6. Granular corneal dystrophy Groenouw type I (GrI) and Reis-Bücklers' corneal dystrophy (R-B). One entity?

    Science.gov (United States)

    Møller, H U

    1989-12-01

    This paper maintains that Reis-Bücklers' corneal dystrophy and granular corneal dystrophy Groenouw type I are one and the same disease. Included are some of the technically best photographs of Reis-Bücklers' dystrophy found in the literature, and these are compared with photographs from patients with granular corneal dystrophy examined by the author. It is argued that most of the histological and ultrastructural findings on Reis Bücklers' dystrophy described in the literature are either congruent with what is found in granular corneal dystrophy or unspecific.

  7. Periodontitis and myocardial hypertrophy.

    Science.gov (United States)

    Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

    2017-04-01

    There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

  8. A comparison of swallowing dysfunction in Becker muscular dystrophy and Duchenne muscular dystrophy.

    Science.gov (United States)

    Yamada, Yuka; Kawakami, Michiyuki; Wada, Ayako; Otsuka, Tomoyoshi; Muraoka, Kaori; Liu, Meigen

    2018-06-01

    Swallowing dysfunction has been reported in Duchenne muscular dystrophy (DMD), but has not been studied in Becker muscular dystrophy (BMD). The aims of this study were to report the characteristics of swallowing dysfunction in BMD compared with DMD. The study participants were 18 patients with BMD and 18 patients with DMD. All the patients were examined using videofluorography during swallowing of 5 mL of fluid. The penetration-aspiration scale (P-A scale) and the videofluorographic dysphagia scale (VDS) were used to evaluate dysphagia. Swinyard functional ability stage was not significantly different between the BMD and DMD groups. Rate of aspiration, P-A scale score, and total VDS score did not differ across groups, but the VDS item score for laryngeal elevation was lower in the BMD group than in the DMD group (median scores 4.5 and 9, respectively; p Becker muscular dystrophy (BMD) was not well known. Eighteen patients with BMD and 18 patients with Duchenne muscular dystrophy were examined with videofluorography. Patients with BMD have swallowing problems similar to those observed in patients with DMD.

  9. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands : a cohort study

    NARCIS (Netherlands)

    Hoogerwaard, EM; Bakker, E; Ippel, PF; Oosterwijk, JC; Majoor-Krakauer, DF; Leschot, NJ; Van Essen, AJ; Brunner, HG; van der Wouw, PA; Wilde, AAM; de Visser, Marianne

    1999-01-01

    Background Carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) may show muscle weakness or dilated cardiomyopathy. Studies focusing on skeletal-muscle involvement were done before DNA analysis was possible. We undertook a cross-sectional study in a population of

  10. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study

    NARCIS (Netherlands)

    Hoogerwaard, E. M.; Bakker, E.; Ippel, P. F.; Oosterwijk, J. C.; Majoor-Krakauer, D. F.; Leschot, N. J.; van Essen, A. J.; Brunner, H. G.; van der Wouw, P. A.; Wilde, A. A.; de Visser, M.

    1999-01-01

    BACKGROUND: Carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) may show muscle weakness or dilated cardiomyopathy. Studies focusing on skeletal-muscle involvement were done before DNA analysis was possible. We undertook a cross-sectional study in a population of

  11. Psychiatric disorders appear equally in patients with myotonic dystrophy, facioscapulohumeral dystrophy, and hereditary motor and sensory neuropathy type I.

    NARCIS (Netherlands)

    Kalkman, J.S.; Schillings, M.L.; Zwarts, M.J.; Engelen, B.G.M. van; Bleijenberg, G.

    2007-01-01

    OBJECTIVES: To study the presence of psychiatric comorbidity assessed by the use of a structured clinical interview and self-reported questionnaires in a large sample of patients with adult-onset myotonic dystrophy (DM), facioscapulohumeral muscular dystrophy (FSHD), and hereditary motor and sensory

  12. Cytogenetic analysis and response to ionizing radiations in a girl with severe muscular dystrophy

    International Nuclear Information System (INIS)

    Meola, G.; Barsi, L.; Velicogna, M.; Scarlato, G.; Fuhrman-Conti, A.M.

    1988-01-01

    Duchenne Muscular Dystrophy (DMD) is a severe X-linked condition characterized by a progressive degeneration of skeletal muscle. Mild clinical symptoms have been reported in female carriers of the DMD gene with normal karyotypes, this occurs in about 8% of DMD carriers. The degree of manifestation ranges from pseudohypertrophy of the calf muscles to moderate myopathy with proximal muscle wasting and weakness. Such manifestations can be explained on the basis of preferential inactivation of the X chromosome bearing the normal allele. The authors describe the cytogenetic analysis and the response to ionizing radiations in a severely affected girl exhibiting clinical, neurophysiological, biochemical, and histological findings of DMD

  13. Metabogenic and Nutriceutical Approaches to Address Energy Dysregulation and Skeletal Muscle Wasting in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Emma Rybalka

    2015-11-01

    Full Text Available Duchenne Muscular Dystrophy (DMD is a fatal genetic muscle wasting disease with no current cure. A prominent, yet poorly treated feature of dystrophic muscle is the dysregulation of energy homeostasis which may be associated with intrinsic defects in key energy systems and promote muscle wasting. As such, supplementative nutriceuticals that target and augment the bioenergetical expansion of the metabolic pathways involved in cellular energy production have been widely investigated for their therapeutic efficacy in the treatment of DMD. We describe the metabolic nuances of dystrophin-deficient skeletal muscle and review the potential of various metabogenic and nutriceutical compounds to ameliorate the pathological and clinical progression of the disease.

  14. Congenital muscular dystrophies--problems of classification.

    Science.gov (United States)

    Lenard, H G

    1991-04-01

    The classification of congenital muscular dystrophies (CMD), based on perceived clinical and morphological similarities or differences, is controversial. CMD without cerebral involvement has sometimes been divided into a mild and a severe form. This distinction is, however, arbitrary and not uncontested. Whether Ullrich's disease, formerly called atonic-sclerotic dystrophy, is a disease entity and if so, whether it is a primary muscle disorder, is uncertain. CMD without cerebral involvement is inherited in an autosomal recessive fashion in the great majority of cases. CMDs with cerebral involvement are usually classified into at least three forms: the Fukuyama type of CMD, occurring almost exclusively in Japanese patients; CMD with hypomyelination, sometimes also called the occidental type of cerebromuscular dystrophy; and Walker-Warburg syndrome. Muscle-eye-brain disease, described in a number of Finnish patients, may or may not belong in this last category. In CMD with cerebral involvement inheritance is also autosomal recessive. It is possible that single sporadic cases are phenocopies due to infectious or other exogenous causes. Reports of clinical and morphological findings from an increasing number of patients show a high degree of variability within and, on the other hand, certain similarities between the forms of CMD with cerebral involvement. In addition, neuroradiological changes are also found with increasing frequency in CMD patients without clinical neuropsychological abnormalities. It is not unreasonable to speculate that molecular genetic techniques will reveal in the near future a variable defect in one gene locus or defects in a few gene loci as the cause of the various clinical forms of CMDs.

  15. Klotho gene silencing promotes pathology in the mdx mouse model of Duchenne muscular dystrophy

    Science.gov (United States)

    Wehling-Henricks, Michelle; Li, Zhenzhi; Lindsey, Catherine; Wang, Ying; Welc, Steven S.; Ramos, Julian N.; Khanlou, Négar; Kuro-o, Makoto; Tidball, James G.

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a lethal muscle disease involving progressive loss of muscle regenerative capacity and increased fibrosis. We tested whether epigenetic silencing of the klotho gene occurs in the mdx mouse model of DMD and whether klotho silencing is an important feature of the disease. Our findings show that klotho undergoes muscle-specific silencing at the acute onset of mdx pathology. Klotho experiences increased methylation of CpG sites in its promoter region, which is associated with gene silencing, and increases in a repressive histone mark, H3K9me2. Expression of a klotho transgene in mdx mice restored their longevity, reduced muscle wasting, improved function and greatly increased the pool of muscle-resident stem cells required for regeneration. Reductions of fibrosis in late, progressive stages of the mdx pathology achieved by transgene expression were paralleled by reduced expression of Wnt target genes (axin-2), transforming growth factor-beta (TGF-β1) and collagens types 1 and 3, indicating that Klotho inhibition of the profibrotic Wnt/TGFβ axis underlies its anti-fibrotic effect in aging, dystrophic muscle. Thus, epigenetic silencing of klotho during muscular dystrophy contributes substantially to lost regenerative capacity and increased fibrosis of dystrophic muscle during late progressive stages of the disease. PMID:27154199

  16. A neonate with congenital myotonic dystrophy

    International Nuclear Information System (INIS)

    Itani, Yasufumi; Anbo, Kazutoshi; Kashiwagi, Sigeru; Yokoya, Susumu; Kato, Kazuo

    1984-01-01

    A boy's neonate with congenital myotonic dystrophy who had difficulty in breathing immediately after birth was reported. A long-term management for artificial breathing was required because of a marked decrease of muscular tone, equinus and the difficulty in sucking milk. Myogenic pattern was seen on EMG and atrophied type I fibers and increased number of type 2 C fibers suggesting the prolongation of differentiation of muscle fibers were seen by muscle biopsy. Cranial CT revealed a marked atrophy of the cerebral cortex and low density area in the white matter, although the latter disappeared 4 months later. (Namekawa, K.)

  17. [Complete atrioventricular block in Duchenne muscular dystrophy].

    Science.gov (United States)

    Kuru, Satoshi; Tanahashi, Tamotsu; Matsumoto, Shinjirou; Kitamura, Tetsuya; Konagaya, Masaaki

    2012-01-01

    We report a case of complete atrioventricular (AV) block in a 40-year-old patient with Duchenne muscular dystrophy (DMD). While he was bed-ridden and required mechanical ventilation, his cardiac involvement was mild. He had the deletion of exon 45-52 in the dystrophin gene. He underwent transient complete AV block and came to require pacemaker implantation due to recurrence of complete AV block ten days after the first attack. Electrophysiological study revealed mild prolonged AH and HV interval. Although DMD patients with AV block have been rarely reported so far, attention should be paid to AV block for patients who prolonged their lives.

  18. Merosin/laminin-2 and muscular dystrophy

    DEFF Research Database (Denmark)

    Wewer, U M; Engvall, E

    1996-01-01

    structural organization of domains, some of which have been assigned biological activities, including self-assembly and interactions with other proteins. The particular importance of laminins for the formation and stability of cell adhesion complexes is highlighted in severe inherited diseases of muscle...... and skin. Merosin is the collective name for laminins that share a common subunit, the laminin alpha 2 chain. Merosin-deficient congenital muscular dystrophy (CMD) is caused by mutations in the laminin alpha 2 chain gene. The skin disease Herlitz junctional epidermolysis bullosa is caused by mutations...

  19. Psychometric properties of the Zarit Caregiver Burden Interview administered to caregivers to patients with Duchenne muscular dystrophy: a Rasch analysis.

    Science.gov (United States)

    Landfeldt, Erik; Mayhew, Anna; Straub, Volker; Bushby, Katharine; Lochmüller, Hanns; Lindgren, Peter

    2017-12-18

    To explore the psychometric properties of the full 22-item English (UK and US) version of the Zarit Caregiver Burden Interview administered to caregivers to patients with Duchenne muscular dystrophy. Caregivers to patients with Duchenne muscular dystrophy from the United Kingdom and the United States, recruited through the TREAT-NMD network, completed the Zarit Caregiver Burden Interview online. The psychometric properties of the Zarit Caregiver Burden Interview were examined using Rasch analysis. A total of 475 caregivers completed the Zarit Caregiver Burden Interview. Model misfit was identified for 9 of 22 items (mean item fit residual 0.061, SD: 2.736) and 13 of 22 items displayed disordered thresholds. The overall item-trait interaction chi-square value was 499 (198 degrees of freedom, p Interview fails to fully operationalize a quantitative conceptualization of caregiver burden among caregivers to patients with Duchenne muscular dystrophy from the United Kingdom and the United States. Further research is needed to understand the psychometric properties of the Zarit Caregiver Burden Interview in other populations and settings. Implications for Rehabilitation Duchenne muscular dystrophy is a terminal disease characterized by progressive muscle degeneration resulting in substantial disability and a significant burden on family caregivers. The Zarit Caregiver Burden Interview is one of the most widely applied measures of caregiver burden. Our Rasch analysis suggests that the Zarit Caregiver Burden Interview is not fit for purpose to measure burden in UK and US caregivers to patients with Duchenne muscular dystrophy. Clinicians and decision-makers should interpret Zarit Caregiver Burden Interview data from these populations with caution.

  20. Survey of Canadian Myotonic Dystrophy Patients' Access to Computer Technology.

    Science.gov (United States)

    Climans, Seth A; Piechowicz, Christine; Koopman, Wilma J; Venance, Shannon L

    2017-09-01

    Myotonic dystrophy type 1 is an autosomal dominant condition affecting distal hand strength, energy, and cognition. Increasingly, patients and families are seeking information online. An online neuromuscular patient portal under development can help patients access resources and interact with each other regardless of location. It is unknown how individuals living with myotonic dystrophy interact with technology and whether barriers to access exist. We aimed to characterize technology use among participants with myotonic dystrophy and to determine whether there is interest in a patient portal. Surveys were mailed to 156 participants with myotonic dystrophy type 1 registered with the Canadian Neuromuscular Disease Registry. Seventy-five participants (60% female) responded; almost half were younger than 46 years. Most (84%) used the internet; almost half of the responders (47%) used social media. The complexity and cost of technology were commonly cited reasons not to use technology. The majority of responders (76%) were interested in a myotonic dystrophy patient portal. Patients in a Canada-wide registry of myotonic dystrophy have access to and use technology such as computers and mobile phones. These patients expressed interest in a portal that would provide them with an opportunity to network with others with myotonic dystrophy and to access information about the disease.

  1. Application of the International Classification of Functioning, Disability and Health system to symptoms of the Duchenne and Becker muscular dystrophies.

    Science.gov (United States)

    Conway, Kristin M; Ciafaloni, Emma; Matthews, Dennis; Westfield, Chris; James, Kathy; Paramsothy, Pangaja; Romitti, Paul A

    2018-07-01

    Duchenne and Becker muscular dystrophies, collectively referred to as dystrophinopathies, are X-linked recessive diseases that affect dystrophin production resulting in compromised muscle function across multiple systems. The International Classification of Functioning, Disability and Health provides a systematic classification scheme from which body functions affected by a dystrophinopathy can be identified and used to examine functional health. The infrastructure of the Muscular Dystrophy Surveillance, Tracking, and Research Network was used to identify commonly affected body functions and link selected functions to clinical surveillance data collected through medical record abstraction. Seventy-one (24 second-, 41 third- and 7 fourth-level) body function categories were selected via clinician review and consensus. Of these, 15 of 24 retained second-level categories were linked to data elements from the Muscular Dystrophy Surveillance, Tracking, and Research Network surveillance database. Our findings support continued development of a core set of body functions from the International Classification of Functioning, Disability and Health system that are representative of disease progression in dystrophinopathies and the incorporation of these functions in standardized evaluations of functional health and implementation of individualized rehabilitation care plans. Implications for Rehabilitation Duchenne and Becker muscular dystrophies, collectively referred to as dystrophinopathies, are X-linked recessive disorders that affect the production of dystrophin resulting in compromised muscle function across multiple systems. The severity and progressive nature of dystrophinopathies can have considerable impact on a patient's participation in activities across multiple life domains. Our findings support continued development of an International Classification of Functioning, Disability and Health core set for childhood-onset dystrophinopathies. A standardized

  2. Balance outcomes following a tap dance program for a child with congenital myotonic muscular dystrophy.

    Science.gov (United States)

    Biricocchi, Charlanne; Drake, JaimeLynn; Svien, Lana

    2014-01-01

    This case report describes the effects of a 6-week progressive tap dance program on static and dynamic balance for a child with type 1 congenital myotonic muscular dystrophy (congenital MMD1). A 6-year-old girl with congenital MMD1 participated in a 1-hour progressive tap dance program. Classes were held once a week for 6 consecutive weeks and included 3 children with adaptive needs and 1 peer with typical development. The Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2) balance subsection and the Pediatric Balance Scale were completed at the beginning of the first class and the sixth class. The participant's BOT-2 score improved from 3 to 14. Her Pediatric Balance Scale score did not change. Participation in a progressive tap dance class by a child with congenital MMD1 may facilitate improvements in static and dynamic balance.

  3. Genetics and emerging treatments for Duchenne and Becker muscular dystrophy.

    Science.gov (United States)

    Wein, Nicolas; Alfano, Lindsay; Flanigan, Kevin M

    2015-06-01

    Mutations in the DMD gene result in Duchenne or Becker muscular dystrophy due to absent or altered expression of the dystrophin protein. The more severe Duchenne muscular dystrophy typically presents around ages 2 to 5 with gait disturbance, and historically has led to the loss of ambulation by age 12. It is important for the practicing pediatrician, however, to be aware of other presenting signs, such as delayed motor or cognitive milestones, or elevated serum transaminases. Becker muscular dystrophy is milder, often presenting after age 5, with ambulation frequently preserved past 20 years and sometimes into late decades. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. MR imaging of fukuyama congenital muscular dystrophy; a case report

    International Nuclear Information System (INIS)

    Yoo, Jeong Hyun; Kim, Yoo Kyung; Koo, Hae Soo; Park, Ki Deuk

    2000-01-01

    Fukuyama congenital muscular dystrophy is a genetic disease and common in Japan. The typical clinical features are hypotonia with an early infantile onset and severe developmental delay. The diagnosis is based on pathologic evidence of muscular dystrophy revealed by biopsy or an increased serum creatine kinase levels. Involvement of the brain is characterized by abnormal cerebral cortical dysplasia, cerebellar dysplasia, and white matter changes. We encountered a case of Fukuyama congenital muscular dystrophy in which brain MRI findings were typical, and present this case together with a review of the literature

  5. Severe metabolic acidosis in adult patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Lo Cascio, Christian M; Latshang, Tsogyal D; Kohler, Malcolm; Fehr, Thomas; Bloch, Konrad E

    2014-01-01

    Duchenne muscular dystrophy (DMD) leads to progressive paresis, respiratory failure and premature death. Long-term positive pressure ventilation can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of severe metabolic acidosis occurring in 8 of 55 DMD patients, of 20-36 years of age, observed over a 5-year period. All patients were on positive pressure ventilation and were being treated for chronic constipation. Before admission, they had had a reduced intake of fluids and food. Upon examination, they were severely ill, dyspneic and suffering from abdominal discomfort. Metabolic acidosis with a high anion gap was noted in 5 of the 8 patients and with a normal anion gap in the other 3. They all recovered after the administration of fluids and nutrition, the regulation of bowel movements and treatment with antibiotics, as appropriate. Metabolic acidosis is a life-threatening, potentially preventable complication in older DMD patients. Early recognition, subsequent administration of fluids, nutrition and antibiotics and regulation of bowel movements seem to be essential. © 2014 S. Karger AG, Basel.

  6. Quantitative electromyography in ambulatory boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    Verma, Sumit; Lin, Jenny; Travers, Curtis; McCracken, Courtney; Shah, Durga

    2017-12-01

    This study's objective was to evaluate quantitative electromyography (QEMG) using multiple-motor-unit (multi-MUP) analysis in Duchenne muscular dystrophy (DMD). Ambulatory DMD boys, aged 5-15 years, were evaluated with QEMG at 6-month intervals over 14 months. EMG was performed in the right biceps brachii (BB) and tibialis anterior (TA) muscles. Normative QEMG data were obtained from age-matched healthy boys. Wilcoxon signed-rank tests were performed. Eighteen DMD subjects were enrolled, with a median age of 7 (interquartile range 7-10) years. Six-month evaluations were performed on 14 subjects. QEMG showed significantly abnormal mean MUP duration in BB and TA muscles, with no significant change over 6 months. QEMG is a sensitive electrophysiological marker of myopathy in DMD. Preliminary data do not reflect a significant change in MUP parameters over a 6-month interval; long-term follow-up QEMG studies are needed to understand its role as a biomarker for disease progression. Muscle Nerve 56: 1361-1364, 2017. © 2017 Wiley Periodicals, Inc.

  7. T2 relaxometry of brain in myotonic dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Di Costanzo, A.; Bonavita, V.; Tedeschi, G. [Inst. of Neurological Sciences, 2. Univ. of Naples (Italy); Di Salle, F. [Dept. of Biomorphological and Functional Sciences, Univ. ' ' Federico II' ' , Naples (Italy); Santoro, L. [Dept. of Neurological Sciences, University ' ' Federico II' ' , Naples (Italy)

    2001-03-01

    We investigated the nature and extent of brain involvement in myotonic dystrophy (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was performed at 0.5 T, and T2 values were calculated from signal intensity in two echoes. Regions of interest included: frontal, parietal, temporal, occipital and callosal (rostral and splenial) normal-appearing white matter; frontal, occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus pallidus and thalamus. All white-matter and occipital and right frontal cortex regions showed a significantly longer T2 in the patients. Multiple regression analysis, including grey- and white-matter T2 as dependent variables, plus age at onset and at imaging, disease duration, muscular disability, brain atrophy and CTG trinucleotide repeats as independent variables, revealed that only white-matter T2 elongation and disease duration correlated positively. White-matter involvement in DM is more extensive than previously reported by MRI and neuropathological studies and seems to be progressive in the course of disease. (orig.)

  8. Punctiform and Polychromatophilic Dominant Pre-Descemet Corneal Dystrophy.

    Science.gov (United States)

    Lagrou, Lisa; Midgley, Julian; Romanchuk, Kenneth Gerald

    2016-04-01

    To describe the slit-lamp appearance and corneal confocal microscopy of autosomal dominant punctiform and polychromatophilic pre-Descemet corneal dystrophy in 3 members of the same family. Slit-lamp examination of a 9-year-old boy showed bilateral polychromatophilic corneal opacities in a pre-Descemet membrane location evenly deposited limbus to limbus, both horizontally and vertically, with an intervening clear cornea. The corneal endothelium was normal on corneal confocal microscopy, with hyperreflective opacities of various sizes located pre-Descemet membrane. Slit-lamp examination of the patient's father and brother revealed identical crystalline deposition in the pre-Descemet corneal stroma. The remainders of the eye examinations were otherwise normal in all 3 individuals, and all were asymptomatic. The general physical examination and laboratory investigations of the patient were all normal, as were the laboratory investigations of the other 2 family members. There was no progression in the corneal findings over 6 months of follow-up. These patients likely illustrate a rare autosomal dominant pre-Descemet crystalline keratopathy that has been reported only once previously.

  9. T2 relaxometry of brain in myotonic dystrophy

    International Nuclear Information System (INIS)

    Di Costanzo, A.; Bonavita, V.; Tedeschi, G.; Di Salle, F.; Santoro, L.

    2001-01-01

    We investigated the nature and extent of brain involvement in myotonic dystrophy (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was performed at 0.5 T, and T2 values were calculated from signal intensity in two echoes. Regions of interest included: frontal, parietal, temporal, occipital and callosal (rostral and splenial) normal-appearing white matter; frontal, occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus pallidus and thalamus. All white-matter and occipital and right frontal cortex regions showed a significantly longer T2 in the patients. Multiple regression analysis, including grey- and white-matter T2 as dependent variables, plus age at onset and at imaging, disease duration, muscular disability, brain atrophy and CTG trinucleotide repeats as independent variables, revealed that only white-matter T2 elongation and disease duration correlated positively. White-matter involvement in DM is more extensive than previously reported by MRI and neuropathological studies and seems to be progressive in the course of disease. (orig.)

  10. Recent Advancements in Gene Therapy for Hereditary Retinal Dystrophies

    Directory of Open Access Journals (Sweden)

    Ayşe Öner

    2017-12-01

    Full Text Available Hereditary retinal dystrophies (HRDs are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision, and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles, with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family, highlighting further levels of complexity. The known disease genes encode proteins involved in retinal cellular structures, phototransduction, the visual cycle, and photoreceptor structure or gene regulation. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been proposed as potentially efficacious therapies. Because of its favorable anatomical and immunological characteristics, the eye has been at the forefront of translational gene therapy. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Dozens of promising proofs of concept have been obtained in animal models of HRDs and some of them have been relayed to the clinic. The results from the first clinical trials for a congenital form of blindness have generated great interest and have demonstrated the safety and efficacy of intraocular administrations of viral vectors in humans. This review summarizes the clinical development of retinal gene therapy.

  11. Sleep disturbances in myotonic dystrophy type 2.

    Science.gov (United States)

    Shepard, Paul; Lam, Erek M; St Louis, Erik K; Dominik, Jacob

    2012-01-01

    Sleep disorders in myotonic dystrophy type 1 (DM1) are common and include sleep-disordered breathing, hypersomnia, and fatigue. Little is known regarding the occurrence of sleep disturbance in myotonic dystrophy type 2 (DM2). We hypothesized that DM2 patients may frequently harbor sleep disorders. We reviewed medical records of all genetically confirmed cases of DM2 seen at our sleep center between 1997 and 2010 for demographic, laboratory, overnight oximetry, and polysomnography (PSG) data. Eight patients (5 women, 3 men) with DM2 were identified. Excessive daytime sleepiness was seen in 6 patients (75%), insomnia in 5 (62.5%), and excessive fatigue in 4 (50%). Obstructive sleep apnea was diagnosed in 3 of 5 patients (60%) studied with PSG. Respiratory muscle weakness was present in all 6 patients (100%) who received pulmonary function testing. Four of 8 (50%) met criteria for diagnosis of restless legs syndrome. The clinical spectrum of DM2 may include a wide range of sleep disturbances. Although respiratory muscle weakness was frequent, sustained sleep-related hypoxia suggestive of hypoventilation was not seen in our patients. Further prospective studies are needed to examine the frequency and scope of sleep disturbances in DM2. Copyright © 2012 S. Karger AG, Basel.

  12. Muscle MRI findings in facioscapulohumeral muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Gerevini, Simonetta; Caliendo, Giandomenico; Falini, Andrea [IRCCS San Raffaele Scientific Institute, Neuroradiology Unit, Head and Neck Department, Milan (Italy); Scarlato, Marina; Previtali, Stefano Carlo [IRCCS San Raffaele Scientific Institute, Department of Neurology, INSPE and Division of Neuroscience, Milan (Italy); Maggi, Lorenzo; Pasanisi, Barbara; Morandi, Lucia [Fondazione IRCCS Istituto Neurologico ' ' Carlo Besta' ' , Neuromuscular Diseases and Neuroimmunology Unit, Milan (Italy); Cava, Mariangela [IRCCS San Raffaele Scientific Institute, Department of Radiology and Center for Experimental Imaging, Milan (Italy)

    2016-03-15

    Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations. Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD). In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients. In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease. (orig.)

  13. Myotonic Dystrophy Type 1 Management and Therapeutics.

    Science.gov (United States)

    Smith, Cheryl A; Gutmann, Laurie

    2016-12-01

    Myotonic dystrophy (DM1) is the most common form of adult muscular dystrophy. It is a multisystem disorder with a complex pathophysiology. Although inheritance is autosomal dominant, disease variability is attributed to anticipation, a maternal expansion bias, variable penetrance, somatic mosaicism, and a multitude of aberrant pre-mRNA splicing events. Patient presentations range from asymptomatic or mild late onset adult to severe congenital forms. Multiple organ systems may be affected. Patients may experience early cataracts, myotonia, muscle weakness/atrophy, fatigue, excessive daytime sleepiness, central/obstructive apnea, respiratory failure, cardiac arrhythmia, insulin resistance, dysphagia, GI dysmotility, cognitive impairment, Cluster C personality traits, and/or mood disorders. At present, there is no curative or disease-modifying treatment, although clinical treatment trials have become more promising. Management focuses on genetic counseling, preserving function and independence, preventing cardiopulmonary complications, and symptomatic treatment (e.g., pain, myotonia, hypersomnolence, etc.). Currently, there is an increasing international consensus on monitoring and treatment options for these patients which necessitates a multidisciplinary team to provide comprehensive, coordinated clinical care.

  14. Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping.

    Science.gov (United States)

    Vulin, Adeline; Barthélémy, Inès; Goyenvalle, Aurélie; Thibaud, Jean-Laurent; Beley, Cyriaque; Griffith, Graziella; Benchaouir, Rachid; le Hir, Maëva; Unterfinger, Yves; Lorain, Stéphanie; Dreyfus, Patrick; Voit, Thomas; Carlier, Pierre; Blot, Stéphane; Garcia, Luis

    2012-11-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder resulting from lesions of the gene encoding dystrophin. These usually consist of large genomic deletions, the extents of which are not correlated with the severity of the phenotype. Out-of-frame deletions give rise to dystrophin deficiency and severe DMD phenotypes, while internal deletions that produce in-frame mRNAs encoding truncated proteins can lead to a milder myopathy known as Becker muscular dystrophy (BMD). Widespread restoration of dystrophin expression via adeno-associated virus (AAV)-mediated exon skipping has been successfully demonstrated in the mdx mouse model and in cardiac muscle after percutaneous transendocardial delivery in the golden retriever muscular dystrophy dog (GRMD) model. Here, a set of optimized U7snRNAs carrying antisense sequences designed to rescue dystrophin were delivered into GRMD skeletal muscles by AAV1 gene transfer using intramuscular injection or forelimb perfusion. We show sustained correction of the dystrophic phenotype in extended muscle areas and partial recovery of muscle strength. Muscle architecture was improved and fibers displayed the hallmarks of mature and functional units. A 5-year follow-up ruled out immune rejection drawbacks but showed a progressive decline in the number of corrected muscle fibers, likely due to the persistence of a mild dystrophic process such as occurs in BMD phenotypes. Although AAV-mediated exon skipping was shown safe and efficient to rescue a truncated dystrophin, it appears that recurrent treatments would be required to maintain therapeutic benefit ahead of the progression of the disease.

  15. Sildenafil reduces respiratory muscle weakness and fibrosis in the mdx mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Percival, Justin M; Whitehead, Nicholas P; Adams, Marvin E; Adamo, Candace M; Beavo, Joseph A; Froehner, Stanley C

    2012-09-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy caused by mutations in the dystrophin gene. Loss of dystrophin initiates a progressive decline in skeletal muscle integrity and contractile capacity which weakens respiratory muscles including the diaphragm, culminating in respiratory failure, the leading cause of morbidity and mortality in DMD patients. At present, corticosteroid treatment is the primary pharmacological intervention in DMD, but has limited efficacy and adverse side effects. Thus, there is an urgent need for new safe, cost-effective, and rapidly implementable treatments that slow disease progression. One promising new approach is the amplification of nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signalling pathways with phosphodiesterase 5 (PDE5) inhibitors. PDE5 inhibitors serve to amplify NO signalling that is attenuated in many neuromuscular diseases including DMD. We report here that a 14-week treatment of the mdx mouse model of DMD with the PDE5 inhibitor sildenafil (Viagra(®), Revatio(®)) significantly reduced mdx diaphragm muscle weakness without impacting fatigue resistance. In addition to enhancing respiratory muscle contractility, sildenafil also promoted normal extracellular matrix organization. PDE5 inhibition slowed the establishment of mdx diaphragm fibrosis and reduced matrix metalloproteinase-13 (MMP-13) expression. Sildenafil also normalized the expression of the pro-fibrotic (and pro-inflammatory) cytokine tumour necrosis factor α (TNFα). Sildenafil-treated mdx diaphragms accumulated significantly less Evans Blue tracer dye than untreated controls, which is also indicative of improved diaphragm muscle health. We conclude that sildenafil-mediated PDE5 inhibition significantly reduces diaphragm respiratory muscle dysfunction and pathology in the mdx mouse model of Duchenne muscular dystrophy. This study provides new insights into the therapeutic utility of targeting defects in NO

  16. Evaluation of myocardial abnormalities in patients with collagen diseases by thallium-201 myocardial scintigram

    Energy Technology Data Exchange (ETDEWEB)

    Yamano, Shigeru (Nara Medical Univ., Kashihara (Japan))

    1992-08-01

    This study was performed to evaluate myocardial lesions in patients with collagen diseases by rest and exercise thallium-201 myocardial scintigraphies. A total of 76 patients without ischemic ECG changes, consisting of 27 cases of systemic lupus erythematosus (SLE), 17 cases of polymyositis or dermatomyositis (PM[center dot]DM), 11 cases of progressive systemic sclerosis (PSS), and 21 cases of Sjoegren's syndrome (SjS), were enrolled in this study. Reversible exercise-induced defects suggesting myocardial ischemia were noted in 12 cases of SLE, 5 cases of PM[center dot]DM, 3 cases of PSS, and 3 cases of SjS. Of the 23 patients who had exercise-induced defects, 9 patients showed normal coronary angiograms by cardiac catheterization. Fixed hypoperfusion areas were observed in 5 cases of SLE, 6 cases of PM[center dot]DM, 4 cases of PSS and 3 cases of SjS. Rest thallium-201 myocardial scintigraphy disclosed hypoperfusion areas, which were not induced by exercise, in 1 case of SLE, 4 cases of PM[center dot]DM, 1 case of PSS and 5 cases of SjS. Endomyocardial biopsy was performed on 20 patients. Myocardial lesions in PM[center dot]DM and PSS were more severe and wide spread than in SLE. Ejection fraction and fractional shortening evaluated by echocardiography had no significant differences between each disease group and the healthy control group. These findings suggest that patients with collagen diseases show the presence of abnormalities of coronary circulation at the level of the intramyocardial vasculature in the stage before impairment of cardiac function, myocardial fibrosis and functional abnormalities of the cell membrane level that were not dependent on myocardial ischemia. (author).

  17. The golden retriever model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Kornegay, Joe N

    2017-05-19

    Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the DMD gene and loss of the protein dystrophin. The absence of dystrophin leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade due to either respiratory failure or cardiomyopathy. Despite extensive attempts to develop definitive therapies for DMD, the standard of care remains prednisone, which has only palliative benefits. Animal models, mainly the mdx mouse and golden retriever muscular dystrophy (GRMD) dog, have played a key role in studies of DMD pathogenesis and treatment development. Because the GRMD clinical syndrome is more severe than in mice, better aligning with the progressive course of DMD, canine studies may translate better to humans. The original founder dog for all GRMD colonies worldwide was identified in the early 1980s before the discovery of the DMD gene and dystrophin. Accordingly, analogies to DMD were initially drawn based on similar clinical features, ranging from the X-linked pattern of inheritance to overlapping histopathologic lesions. Confirmation of genetic homology between DMD and GRMD came with identification of the underlying GRMD mutation, a single nucleotide change that leads to exon skipping and an out-of-frame DMD transcript. GRMD colonies have subsequently been established to conduct pathogenetic and preclinical treatment studies. Simultaneous with the onset of GRMD treatment trials, phenotypic biomarkers were developed, allowing definitive characterization of treatment effect. Importantly, GRMD studies have not always substantiated findings from mdx mice and have sometimes identified serious treatment side effects. While the GRMD model may be more clinically relevant than the mdx mouse, usage has been limited by practical considerations related to expense and the number of dogs available. This further complicates ongoing broader concerns about

  18. Vascular-targeted therapies for Duchenne muscular dystrophy

    Science.gov (United States)

    2013-01-01

    Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy and an X-linked recessive, progressive muscle wasting disease caused by the absence of a functional dystrophin protein. Dystrophin has a structural role as a cytoskeletal stabilization protein and protects cells against contraction-induced damage. Dystrophin also serves a signaling role through mechanotransduction of forces and localization of neuronal nitric oxide synthase (nNOS), which produces nitric oxide (NO) to facilitate vasorelaxation. In DMD, the signaling defects produce inadequate tissue perfusion caused by functional ischemia due to a diminished ability to respond to shear stress induced endothelium-dependent dilation. Additionally, the structural defects seen in DMD render myocytes with an increased susceptibility to mechanical stress. The combination of both defects is necessary to generate myocyte damage, which induces successive rounds of myofiber degeneration and regeneration, loss of calcium homeostasis, chronic inflammatory response, fibrosis, and myonecrosis. In individuals with DMD, these processes inevitably cause loss of ambulation shortly after the first decade and an abbreviated life with death in the third or fourth decade due to cardio-respiratory anomalies. There is no known cure for DMD, and although the culpable gene has been identified for more than twenty years, research on treatments has produced few clinically relevant results. Several recent studies on novel DMD therapeutics are vascular targeted and focused on attenuating the inherent functional ischemia. One approach improves vasorelaxation capacity through pharmaceutical inhibition of either phosphodiesterase 5 (PDE5) or angiotensin-converting enzyme (ACE). Another approach increases the density of the underlying vascular network by inducing angiogenesis, and this has been accomplished through either direct delivery of vascular endothelial growth factor (VEGF) or by downregulating the VEGF decoy

  19. Serum creatinine level: a supplemental index to distinguish Duchenne muscular dystrophy from Becker muscular dystrophy.

    Science.gov (United States)

    Zhang, Huili; Zhu, Yuling; Sun, Yiming; Liang, Yingyin; Li, Yaqin; Zhang, Yu; Deng, Langhui; Wen, Xingxuan; Zhang, Cheng

    2015-01-01

    To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn) level reflects disease severity. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. Serum Crn level had a strong inverse correlation with Vignos score by simple correlation (r = -0.793) and partial correlation analysis after adjustment for age, height, and weight (r = -0.791; both P Becker muscular dystrophy (BMD) patients than Duchenne muscular dystrophy (DMD) patients at ages 4, 5, 7, and 9 yr (all P < 0.0125). After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients (β = 7.140,  t = 6.277,  P < 0.01). Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice.

  20. Guidelines for the Perianesthesia Care of the Duchenne Muscular Dystrophy/Becker Muscular Dystrophy Patient.

    Science.gov (United States)

    Alliod, Barbara A; Ash, Rebecca A

    2016-12-01

    More patients suffering with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are presenting to perianesthesia settings for emergent and nonemergent treatment and care. A group of collaborative health care providers at Rush University Medical Center in Chicago developed a multidisciplinary DMD/BMD Task Force to study this disorder and create a set of guidelines to aid those engaging in the planning, execution of care, and recovery of this unique population in the perianesthesia setting. Attention to detail, well-executed preplanning, meticulous awareness of the patient, and prearranged implementation and intervention has proven to offset potential problems and complications and is the key to a successful perianesthesia period. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  1. Evaluation of myocardial abnormalities in collagen diseases by thallium-201 myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yamano, Shigeru; Kagoshima, Tadashi; Sugihara, Kiyotaka (Nara Medical Univ., Kashihara (Japan)) (and others)

    1993-12-01

    This study was performed to evaluate myocardial abnormalities in patients with collagen diseases by exercise and rest thallium-201 myocardial scintigrams. A total of 65 patients without ischemic ECG changes, consisting of 18 with systemic lupus erythematosus (SLE), 18 with polymyositis (PM), 8 with progressive systemic sclerosis (PSS), and 21 with Sjoegren's syndrome (SjS), was enrolled in this study. Reversible exercise-induced defects scintigraphically suggesting myocardial ischemia were noted in 8 cases of SLE, 4 cases of PM, 4 cases of PSS, and 3 cases of SjS. Nineteen patients had exercise-induced defects and underwent cardiac catheterization, 8 of whom had normal coronary angiograms. Fixed hypoperfusion areas were observed in one case of SLE, 6 cases of PM and 3 cases of SjS. Rest thallium-201 myocardial scintigram disclosed hypoperfusion areas which were not induced by exercise in 2 cases of SLE, 3 cases of PM, one case of PSS and 5 cases of SjS. Echocardiogram showed no significant differences in ejection fraction and % fractional shortening between the disease groups and healthy control group. These findings suggest that patients with collagen diseases have abnormalities of coronary circulation at the level of the intramural vasculature before cardiac function impairment, myocardial fibrosis and functional abnormalities at the cell membrane. (author).

  2. A case report: Becker muscular dystrophy presenting with epilepsy and dysgnosia induced by duplication mutation of Dystrophin gene.

    Science.gov (United States)

    Miao, Jing; Feng, Jia-Chun; Zhu, Dan; Yu, Xue-Fan

    2016-12-12

    Becker muscular dystrophy (BMD), a genetic disorder of X-linked recessive inheritance, typically presents with gradually progressive muscle weakness. The condition is caused by mutations of Dystrophin gene located at Xp21.2. Epilepsy is an infrequent manifestation of BMD, while cases of BMD with dysgnosia are extremely rare. We describe a 9-year-old boy with BMD, who presented with epilepsy and dysgnosia. Serum creatine kinase level was markedly elevated (3665 U/L). Wechsler intelligence tests showed a low intelligence quotient (IQ = 65). Electromyogram showed slight myogenic changes and skeletal muscle biopsy revealed muscular dystrophy. Immunohistochemical staining showed partial positivity of sarcolemma for dystrophin-N. Multiplex ligation-dependent probe amplification revealed a duplication mutation in exons 37-44 in the Dystrophin gene. The present case report helps to better understand the clinical and genetic features of BMD.

  3. AMP-activated protein kinase at the nexus of therapeutic skeletal muscle plasticity in Duchenne muscular dystrophy.

    Science.gov (United States)

    Ljubicic, Vladimir; Jasmin, Bernard J

    2013-10-01

    Recent studies have highlighted the potential of adenosine monophosphate-activated protein kinase (AMPK) to act as a central therapeutic target in Duchenne muscular dystrophy (DMD). Here, we review the role of AMPK as an important integrator of cell signaling pathways that mediate phenotypic plasticity within the context of dystrophic skeletal muscle. Pharmacological AMPK activation remodels skeletal muscle towards a slower, more oxidative phenotype, which is more pathologically resistant to the lack of dystrophin. Moreover, recent studies suggest that AMPK-activated autophagy may be beneficial for myofiber structure and function in mice with muscular dystrophy. Thus, AMPK may represent an ideal target for intervention because clinically approved pharmacological agonists exist, and because benefits can be derived via two independent yet, complementary biological pathways. The availability of several AMPK activators could therefore lead to the rapid development and implementation of novel and highly effective therapeutics aimed at altering the relentless progression of DMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Dystrophin analysis in carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    Hoogerwaard, Edo M.; Ginjaar, Ieke B.; Bakker, Egbert; de Visser, Marianne

    2005-01-01

    Associations between clinical phenotype (muscle weakness, dilated cardiomyopathy) and dystrophin abnormalities in muscle tissue among definite carriers of Duchenne (DMD) and Becker muscular dystrophy (BMD) were investigated. No associations between dystrophin abnormalities and clinical variables in

  5. A new chart for weight control in Duchenne muscular dystrophy.

    OpenAIRE

    Griffiths, R D; Edwards, R H

    1988-01-01

    Weight control is desirable in the muscle wasting conditions. A new chart is presented to allow the prediction of an ideal weight, free of excess fat, specifically for boys with Duchenne muscular dystrophy.

  6. Nonmuscular involvement in merosin-negative congenital muscular dystrophy.

    NARCIS (Netherlands)

    Gilhuis, H.J.; Donkelaar, H.J. ten; Tanke, R.B.; Vingerhoets, D.M.; Zwarts, M.J.; Verrips, A.; Gabreëls, F.J.M.

    2002-01-01

    The spectrum of nonmuscular involvement in six children with merosin-negative congenital muscular dystrophy is described. In all children, biochemical, neuroradiologic, cardiac, and neurophysiologic studies were performed. Cerebral structures that were myelinated at gestation, including internal

  7. How Physicians Support Mothers of Children with Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Fujino, Haruo; Saito, Toshio; Matsumura, Tsuyoshi; Shibata, Saki; Iwata, Yuko; Fujimura, Harutoshi; Shinno, Susumu; Imura, Osamu

    2015-09-01

    Communicating about Duchenne muscular dystrophy and its prognosis can be difficult for affected children and their family. We focused on how physicians provide support to the mothers of children with Duchenne muscular dystrophy who have difficulty communicating about the condition with their child. The eligible participants were certified child neurologists of the Japanese Society of Child Neurology. Participants responded to questionnaires consisting of free descriptions of a vignette of a child with Duchenne muscular dystrophy and a mother. We analyzed 263 responses of the participants. We found 4 themes on advising mothers, involving encouraging communication, family autonomy, supporting family, and considering the child's concerns. These results provide a better understanding of the communication between physicians and family members who need help sharing information with a child with Duchenne muscular dystrophy. These findings will assist clinical practitioners in supporting families and the affected children throughout the course of their illness. © The Author(s) 2015.

  8. Clinical and molecular genetic analysis of best vitelliform macular dystrophy.

    NARCIS (Netherlands)

    Boon, C.J.F.; Theelen, T.; Hoefsloot, L.H.; Schooneveld, M.J. van; Keunen, J.E.E.; Cremers, F.P.M.; Klevering, B.J.; Hoyng, C.B.

    2009-01-01

    PURPOSE: To describe the phenotype of Best vitelliform macular dystrophy (BVMD) and to evaluate genotype-phenotype and histopathologic correlations. METHODS: Retrospective analysis of patients with BVMD who underwent an extensive ophthalmic examination, including best-corrected Snellen visual

  9. CLINICAL AND MOLECULAR GENETIC ANALYSIS OF BEST VITELLIFORM MACULAR DYSTROPHY

    NARCIS (Netherlands)

    Boon, Camiel J. F.; Theelen, Thomas; Hoefsloot, Elisabeth H.; van Schooneveld, Mary J.; Keunen, Jan E. E.; Cremers, Frans P. M.; Klevering, B. Jeroen; Hoyng, Carel B.

    2009-01-01

    Purpose: To describe the phenotype of Best vitelliform macular dystrophy (BVMD) and to evaluate genotype-phenotype and histopathologic correlations. Methods: Retrospective analysis of patients with BVMD who underwent an extensive ophthalmic examination, including best-corrected Snellen visual

  10. Predictive factors for masticatory performance in Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Bruggen, H.W. van; Engel-Hoek, L. van den; Steenks, M.H.; Bronkhorst, E.M.; Creugers, N.H.; Groot, I.J.M. de; Kalaykova, S.

    2014-01-01

    Patients with Duchenne muscular dystrophy (DMD) report masticatory and swallowing problems. Such problems may cause complications such as choking, and feeling of food sticking in the throat. We investigated whether masticatory performance in DMD is objectively impaired, and explored predictive

  11. Strength training and albuterol in facioscapulohumeral muscular dystrophy

    NARCIS (Netherlands)

    van der Kooi, EL; Vogels, OJM; van Asseldonk, RJGP; Lindeman, E; Hendriks, JCM; Wohlgemuth, M; van der Maarel, SM; Padberg, GW

    2004-01-01

    Background: In animals and healthy volunteers beta2-adrenergic agonists increase muscle strength and mass, in particular when combined with strength training. In patients with facioscapulohumeral muscular dystrophy (FSHD) albuterol may exert anabolic effects. The authors evaluated the effect of

  12. Macular pattern dystrophy and homonymous hemianopia in MELAS syndrome.

    Science.gov (United States)

    Kamal-Salah, Radua; Baquero-Aranda, Isabel; Grana-Pérez, María Del Mar; García-Campos, Jose Manuel

    2015-03-12

    We report an unusual association of a pattern dystrophy of the retinal pigment epithelium and homonymous hemianopia in a woman diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome. 2015 BMJ Publishing Group Ltd.

  13. Cardiac considerations in the operative management of the patient with Duchenne or Becker muscular dystrophy.

    Science.gov (United States)

    Cripe, Linda H; Tobias, Joseph D

    2013-09-01

    Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) is a progressive multisystem neuromuscular disorder. In addition to the skeletal muscle, the myocardium in the DMD/BMD patient is dystrophin deficient which results in a progressive cardiomyopathy. The myopathic myocardium poses significant risk of increased morbidity and mortality at the time of major surgical procedures. Careful attention must be given to the DMD/BMD patient during the intraoperative and postoperative period. Anesthesia selection is critical and anesthetics should be avoided which have been shown to be harmful in this patient population. Preanesthesia assessment should include cardiac consultation and detailed preoperative evaluation. Intraoperative management needs to insure that the weakened myocardium is not compromised by physiologic changes such as hypotension or major fluid shifts. Finally, attention to the cardiac status of the patient must continue into the postoperative period. The surgical care of the DMD/BMD patient requires a multispecialty approach to insure operative success. © 2013 John Wiley & Sons Ltd.

  14. A current approach to heart failure in Duchenne muscular dystrophy.

    Science.gov (United States)

    D'Amario, Domenico; Amodeo, Antonio; Adorisio, Rachele; Tiziano, Francesco Danilo; Leone, Antonio Maria; Perri, Gianluigi; Bruno, Piergiorgio; Massetti, Massimo; Ferlini, Alessandra; Pane, Marika; Niccoli, Giampaolo; Porto, Italo; D'Angelo, Gianluca A; Borovac, Josip Anđelo; Mercuri, Eugenio; Crea, Filippo

    2017-11-01

    Duchenne muscular dystrophy (DMD) is a genetic, progressive neuromuscular condition that is marked by the long-term muscle deterioration with significant implications of pulmonary and cardiac dysfunction. As such, end-stage heart failure (HF) in DMD is increasingly becoming the main cause of death in this population. The early detection of cardiomyopathy is often challenging, due to a long subclinical phase of ventricular dysfunction and difficulties in assessment of cardiovascular symptomatology in these patients who usually loose ambulation during the early adolescence. However, an early diagnosis of cardiovascular disease in patients with DMD is decisive since it allows a timely initiation of cardioprotective therapies that can mitigate HF symptoms and delay detrimental heart muscle remodelling. Echocardiography and ECG are standardly used for screening and detection of cardiovascular abnormalities in these patients, although these tools are not always adequate to detect an early, clinically asymptomatic phases of disease progression. In this regard, cardiovascular magnetic resonance (CMR) with late gadolinium enhancement is emerging as a promising method for the detection of early cardiac involvement in patients with DMD. The early detection of cardiac dysfunction allows the therapeutic institution of various classes of drugs such as corticosteroids, beta-blockers, ACE inhibitors, antimineralocorticoid diuretics and novel pharmacological and surgical solutions in the multimodal and multidisciplinary care for this group of patients. This review will focus on these challenges and available options for HF in patients with DMD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. [Central aleolar choroidal dystrophy in sibilings coexisting with alopecia].

    Science.gov (United States)

    Brydak-Godowska, Joanna; Dróbecka-Brydak, Ewa; Paćkowska, Maria; Kecik, Dariusz

    2007-01-01

    Central areolar choroidal dystrophy is localized in macular region and is characterized by atrophy of pigment epithelium, photoreceptors and choriocapillaris. This paper presents the history of two sibilings at the age of 23 and 30, with central aleolar choroidal dystrophy coexisting with alopecia. The results of erg, eog and fluorescein angiography are presented. The results of therapy for glaucoma associated with the Sturge-Weber syndrome are often disappointing.

  16. Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

    Science.gov (United States)

    Finder, Jonathan; Mayer, Oscar Henry; Sheehan, Daniel; Sawnani, Hemant; Abresch, R Ted; Benditt, Joshua; Birnkrant, David J; Duong, Tina; Henricson, Erik; Kinnett, Kathi; McDonald, Craig M; Connolly, Anne M

    2017-08-15

    Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

  17. Prevalence and correlates of apathy in myotonic dystrophy type 1

    OpenAIRE

    Gallais, Benjamin; Montreuil, Mich?le; Gargiulo, Marcela; Eymard, Bruno; Gagnon, Cynthia; Laberge, Luc

    2015-01-01

    Background Apathy in DM1 has long been acknowledged in clinical practice. However, a major drawback is that the concept has been only sparsely explored in previous specific studies. This study aimed to determine the prevalence of apathy in myotonic dystrophy (DM1), to compare it with facioscapulohumeral dystrophy (FSHD) patients and normal healthy controls, and explore its relationship to psychopathological features and cognitive function. Methods Levels of apathy in 38 DM1 patients with adul...

  18. Concurrence of myotonic dystrophy and epilepsy: a case report

    OpenAIRE

    Worku, Dawit Kibru

    2014-01-01

    Introduction Myotonic dystrophy is a clinically and genetically heterogeneous multisystem disorder with a prevalence of 1 in 8000 in the general population. Case presentation A 25-year-old Ethiopian man presented with symptoms of myotonia, muscle wasting, gait problems, frontal baldness, and family history characterizing the hereditary disorder myotonic dystrophy. He had been on treatment for idiopathic generalized epilepsy for over 15 years. A needle electromyography showed insertional class...

  19. Profiles of Steroid Hormones in Canine X-Linked Muscular Dystrophy via Stable Isotope Dilution LC-MS/MS.

    Directory of Open Access Journals (Sweden)

    Helio A Martins-Júnior

    Full Text Available Golden retriever muscular dystrophy (GRMD provides the best animal model for characterizing the disease progress of the human disorder, Duchenne muscular dystrophy (DMD. The purpose of this study was to determine steroid hormone concentration profiles in healthy golden retriever dogs (control group - CtGR versus GRMD-gene carrier (CaGR and affected female dogs (AfCR. Therefore, a sensitive and specific analytical method was developed and validated to determine the estradiol, progesterone, cortisol, and testosterone levels in the canine serum by isotope dilution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS. To more accurately understand the dynamic nature of the serum steroid profile, the fluctuating levels of these four steroid hormones over the estrous cycle were compared across the three experimental groups using a multivariate statistical analysis. The concentration profiles of estradiol, cortisol, progesterone, and testosterone revealed a characteristic pattern for each studied group at each specific estrous phase. Additionally, several important changes in the serum concentrations of cortisol and estradiol in the CaGR and AfCR groups seem to be correlated with the status and progression of the muscular dystrophy. A comprehensive and quantitative monitoring of steroid profiles throughout the estrous cycle of normal and GRMD dogs were achieved. Significant differences in these profiles were observed between GRMD and healthy animals, most notably for estradiol. These findings contribute to a better understanding of both dog reproduction and the muscular dystrophy pathology. Our data open new venues for hormonal behavior studies in dystrophinopathies and that may affect the quality of life of DMD patients.

  20. Correlation of Utrophin Levels with the Dystrophin Protein Complex and Muscle Fibre Regeneration in Duchenne and Becker Muscular Dystrophy Muscle Biopsies.

    Science.gov (United States)

    Janghra, Narinder; Morgan, Jennifer E; Sewry, Caroline A; Wilson, Francis X; Davies, Kay E; Muntoni, Francesco; Tinsley, Jonathon

    2016-01-01

    Duchenne muscular dystrophy is a severe and currently incurable progressive neuromuscular condition, caused by mutations in the DMD gene that result in the inability to produce dystrophin. Lack of dystrophin leads to loss of muscle fibres and a reduction in muscle mass and function. There is evidence from dystrophin-deficient mouse models that increasing levels of utrophin at the muscle fibre sarcolemma by genetic or pharmacological means significantly reduces the muscular dystrophy pathology. In order to determine the efficacy of utrophin modulators in clinical trials, it is necessary to accurately measure utrophin levels and other biomarkers on a fibre by fibre basis within a biopsy section. Our aim was to develop robust and reproducible staining and imaging protocols to quantify sarcolemmal utrophin levels, sarcolemmal dystrophin complex members and numbers of regenerating fibres within a biopsy section. We quantified sarcolemmal utrophin in mature and regenerating fibres and the percentage of regenerating muscle fibres, in muscle biopsies from Duchenne, the milder Becker muscular dystrophy and controls. Fluorescent immunostaining followed by image analysis was performed to quantify utrophin intensity and β-dystrogylcan and ɣ -sarcoglycan intensity at the sarcolemma. Antibodies to fetal and developmental myosins were used to identify regenerating muscle fibres allowing the accurate calculation of percentage regeneration fibres in the biopsy. Our results indicate that muscle biopsies from Becker muscular dystrophy patients have fewer numbers of regenerating fibres and reduced utrophin intensity compared to muscle biopsies from Duchenne muscular dystrophy patients. Of particular interest, we show for the first time that the percentage of regenerating muscle fibres within the muscle biopsy correlate with the clinical severity of Becker and Duchenne muscular dystrophy patients from whom the biopsy was taken. The ongoing development of these tools to quantify

  1. Correlation of Utrophin Levels with the Dystrophin Protein Complex and Muscle Fibre Regeneration in Duchenne and Becker Muscular Dystrophy Muscle Biopsies.

    Directory of Open Access Journals (Sweden)

    Narinder Janghra

    Full Text Available Duchenne muscular dystrophy is a severe and currently incurable progressive neuromuscular condition, caused by mutations in the DMD gene that result in the inability to produce dystrophin. Lack of dystrophin leads to loss of muscle fibres and a reduction in muscle mass and function. There is evidence from dystrophin-deficient mouse models that increasing levels of utrophin at the muscle fibre sarcolemma by genetic or pharmacological means significantly reduces the muscular dystrophy pathology. In order to determine the efficacy of utrophin modulators in clinical trials, it is necessary to accurately measure utrophin levels and other biomarkers on a fibre by fibre basis within a biopsy section. Our aim was to develop robust and reproducible staining and imaging protocols to quantify sarcolemmal utrophin levels, sarcolemmal dystrophin complex members and numbers of regenerating fibres within a biopsy section. We quantified sarcolemmal utrophin in mature and regenerating fibres and the percentage of regenerating muscle fibres, in muscle biopsies from Duchenne, the milder Becker muscular dystrophy and controls. Fluorescent immunostaining followed by image analysis was performed to quantify utrophin intensity and β-dystrogylcan and ɣ -sarcoglycan intensity at the sarcolemma. Antibodies to fetal and developmental myosins were used to identify regenerating muscle fibres allowing the accurate calculation of percentage regeneration fibres in the biopsy. Our results indicate that muscle biopsies from Becker muscular dystrophy patients have fewer numbers of regenerating fibres and reduced utrophin intensity compared to muscle biopsies from Duchenne muscular dystrophy patients. Of particular interest, we show for the first time that the percentage of regenerating muscle fibres within the muscle biopsy correlate with the clinical severity of Becker and Duchenne muscular dystrophy patients from whom the biopsy was taken. The ongoing development of these

  2. Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study.

    Directory of Open Access Journals (Sweden)

    Patricia Hafner

    Full Text Available Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d and metformin (2 x 250 mg/d for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients.ClinicalTrials.gov NCT02516085.

  3. Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study.

    Science.gov (United States)

    Hafner, Patricia; Bonati, Ulrike; Erne, Beat; Schmid, Maurice; Rubino, Daniela; Pohlman, Urs; Peters, Thomas; Rutz, Erich; Frank, Stephan; Neuhaus, Cornelia; Deuster, Stefanie; Gloor, Monika; Bieri, Oliver; Fischmann, Arne; Sinnreich, Michael; Gueven, Nuri; Fischer, Dirk

    2016-01-01

    Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients. ClinicalTrials.gov NCT02516085.

  4. Myocardial scintigraphy with thallium-201

    Energy Technology Data Exchange (ETDEWEB)

    Lichte, H [Zentralkrankenhaus Gauting (Germany, F.R.). Nuklearmedizinische Abt.

    1977-04-01

    Myocardial scintigraphy with /sup 201/thallium is a non-invasive method for detection of myocardial infarction and coronary heart disease. Redistribution-analysis as a sequential-scintigraphy of an exercise-scan permits to distinguish between myocardial scars and coronary vessel disease.

  5. Comparison of left ventricular function assessment between echocardiography and MRI in Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Buddhe, Sujatha; Lewin, Mark; Olson, Aaron; Soriano, Brian D. [University of Washington School of Medicine and Seattle Children' s Hospital, Division of Cardiology, Department of Pediatrics, Seattle, WA (United States); Ferguson, Mark [University of Washington School of Medicine and Seattle Children' s Hospital, Department of Radiology, Seattle, WA (United States)

    2016-09-15

    Cardiomyopathy in Duchenne muscular dystrophy (DMD) is associated with death in approximately 40% of patients. Echocardiography is routinely used to assess left ventricular (LV) function; however, it has limitations in these patients. We compared echocardiographic measures of cardiac function assessment to cardiac MRI. We included children and young adults with DMD who had MRI performed between January 2010 and July 2015. We measured echocardiographic and MRI parameters of function assessment, including strain. Presence of late gadolinium enhancement (LGE) was assessed by MRI. Subjects were divided into two groups based on MRI left ventricular ejection fraction (LVEF): group I, LVEF ≥55% and group II, LVEF <55%. We included 41 studies in 33 subjects, with 25 in group I and 16 in group II. Mean age of subjects was 13.6 ± 2.8 years and mean duration between echocardiogram and MRI was 7.6 ± 4.1 months. Only 8 of 16 (50%) patients in group II had diminished function on echocardiogram. Echocardiographic images were suboptimal in 16 subjects (39%). Overall, echocardiographic parameters had weak correlation with MRI-derived ejection fraction percentage. MRI-derived myocardial strain assessment has better correlation with MRI ejection fraction as compared to echocardiography-derived strain parameters. Echocardiography-based ventricular functional assessment has weak correlation with MRI parameters in children and young adults with Duchenne muscular dystrophy. While this correlation improves in the subset of subjects with adequate echocardiographic image quality, it remains modest and potentially suboptimal for clinical management. Accordingly, we conclude that MRI should be performed routinely and early in children with DMD, not only for LGE imaging but also for functional assessment. (orig.)

  6. Comparison of left ventricular function assessment between echocardiography and MRI in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Buddhe, Sujatha; Lewin, Mark; Olson, Aaron; Soriano, Brian D.; Ferguson, Mark

    2016-01-01

    Cardiomyopathy in Duchenne muscular dystrophy (DMD) is associated with death in approximately 40% of patients. Echocardiography is routinely used to assess left ventricular (LV) function; however, it has limitations in these patients. We compared echocardiographic measures of cardiac function assessment to cardiac MRI. We included children and young adults with DMD who had MRI performed between January 2010 and July 2015. We measured echocardiographic and MRI parameters of function assessment, including strain. Presence of late gadolinium enhancement (LGE) was assessed by MRI. Subjects were divided into two groups based on MRI left ventricular ejection fraction (LVEF): group I, LVEF ≥55% and group II, LVEF <55%. We included 41 studies in 33 subjects, with 25 in group I and 16 in group II. Mean age of subjects was 13.6 ± 2.8 years and mean duration between echocardiogram and MRI was 7.6 ± 4.1 months. Only 8 of 16 (50%) patients in group II had diminished function on echocardiogram. Echocardiographic images were suboptimal in 16 subjects (39%). Overall, echocardiographic parameters had weak correlation with MRI-derived ejection fraction percentage. MRI-derived myocardial strain assessment has better correlation with MRI ejection fraction as compared to echocardiography-derived strain parameters. Echocardiography-based ventricular functional assessment has weak correlation with MRI parameters in children and young adults with Duchenne muscular dystrophy. While this correlation improves in the subset of subjects with adequate echocardiographic image quality, it remains modest and potentially suboptimal for clinical management. Accordingly, we conclude that MRI should be performed routinely and early in children with DMD, not only for LGE imaging but also for functional assessment. (orig.)

  7. Reflex sympathetic dystrophy syndrome: MR imaging study

    International Nuclear Information System (INIS)

    Masciocchi, C.; Fascetti, E.; Bonanni, G.; Calvisi, V.; Buoni, C.; Passariello, R.

    1987-01-01

    Reflex sympathetic dystrophy syndrome (RSDS) is characterized by pain, swelling, and limitation of motion. The etiology and pathophysiology mechanism have not yet been identified. We considered eight patients with clinical signs of RSDS, in five cases located at the knee joint and in three cases in the hip. In all cases conventional radiography and radionuclide bone scanning were performed before MR imaging. Conventional radiography was negative in three cases while scintigraphy demonstrated the lesion in all patients. MR imaging showed an area of low intensity signal on T1-weighted scans and an increased signal intensity on T2-weighted images. This area is located at the bone marrow and its regular and homogeneous. This specific finding on MR images is due to reflect edema by hyperemia of the bone marrow. The MR imaging diagnosis was confirmed on clinical and radiological follow-up. MR imaging can have a role in the differential diagnosis when other studies are nondiagnostic or nonspecific for RSDS

  8. Fibroblast cultures in duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Ionasescu, V.; Lara-Braud, C.; Zellweger, H.; Ionasescu, R.; Burmeister, L.

    1977-01-01

    Primary skin fibroblast cultures were grown from forearm pinch skin biopsies obtained from 24 patients with Duchenne muscular dystrophy (DMD) and ten normal controls matched for sex and age. The first subcultures were grown for 7 days and incubated with L-( 3 H)-proline for 24 hours. Intracellular collagen incoption was significantly decreased (2.2 X) and extracellular collagen incorporation significantly increased (1.8 X) in fibroblast cultures from patients with DMD by both collagenase assay and polyacrylamide gel electrophoresis. The synthesis of noncollagen proteins showed low values from the DMD fibroblast cultures. The alterations in synthesis and secretion of collagen and noncollagen proteins were characteristic only for the log phase of DMD fibroblasts. (author)

  9. The Myocardial Unfolded Protein Response during Ischemic Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Edward B. Thorp

    2012-01-01

    Full Text Available Heart failure is a progressive and disabling disease. The incidence of heart failure is also on the rise, particularly in the elderly of industrialized societies. This is in part due to an increased ageing population, whom initially benefits from improved, and life-extending cardiovascular therapy, yet ultimately succumb to myocardial failure. A major cause of heart failure is ischemia secondary to the sequence of events that is dyslipidemia, atherosclerosis, and myocardial infarction. In the case of heart failure postmyocardial infarction, ischemia can lead to myocardial cell death by both necrosis and apoptosis. The extent of myocyte death postinfarction is associated with adverse cardiac remodeling that can contribute to progressive heart chamber dilation, ventricular wall thinning, and the onset of loss of cardiac function. In cardiomyocytes, recent studies indicate that myocardial ischemic injury activates the unfolded protein stress response (UPR and this is associated with increased apoptosis. This paper focuses on the intersection of ischemia, the UPR, and cell death in cardiomyocytes. Targeting of the myocardial UPR may prove to be a viable target for the prevention of myocyte cell loss and the progression of heart failure due to ischemic injury.

  10. Myocardial myoglobin release after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, P S; Saltissi, S; Coltart, D J; Croft, D N [Saint Thomas' Hospital, London (UK)

    1980-03-01

    The magnitude and time course of myoglobin release from the myocardium following infarction was assessed by radioimmunoassay. The assay showed acceptable precision over a working range from 50 to 750 ng cm/sup -3/, provided careful control of the assay temperature was maintained. The use of this radioimmunoassay as an early diagnostic test for infarction and as a potential measure of the extent of necrosis is considered and comparison made with the release of CK-MB, the myocardial specific isoenzyme of creatine kinase. Of the twenty patients studied with myocardial infarction, all had elevated levels of serum myoglobin including those admitted within 3 hours of the onset of pain. In contrast, CK-MB was not detected in the serum within 5 hours of the onset of pain. Peak serum levels of myoglobin (mean 852 +- 365 ng cm/sup -3/) and CK-MB (mean 71 +- 25 mIU cm/sup -3/) were detected at 8-16 hours and 20-24 hours respectively after the onset of pain. A comparison of peak serum levels of myoglobin and CK-MB showed a good correlation (r = 0.84).

  11. Reversible myocardial ischaemia or irreversible myocardial fibrosis

    International Nuclear Information System (INIS)

    Mathey, D.; Hanrath, P.; Kupper, W.; Bleifeld, W.; Montz, R.; Knop, J.; Stritzke, P.; Kroeger, E.; Bleese, N.

    1978-01-01

    The results of biphasis 201 thallium ( 201 Tl) scanning were compared with those of coronary arteriography, left ventricular angiography and stress ECG in 56 patients with coronary artery disease and six with no evidence of heart disease. There were 104 201 Tl defects, 50 of them reversible. The defects were always located in the area supplied by a critically stenotic coronary artery. Correlation of regional wall motion with 201 Tl activity demonstrated that in all forms of abnormal wall motion there was either ischaemia or fibrosis. The resting LV angiogram thus does not make it possible to distinguish between myocardial ischaemia and fibrosis. Taking the LV angiogram as a standard, the rate of false-positive 201 Tl scintigrams was 5%, that of false-negative ones 23%. The biphasic 201 Tl scintigram was more sensitive than the stress ECG in detecting myocardial ischaemia. It furthermore made it possible to localize the ischaemic (or fibrotic) region within the LV and to estimate its size. (orig.) [de

  12. Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy.

    Science.gov (United States)

    Barnard, Alison M; Willcocks, Rebecca J; Finanger, Erika L; Daniels, Michael J; Triplett, William T; Rooney, William D; Lott, Donovan J; Forbes, Sean C; Wang, Dah-Jyuu; Senesac, Claudia R; Harrington, Ann T; Finkel, Richard S; Russman, Barry S; Byrne, Barry J; Tennekoon, Gihan I; Walter, Glenn A; Sweeney, H Lee; Vandenborne, Krista

    2018-01-01

    To provide evidence for quantitative magnetic resonance (qMR) biomarkers in Duchenne muscular dystrophy by investigating the relationship between qMR measures of lower extremity muscle pathology and functional endpoints in a large ambulatory cohort using a multicenter study design. MR spectroscopy and quantitative imaging were implemented to measure intramuscular fat fraction and the transverse magnetization relaxation time constant (T2) in lower extremity muscles of 136 participants with Duchenne muscular dystrophy. Measures were collected at 554 visits over 48 months at one of three imaging sites. Fat fraction was measured in the soleus and vastus lateralis using MR spectroscopy, while T2 was assessed using MRI in eight lower extremity muscles. Ambulatory function was measured using the 10m walk/run, climb four stairs, supine to stand, and six minute walk tests. Significant correlations were found between all qMR and functional measures. Vastus lateralis qMR measures correlated most strongly to functional endpoints (|ρ| = 0.68-0.78), although measures in other rapidly progressing muscles including the biceps femoris (|ρ| = 0.63-0.73) and peroneals (|ρ| = 0.59-0.72) also showed strong correlations. Quantitative MR biomarkers were excellent indicators of loss of functional ability and correlated with qualitative measures of function. A VL FF of 0.40 was an approximate lower threshold of muscle pathology associated with loss of ambulation. Lower extremity qMR biomarkers have a robust relationship to clinically meaningful measures of ambulatory function in Duchenne muscular dystrophy. These results provide strong supporting evidence for qMR biomarkers and set the stage for their potential use as surrogate outcomes in clinical trials.

  13. Platelet-Derived Growth Factor BB Influences Muscle Regeneration in Duchenne Muscle Dystrophy.

    Science.gov (United States)

    Piñol-Jurado, Patricia; Gallardo, Eduard; de Luna, Noemi; Suárez-Calvet, Xavier; Sánchez-Riera, Carles; Fernández-Simón, Esther; Gomis, Clara; Illa, Isabel; Díaz-Manera, Jordi

    2017-08-01

    Duchenne muscular dystrophy (DMD) is characterized by a progressive loss of muscle fibers, and their substitution by fibrotic and adipose tissue. Many factors contribute to this process, but the molecular pathways related to regeneration and degeneration of muscle are not completely known. Platelet-derived growth factor (PDGF)-BB belongs to a family of growth factors that regulate proliferation, migration, and differentiation of mesenchymal cells. The role of PDGF-BB in muscle regeneration in humans has not been studied. We analyzed the expression of PDGF-BB in muscle biopsy samples from controls and patients with DMD. We performed in vitro experiments to understand the effects of PDGF-BB on myoblasts involved in the pathophysiology of muscular dystrophies and confirmed our results in vivo by treating the mdx murine model of DMD with repeated i.m. injections of PDGF-BB. We observed that regenerating and necrotic muscle fibers in muscle biopsy samples from DMD patients expressed PDGF-BB. In vitro, PDGF-BB attracted myoblasts and activated their proliferation. Analysis of muscles from the animals treated with PDGF-BB showed an increased population of satellite cells and an increase in the number of regenerative fibers, with a reduction in inflammatory infiltrates, compared with those in vehicle-treated mice. Based on our results, PDGF-BB may play a protective role in muscular dystrophies by enhancing muscle regeneration through activation of satellite cell proliferation and migration. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy

    Science.gov (United States)

    2014-01-01

    -driven dystrophy progression and aberrant regeneration. PMID:25157321

  15. [Educational and Professional Qualifications of Adults With Myotonic Dystrophies - A Misleading Perception by the Myopathic Face?].

    Science.gov (United States)

    Stahl, K; Wenninger, S; Schüller, A; Montagnese, F; Schoser, B

    2016-04-01

    Myotonic dystrophies types 1 and 2 (DM1 / DM2) are the most frequent inherited progressive, segmental progeroid, multisystemic neuromuscular diseases in adulthood. The executive impairment is one of the key disease features. The myopathic face triggers the general perception of DM1 patients being associated with a low educational level. We used a standardized questionnaire to evaluate educational levels in adults with genetically confirmed DM1 and DM2 in comparison to data of the general population. Investigated topics included the level of education, e. g. the highest university degree aquired. Out of a total cohort of 546 DM patients, 125 DM1 and 156 DM2 patients (51 %) participated in this study. There was no statistically significant difference between the two collectives as far as high school levels are concerned. 50.4 % of DM1 and 48.3 % of DM2 patients obtained the higher education entrance qualification compared to 29.6 % of the normal German population. However, there were significant differences between the two collectives in "spelling problems" (DM1 cohort: p = 0.039), "difficulty in mental arithmetic" (p = 0.043), and classification of patients "with learning difficulties" (p = 0.012). Misled by a myopathic face, many physicians associate myotonic dystrophy with cognitive deficiency. Based on our study, the minimal deviation between DM1 and DM2 and the normal German population indicates that the multisystemic disease does not significantly influence the maximum attainable level of education in adults with DM1. In summary, physicians should be aware that the general educational levels are rather normal in patients with myotonic dystrophy type 1 and rethink their perception of DM1 patients. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Correlates of care for young men with Duchenne and Becker muscular dystrophy.

    Science.gov (United States)

    Andrews, Jennifer G; Davis, Melinda F; Meaney, F John

    2014-01-01

    In progressive conditions, such as Duchenne and Becker muscular dystrophy (DBMD), the need for care may outpace care use. We examined correlates that contribute to utilization of needed care. Structured interviews were conducted on use of care among 34 young men with DBMD who were born before 1982. Disease severity, per capita income, and presence of other relatives with DBMD predicted greater use of services. Race/ethnicity, acculturation, and level of caregiver education did not significantly predict service utilization. We identified disparities in receipt of healthcare and related services in adult men with DBMD that can affect quality of life. Despite the high disease severity identified in this population, these men utilized only half of the services available to individuals with significant progressive conditions. Providers should be aware of low service utilization and focus on awareness and assistance to ensure access to available care. Copyright © 2013 Wiley Periodicals, Inc.

  17. Creatine kinase response to high-intensity aerobic exercise in adult-onset muscular dystrophy

    DEFF Research Database (Denmark)

    Andersen, Søren P; Sveen, Marie-Louise; Hansen, Regitze S

    2013-01-01

    We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies.......We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies....

  18. Myocardial perfusion SPECT imaging in patients with myocardial bridging

    International Nuclear Information System (INIS)

    Fang Wei; Qiu Hong; Yang Weixian; Wang Feng; He Zuoxiang

    2008-01-01

    Objective: Stress myocardial perfusion SPECT imaging was used to assess myocardial ischemia in patients with myocardial bridging. Methods: Ninety-six patients with myocardial bridging of the left anterior descending artery documented by coronary angiography were included in this study. All under- went exercise or pharmacological stress myocardial perfusion SPECT assessing myocardial ischemia. None had prior myocardial infarction. One year follow-up by telephone interview was performed in all patients. Results The mean stenotic severity of systolic phase on angiography was (65 ± 19)%. In the SPECT study, 20 of 96 (20.8%) patients showed abnormal perfusion. This percentage was significantly higher than that of stress electrocardiogram (ECG). The higher positive rate of SPECT perfusion images was showed in the group of patients with severe systolic narrowing (≥75%) than that with mild-to-moderate systolic narrowing (50% vs 6.3%, P<0.001). The prevalence of abnormal image was significantly higher in ELDERLY PEOPLE; patients with STT change on rest ECG than in those with normal rest ECG (54.2% vs 9.7%, P<0.001). During follow-up, one patient with abnormal SPECT perfusion image sustained angina and accepted percutaneous coronary intervention, and no cardiac event occurred in patients with normal images. Conclusions: Stress myocardial perfusion SPECT imaging can be used effectively for assessing myocardial ischemia and has potential prognostic value for patients with myocardial bridging. (authors)

  19. Identification of a Novel Homozygous Nonsense Mutation Confirms the Implication of GNAT1 in Rod-Cone Dystrophy.

    Directory of Open Access Journals (Sweden)

    Cécile Méjécase

    Full Text Available GNAT1, encoding the transducin subunit Gα, is an important element of the phototransduction cascade. Mutations in this gene have been associated with autosomal dominant and autosomal recessive congenital stationary night blindness. Recently, a homozygous truncating GNAT1 mutation was identified in a patient with late-onset rod-cone dystrophy. After exclusion of mutations in genes underlying progressive inherited retinal disorders, by targeted next generation sequencing, a 32 year-old male sporadic case with severe rod-cone dystrophy and his unaffected parents were investigated by whole exome sequencing. This led to the identification of a homozygous nonsense variant, c.963C>A p.(Cys321* in GNAT1, which was confirmed by Sanger sequencing. The mother was heterozygous for this variant whereas the variant was absent in the father. c.963C>A p.(Cys321* is predicted to produce a shorter protein that lacks critical sites for the phototransduction cascade. Our work confirms that the phenotype and the mode of inheritance associated with GNAT1 variants can vary from autosomal dominant, autosomal recessive congenital stationary night blindness to autosomal recessive rod-cone dystrophy.

  20. A gene for late-onset fundus flavimaculatus with macular dystrophy maps to chromosome 1p13

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, S.; Rozet, J.M.; Bonneau, D.; Souied, E.; Camuzat, A.; Munnich, A.; Kaplan, J. [Hopital des Enfants Malades, Paris (France); Dufier, J.L. [Hopital Laeennec, Paris (France); Amalric, P. [Consultation d`Ophtalmologie, Albi (France); Weissenbach, J. [Genethon, Evry (France)

    1995-02-01

    Fundus flavimaculatus with macular dystrophy is an autosomal recessive disease responsible for a progressive loss of visual acuity in adulthood, with pigmentary changes of the macula, perimacular flecks, and atrophy of the retinal pigmentary epithelium. Since this condition shares several clinical features with Stargardt disease, which has been mapped to chromosome 1p21-p13, we tested the disease for linkage to chromosome 1p. We report the mapping of the disease locus to chromosome 1p13-p21, in the genetic interval defined by loci D1S435 and D1S415, in four multiplex families (maximum lod score 4.79 at recombination fraction 0 for probe AFM217xb2 at locus D1S435). Thus, despite differences in the age at onset, clinical course, and severity, fundus flavimaculatus with macular dystrophy and Stargardt disease are probably allelic disorders. This result supports the view that allelic mutations produce a continuum of macular dystrophies, with onset in early childhood to late adulthood. 16 refs., 3 figs., 1 tab.

  1. FHL1 reduces dystrophy in transgenic mice overexpressing FSHD muscular dystrophy region gene 1 (FRG1.

    Directory of Open Access Journals (Sweden)

    Sandra J Feeney

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is an autosomal-dominant disease with no effective treatment. The genetic cause of FSHD is complex and the primary pathogenic insult underlying the muscle disease is unknown. Several disease candidate genes have been proposed including DUX4 and FRG1. Expression analysis studies of FSHD report the deregulation of genes which mediate myoblast differentiation and fusion. Transgenic mice overexpressing FRG1 recapitulate the FSHD muscular dystrophy phenotype. Our current study selectively examines how increased expression of FRG1 may contribute to myoblast differentiation defects. We generated stable C2C12 cell lines overexpressing FRG1, which exhibited a myoblast fusion defect upon differentiation. To determine if myoblast fusion defects contribute to the FRG1 mouse dystrophic phenotype, this strain was crossed with skeletal muscle specific FHL1-transgenic mice. We previously reported that FHL1 promotes myoblast fusion in vitro and FHL1-transgenic mice develop skeletal muscle hypertrophy. In the current study, FRG1 mice overexpressing FHL1 showed an improvement in the dystrophic phenotype, including a reduced spinal kyphosis, increased muscle mass and myofiber size, and decreased muscle fibrosis. FHL1 expression in FRG1 mice, did not alter satellite cell number or activation, but enhanced myoblast fusion. Primary myoblasts isolated from FRG1 mice showed a myoblast fusion defect that was rescued by FHL1 expression. Therefore, increased FRG1 expression may contribute to a muscular dystrophy phenotype resembling FSHD by impairing myoblast fusion, a defect that can be rescued by enhanced myoblast fusion via expression of FHL1.

  2. Cardiac Involvement in Myotonic Dystrophy Type 2 Patients With Preserved Ejection Fraction: Detection by Cardiovascular Magnetic Resonance.

    Science.gov (United States)

    Schmacht, Luisa; Traber, Julius; Grieben, Ulrike; Utz, Wolfgang; Dieringer, Matthias A; Kellman, Peter; Blaszczyk, Edyta; von Knobelsdorff-Brenkenhoff, Florian; Spuler, Simone; Schulz-Menger, Jeanette

    2016-07-01

    Myotonic dystrophy type 2 (DM2) is a genetic disorder characterized by skeletal muscle symptoms, metabolic changes, and cardiac involvement. Histopathologic alterations of the skeletal muscle include fibrosis and fatty infiltration. The aim of this study was to investigate whether subclinical cardiac involvement in DM2 is already detectable in preserved left ventricular function by cardiovascular magnetic resonance. Twenty-seven patients (mean age, 54±10 years; 20 females) with a genetically confirmed diagnosis of DM2 were compared with 17 healthy age- and sex-matched controls using a 1.5 T magnetic resonance imaging. For myocardial tissue differentiation, T1 and T2 mapping, fat/water-separated imaging, focal fibrosis imaging (late gadolinium enhancement [LGE]), and (1)H magnetic resonance spectroscopy were performed. Extracellular volume fraction was calculated. Conduction abnormalities were diagnosed based on Groh criteria. LGE located subepicardial basal inferolateral was detectable in 22% of the patients. Extracellular volume was increased in this region and in the adjacent medial inferolateral segment (P=0.03 compared with healthy controls). In 21% of patients with DM2, fat deposits were detectable (all women). The control group showed no abnormalities. Myocardial triglycerides were not different in LGE-positive and LGE-negative subjects (P=0.47). Six patients had indicators for conduction disease (60% of LGE-positive patients and 12.5% of LGE-negative patients). In DM2, subclinical myocardial injury was already detectable in preserved left ventricular ejection fraction. Extracellular volume was also increased in regions with no focal fibrosis. Myocardial fibrosis was related to conduction abnormalities. © 2016 American Heart Association, Inc.

  3. Mothers' psychological adaptation to Duchenne/Becker muscular dystrophy

    Science.gov (United States)

    Peay, Holly L; Meiser, Bettina; Kinnett, Kathleen; Furlong, Pat; Porter, Kathryn; Tibben, Aad

    2016-01-01

    Duchenne and Becker muscular dystrophy (DBMD) cause significant emotional and care-related burden on caregivers, but no studies have evaluated predictors of positive caregiver outcomes, including disorder-specific psychological adaptation. Using a community-engaged approach focused on supporting mothers in positive aspects of caregiving, this prospective study aims to assess (i) the association between child's baseline functional status and mothers' illness perceptions, resilience, and coping self-efficacy; and (ii) predictors of mothers' psychological adaptation to caring for a child with DBMD. Biological mothers with at least one living child with DBMD completed a baseline survey (n=205) with 1-year (n=147) and 2-year (n=144) follow-up surveys. Worse child's baseline function was associated not only with increased caregiver burden and reduced maternal resilience, but also with perception of positive disease impact on the family. At two follow-ups, increased psychological adaptation to DBMD was predicted by resilience (β=0.264, P=0.001) and perceived positive impact (β=0.310, P<0.001), controlling for mother's age (β=−0.305, P<0.001) and income (β=−0.088, P=0.245). Child's functional status and caregiver burden of DBMD did not predict DBMD-specific adaptation. Though clinicians caring for families with DBMD should anticipate increased caregiver burden as the disorder progresses, interventions focused on caregiver burden are not expected to influence mothers' psychosocial adaptation. Efforts to improve mothers' well-being should focus on fostering mothers' resilience and enhancing perceptions of positive disease impact (benefit finding). Results suggest that psychosocial interventions can highlight strengths and well-being rather than burden and deficit. PMID:26306645

  4. Current Translational Research and Murine Models For Duchenne Muscular Dystrophy

    Science.gov (United States)

    Rodrigues, Merryl; Echigoya, Yusuke; Fukada, So-ichiro; Yokota, Toshifumi

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration. Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability. Currently, there is no cure for DMD. Since murine models are relatively easy to genetically manipulate, cost effective, and easily reproducible due to their short generation time, they have helped to elucidate the pathobiology of dystrophin deficiency and to assess therapies for treating DMD. Recently, several murine models have been developed by our group and others to be more representative of the human DMD mutation types and phenotypes. For instance, mdx mice on a DBA/2 genetic background, developed by Fukada et al., have lower regenerative capacity and exhibit very severe phenotype. Cmah-deficient mdx mice display an accelerated disease onset and severe cardiac phenotype due to differences in glycosylation between humans and mice. Other novel murine models include mdx52, which harbors a deletion mutation in exon 52, a hot spot region in humans, and dystrophin/utrophin double-deficient (dko), which displays a severe dystrophic phenotype due the absence of utrophin, a dystrophin homolog. This paper reviews the pathological manifestations and recent therapeutic developments in murine models of DMD such as standard mdx (C57BL/10), mdx on C57BL/6 background (C57BL/6-mdx), mdx52, dystrophin/utrophin double-deficient (dko), mdxβgeo, Dmd-null, humanized DMD (hDMD), mdx on DBA/2 background (DBA/2-mdx), Cmah-mdx, and mdx/mTRKO murine models. PMID:27854202

  5. Functions of fukutin, a gene responsible for Fukuyama type congenital muscular dystrophy, in neuromuscular system and other somatic organs.

    Science.gov (United States)

    Yamamoto, Tomoko; Shibata, Noriyuki; Saito, Yoshiaki; Osawa, Makiko; Kobayashi, Makio

    2010-06-01

    Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive disease, exhibiting muscular dystrophy, and central nervous system (CNS) and ocular malformations. It is included in alpha-dystroglycanopathy, a group of muscular dystrophy showing reduced glycosylation of alpha-dystroglycan. alpha-Dystroglycan is one of the components of dystrophin-glycoprotein complex linking extracellular and intracellular proteins. The sugar chains of alpha-dystroglycan are receptors for extracellular matrix proteins such as laminin. Fukutin, a gene responsible for FCMD, is presumably related to the glycosylation of alpha-dystroglycan like other causative genes of alpha-dystroglycanopathy. The CNS lesion of FCMD is characterized by cobblestone lissencephaly, associated with decreased glycosylation of alpha-dystroglycan in the glia limitans where the basement membrane is formed. Astrocytes whose endfeet form the glia limitans seem to be greatly involved in the genesis of the CNS lesion. Fukutin is probably necessary for astrocytic function. Other components of the CNS may also need fukutin, such as migration and synaptic function in neurons. However, roles of fukutin in oligodendroglia, microglia, leptomeninges and capillaries are unknown at present. Fukutin is expressed in various somatic organs as well, and appears to work differently between epithelial cells and astrocytes. In the molecular level, since the dystrophin-glycoprotein complex is linked to cell signaling pathways involving c-src and c-jun, fukutin may be able to affect cell proliferation/survival. Fukutin was localized in the nucleus on cancer cell lines. With the consideration that mutations of fukutin give rise to wide spectrum of the clinical phenotype, more unknown functions of fukutin besides the glycosylation of alpha-dystroglycan can be suggested. Trials for novel treatments including gene therapy are in progress in muscular dystrophies. Toward effective therapies with minimal side effects, precise

  6. Distribution of skeletal muscle involvement in autosomal recessive distal muscular dystrophy

    International Nuclear Information System (INIS)

    Mizusawa, Hidehiro; Nakanishi, Takao; Kobayashi, Fumie.

    1987-01-01

    Distribution of skeletal muscle involvement in 5 cases with autosomal recessive distal muscular dystrophy was studied clinically and by computed tomography (CT). Manual muscle test showed muscle involvement with a predilection for flexors in the lower leg and adductors in the thigh. Flexion and extension of the thigh and the lower leg was impaired to similar degree. In progressed cases, neck flexors and trunk muscles were also affected mildly. CT disclosed more clearly the preferential involvement of flexors in the lower leg, and involvement of both hamstrings · adductors group and extensors group of the thigh to similar degree. However, m. popliteus was curiously well preserved. In addition, there was a stage showing high density and hypertrophy of m. sartorius, m. gracilis, m. adductor, m. biceps femoris, m. semimenbranosus, m. semitendinosus or m. rectus femoris, which in thought to be compensatory hypertrophy. M. gluteus minimus in the pelvic girdle and m. dorsi proprii in the trunk were also liable to be affected. The CT findings are regarded as characteristic features noted clearly before muscle weakness and atrophy become apparent clinically. CT is very useful for distinguishing distal muscular dystrophy from rimmed vacuolar distal myopathy in which m. quadriceps femoris and flexors of the lower leg are usually well preserved without compensatory hypertrophy on CT. (author)

  7. Diaphragm remodeling and compensatory respiratory mechanics in a canine model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Mead, A F; Petrov, M; Malik, A S; Mitchell, M A; Childers, M K; Bogan, J R; Seidner, G; Kornegay, J N; Stedman, H H

    2014-04-01

    Ventilatory insufficiency remains the leading cause of death and late stage morbidity in Duchenne muscular dystrophy (DMD). To address critical gaps in our knowledge of the pathobiology of respiratory functional decline, we used an integrative approach to study respiratory mechanics in a translational model of DMD. In studies of individual dogs with the Golden Retriever muscular dystrophy (GRMD) mutation, we found evidence of rapidly progressive loss of ventilatory capacity in association with dramatic morphometric remodeling of the diaphragm. Within the first year of life, the mechanics of breathing at rest, and especially during pharmacological stimulation of respiratory control pathways in the carotid bodies, shift such that the primary role of the diaphragm becomes the passive elastic storage of energy transferred from abdominal wall muscles, thereby permitting the expiratory musculature to share in the generation of inspiratory pressure and flow. In the diaphragm, this physiological shift is associated with the loss of sarcomeres in series (∼ 60%) and an increase in muscle stiffness (∼ 900%) compared with those of the nondystrophic diaphragm, as studied during perfusion ex vivo. In addition to providing much needed endpoint measures for assessing the efficacy of therapeutics, we expect these findings to be a starting point for a more precise understanding of respiratory failure in DMD.

  8. A computerized MRI biomarker quantification scheme for a canine model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Wang, Jiahui; Fan, Zheng; Vandenborne, Krista; Walter, Glenn; Shiloh-Malawsky, Yael; An, Hongyu; Kornegay, Joe N; Styner, Martin A

    2013-09-01

    Golden retriever muscular dystrophy (GRMD) is a widely used canine model of Duchenne muscular dystrophy (DMD). Recent studies have shown that magnetic resonance imaging (MRI) can be used to non-invasively detect consistent changes in both DMD and GRMD. In this paper, we propose a semiautomated system to quantify MRI biomarkers of GRMD. Our system was applied to a database of 45 MRI scans from 8 normal and 10 GRMD dogs in a longitudinal natural history study. We first segmented six proximal pelvic limb muscles using a semiautomated full muscle segmentation method. We then performed preprocessing, including intensity inhomogeneity correction, spatial registration of different image sequences, intensity calibration of T2-weighted and T2-weighted fat-suppressed images, and calculation of MRI biomarker maps. Finally, for each of the segmented muscles, we automatically measured MRI biomarkers of muscle volume, intensity statistics over MRI biomarker maps, and statistical image texture features. The muscle volume and the mean intensities in T2 value, fat, and water maps showed group differences between normal and GRMD dogs. For the statistical texture biomarkers, both the histogram and run-length matrix features showed obvious group differences between normal and GRMD dogs. The full muscle segmentation showed significantly less error and variability in the proposed biomarkers when compared to the standard, limited muscle range segmentation. The experimental results demonstrated that this quantification tool could reliably quantify MRI biomarkers in GRMD dogs, suggesting that it would also be useful for quantifying disease progression and measuring therapeutic effect in DMD patients.

  9. Dystrophic changes in masticatory muscles related chewing problems and malocclusions in Duchenne muscular dystrophy.

    Science.gov (United States)

    van den Engel-Hoek, L; de Groot, I J M; Sie, L T; van Bruggen, H W; de Groot, S A F; Erasmus, C E; van Alfen, N

    2016-06-01

    Dysphagia in Duchenne muscular dystrophy (DMD) worsens with age, with increasingly effortful mastication. The aims of this study were to describe mastication problems in consecutive stages in a group of patients with DMD and to determine related pathophysiological aspects of masticatory muscle structure, tongue thickness, bite force and dental characteristics. Data from 72 patients with DMD (4.3 to 28.0 years), divided into four clinical stages, were collected in a cross sectional study. Problems with mastication and the need for food adaptations, in combination with increased echogenicity of the masseter muscle, were already found in the early stages of the disease. A high percentage of open bites and cross bites were found, especially in the later stages. Tongue hypertrophy also increased over time. Increased dysfunction, reflected by increasingly abnormal echogenicity, of the masseter muscle and reduced occlusal contacts (anterior and posterior open bites) were mainly responsible for the hampered chewing. In all, this study shows the increasing involvement of various elements of the masticatory system in progressive Duchenne muscular dystrophy. To prevent choking and also nutritional deficiency, early detection of chewing problems by asking about feeding and mastication problems, as well as asking about food adaptations made, is essential and can lead to timely intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Pneumothoraces in collagen VI-related dystrophy: a case series and recommendations for management

    Directory of Open Access Journals (Sweden)

    Kristin L. Fraser

    2017-06-01

    Full Text Available Collagen VI-related dystrophy (collagen VI-RD is a rare neuromuscular condition caused by mutations in the COL6A1, COL6A2 or COL6A3 genes. The phenotypic spectrum includes early-onset Ullrich congenital muscular dystrophy, adult-onset Bethlem myopathy and an intermediate phenotype. The disorder is characterised by distal hyperlaxity and progressive muscle weakness, joint contractures and respiratory insufficiency. Respiratory insufficiency is attributed to chest wall contractures, scoliosis, impaired diaphragmatic function and intercostal muscle weakness. To date, intrinsic parenchymal lung disease has not been implicated in the inevitable respiratory decline of these patients. This series focuses on pneumothorax, an important but previously under-recognised disease manifestation of collagen VI-RD. We describe two distinct clinical presentations within collagen VI-RD patients with pneumothorax. The first cohort consists of neonates and children with a single pneumothorax in the setting of large intrathoracic pressure changes. The second group is made up of adult patients with recurrent pneumothoraces, associated with chest computed tomography scan evidence of parenchymal lung disease. We describe treatment challenges in this unique population with respect to expectant observation, tube thoracostomy and open pleurodesis. Based on this experience, we offer recommendations for early identification of lung disease in collagen VI-RD and definitive intervention.

  11. Efficacy and Safety Profile of Tricyclo-DNA Antisense Oligonucleotides in Duchenne Muscular Dystrophy Mouse Model

    Directory of Open Access Journals (Sweden)

    Karima Relizani

    2017-09-01

    Full Text Available Antisense oligonucleotides (AONs hold promise for therapeutic splice-switching correction in many genetic diseases. However, despite advances in AON chemistry and design, systemic use of AONs is limited due to poor tissue uptake and sufficient therapeutic efficacy is still difficult to achieve. A novel class of AONs made of tricyclo-DNA (tcDNA is considered very promising for the treatment of Duchenne muscular dystrophy (DMD, a neuromuscular disease typically caused by frameshifting deletions or nonsense mutations in the gene-encoding dystrophin and characterized by progressive muscle weakness, cardiomyopathy, and respiratory failure in addition to cognitive impairment. Herein, we report the efficacy and toxicology profile of a 13-mer tcDNA in mdx mice. We show that systemic delivery of 13-mer tcDNA allows restoration of dystrophin in skeletal muscles and to a lower extent in the brain, leading to muscle function improvement and correction of behavioral features linked to the emotional/cognitive deficiency. More importantly, tcDNA treatment was generally limited to minimal glomerular changes and few cell necroses in proximal tubules, with only slight variation in serum and urinary kidney toxicity biomarker levels. These results demonstrate an encouraging safety profile for tcDNA, albeit typical of phosphorothiate AONs, and confirm its therapeutic potential for the systemic treatment of DMD patients. Keywords: antisense oligonucleotides, Duchenne muscular dystrophy, preclinical, splice switching, tcDNA-AONs

  12. "The Things That Are inside of You Are Horrible": Children and Young Men with Duchenne Muscular Dystrophy Talk about the Impact of Living with a Long-Term Condition

    Science.gov (United States)

    Abbott, David; Carpenter, John

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an inherited, progressive and life-limiting neuromuscular disease that affects boys. During their lives, they experience a series of medical and surgical interventions. Research reported in this paper took place in England with 37 young men living with DMD and their families and explored their experiences of…

  13. Morphologic imaging in muscular dystrophies and inflammatory myopathies

    International Nuclear Information System (INIS)

    Degardin, Adrian; Lacour, Arnaud; Vermersch, Patrick; Morillon, David; Cotten, Anne; Stojkovic, Tanya

    2010-01-01

    To determine if magnetic resonance imaging (MR imaging) is useful in the diagnostic workup of muscular dystrophies and idiopathic inflammatory myopathies for describing the topography of muscle involvement. MR imaging was performed in 31 patients: 8 with dystrophic myotony types 1 (n = 4) or 2 (n = 4); 11 with limb-girdle muscular dystrophy, including dysferlinopathy, calpainopathy, sarcoglycanopathy, and dystrophy associated with fukutin-related protein mutation; 3 with Becker muscular dystrophy; and 9 with idiopathic inflammatory myopathies, including polymyositis, dermatomyositis, and sporadic inclusion body myositis. Analysis of T1 images enabled us to describe the most affected muscles and the muscles usually spared for each muscular disease. In particular, examination of pelvis, thigh, and leg muscles demonstrated significant differences between the muscular diseases. On STIR images, hyperintensities were present in 62% of our patients with muscular dystrophies. A specific pattern of muscular involvement was established for each muscular disease. Hyperintensities observed on STIR images precede fatty degeneration and are not specific for inflammatory myopathies. (orig.)

  14. Morphologic imaging in muscular dystrophies and inflammatory myopathies

    Energy Technology Data Exchange (ETDEWEB)

    Degardin, Adrian; Lacour, Arnaud; Vermersch, Patrick [CHU de Lille, Clinique neurologique, Lille (France); Morillon, David; Cotten, Anne [CHRU de Lille, Service de Radiologie Osteoarticulaire, Hopital Roger Salengro, Lille (France); Stojkovic, Tanya [G-H Pitie-Salpetriere, Institut de Myologie, Paris (France)

    2010-12-15

    To determine if magnetic resonance imaging (MR imaging) is useful in the diagnostic workup of muscular dystrophies and idiopathic inflammatory myopathies for describing the topography of muscle involvement. MR imaging was performed in 31 patients: 8 with dystrophic myotony types 1 (n = 4) or 2 (n = 4); 11 with limb-girdle muscular dystrophy, including dysferlinopathy, calpainopathy, sarcoglycanopathy, and dystrophy associated with fukutin-related protein mutation; 3 with Becker muscular dystrophy; and 9 with idiopathic inflammatory myopathies, including polymyositis, dermatomyositis, and sporadic inclusion body myositis. Analysis of T1 images enabled us to describe the most affected muscles and the muscles usually spared for each muscular disease. In particular, examination of pelvis, thigh, and leg muscles demonstrated significant differences between the muscular diseases. On STIR images, hyperintensities were present in 62% of our patients with muscular dystrophies. A specific pattern of muscular involvement was established for each muscular disease. Hyperintensities observed on STIR images precede fatty degeneration and are not specific for inflammatory myopathies. (orig.)

  15. Neurocognitive Profiles in Duchenne Muscular Dystrophy and Gene Mutation Site

    Science.gov (United States)

    D’Angelo, Maria Grazia; Lorusso, Maria Luisa; Civati, Federica; Comi, Giacomo Pietro; Magri, Francesca; Del Bo, Roberto; Guglieri, Michela; Molteni, Massimo; Turconi, Anna Carla; Bresolin, Nereo

    2011-01-01

    The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing. PMID:22000308

  16. Preimplantation genetic diagnosis associated to Duchenne muscular dystrophy.

    Science.gov (United States)

    Bianco, Bianca; Christofolini, Denise Maria; Conceição, Gabriel Seixas; Barbosa, Caio Parente

    2017-01-01

    Duchenne muscular dystrophy is the most common muscle disease found in male children. Currently, there is no effective therapy available for Duchenne muscular dystrophy patients. Therefore, it is essential to make a prenatal diagnosis and provide genetic counseling to reduce the birth of such boys. We report a case of preimplantation genetic diagnosis associated with Duchenne muscular dystrophy. The couple E.P.R., 38-year-old, symptomatic patient heterozygous for a 2 to 47 exon deletion mutation in DMD gene and G.T.S., 39-year-old, sought genetic counseling about preimplantation genetic diagnosis process. They have had a 6-year-old son who died due to Duchenne muscular dystrophy complications. The couple underwent four cycles of intracytoplasmic sperm injection (ICSI) and eight embryos biopsies were analyzed by polymerase chain reaction (PCR) for specific mutation analysis, followed by microarray-based comparative genomic hybridisation (array CGH) for aneuploidy analysis. Preimplantation genetic diagnosis revealed that two embryos had inherited the maternal DMD gene mutation, one embryo had a chromosomal alteration and five embryos were normal. One blastocyst was transferred and resulted in successful pregnancy. The other embryos remain vitrified. We concluded that embryo analysis using associated techniques of PCR and array CGH seems to be safe for embryo selection in cases of X-linked disorders, such as Duchenne muscular dystrophy.

  17. Acute myocardial infarction

    International Nuclear Information System (INIS)

    RISCHPLER, Christoph

    2016-01-01

    Inflammatory processes after myocardial infarction have gained major interest in recent cardiovascular research. It is believed that not only the degree of cell recruitment to the heart plays a pivotal role in the quality of wound healing after myocardial infarction, but also the balance between different types or even subtypes of cells. It is also this balance which is thought to control key processes in tissue repair, such as apoptosis and neoangiogenesis. In this paper, we aim to review imaging strategies (with a special focus on nuclear molecular imaging strategies) that target cells and processes involved in postischemic inflammation and that have a high potential to be translated into clinic or that are already being used and evaluated in humans.

  18. Thallium-201 myocardial imaging

    International Nuclear Information System (INIS)

    Wackers, F.J.Th.

    1980-01-01

    Three views are routinely obtained for 201 Tl scintigraphy: 0 0 anterior, 45 0 left-anterior-oblique, both views with the patient supine and a left-lateral view, with the patient lying on his right side. Following intravenous injection of 201 Tl, the scintiscans of a normal subject only demonstrate the left ventricle. In patients with normal myocardial perfusion, the left ventricle appears horseshoe or ovoid in shape. The central area of decreased activity represents the left ventricular cavity and is normal. The accumulation of 201 Tl in the normal left ventricle is usually homogeneous. However, some areas with apparent diminished uptake may occur in the normal subject. These variations of the normal image are discussed. The right ventricle, because of its smaller myocardial mass and relatively less 201 Tl accumulation per gram of tissue, is usually on a resting study not, or only faintly, visualized. However, following exercise, the right ventricle is clearly visualized. (Auth.)

  19. Cardiac pathologies in female carriers of Duchenne muscular dystrophy assessed by cardiovascular magnetic resonance imaging

    International Nuclear Information System (INIS)

    Schelhorn, Juliane; Schemuth, Haemi; Nensa, Felix; Nassenstein, Kai; Forsting, Michael; Schlosser, Thomas; Schoenecker, Anne; Neudorf, Ulrich; Schara, Ulrike

    2015-01-01

    Duchenne muscular dystrophy (DMD) is the most common and severe dystrophinopathy. DMD carriers rarely present with clinical symptoms, but may suffer from cardiac involvement. Because echocardiographic findings are inconsistent and cardiac magnetic resonance imaging (CMRI) data are limited, this study sought to investigate asymptomatic carriers for cardiac abnormalities using CMRI. Fifteen genetically confirmed DMD carriers (age, 32.3 ± 10.2 years) were prospectively examined on a 1.5T MR system. Cine, T2, and late-gadolinium-enhanced (LGE) images were acquired, and were evaluated in consensus by two experienced readers. Left ventricular (LV) parameters were analysed semiautomatically, normalized to BSA. Normalized LV end-diastolic volume was increased in 7 % (73.7 ± 16.8 ml/m 2 ; range, 48-116 ml/m 2 ) and normalized LV end-systolic volume in 20 % (31.5 ± 13.3 ml/m 2 ; range, 15-74 ml/m 2 ). EF was reduced in 33 % (58.4 ± 7.6 %; range, 37-69 %) and normalized LV myocardial mass in 80 % (40.5 ± 6.8 g/m 2 ; range, 31-55 g/m 2 ). In 80 %, regional myocardial thinning was detected in more than one segment. In 13 % and 40 %, apical-lateral accentuation of LV non-compaction was present. LGE was found in 60 % (midmyocardial inferolateral accentuation). Given the high frequency of cardiac pathologies detected by CMRI, regular cardiac risk assessment is advisable for DMD carriers. Besides clinical examination, CMRI is an excellent tool for this purpose. (orig.)

  20. Cardiac pathologies in female carriers of Duchenne muscular dystrophy assessed by cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Schelhorn, Juliane; Schemuth, Haemi; Nensa, Felix; Nassenstein, Kai; Forsting, Michael; Schlosser, Thomas [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Schoenecker, Anne; Neudorf, Ulrich [University Hospital Essen, Department of Pediatric Cardiology, Essen (Germany); Schara, Ulrike [University Hospital Essen, Department of Pediatric Neurology, Essen (Germany)

    2015-10-15

    Duchenne muscular dystrophy (DMD) is the most common and severe dystrophinopathy. DMD carriers rarely present with clinical symptoms, but may suffer from cardiac involvement. Because echocardiographic findings are inconsistent and cardiac magnetic resonance imaging (CMRI) data are limited, this study sought to investigate asymptomatic carriers for cardiac abnormalities using CMRI. Fifteen genetically confirmed DMD carriers (age, 32.3 ± 10.2 years) were prospectively examined on a 1.5T MR system. Cine, T2, and late-gadolinium-enhanced (LGE) images were acquired, and were evaluated in consensus by two experienced readers. Left ventricular (LV) parameters were analysed semiautomatically, normalized to BSA. Normalized LV end-diastolic volume was increased in 7 % (73.7 ± 16.8 ml/m{sup 2}; range, 48-116 ml/m{sup 2}) and normalized LV end-systolic volume in 20 % (31.5 ± 13.3 ml/m{sup 2}; range, 15-74 ml/m{sup 2}). EF was reduced in 33 % (58.4 ± 7.6 %; range, 37-69 %) and normalized LV myocardial mass in 80 % (40.5 ± 6.8 g/m{sup 2}; range, 31-55 g/m{sup 2}). In 80 %, regional myocardial thinning was detected in more than one segment. In 13 % and 40 %, apical-lateral accentuation of LV non-compaction was present. LGE was found in 60 % (midmyocardial inferolateral accentuation). Given the high frequency of cardiac pathologies detected by CMRI, regular cardiac risk assessment is advisable for DMD carriers. Besides clinical examination, CMRI is an excellent tool for this purpose. (orig.)

  1. Canine Models of Duchenne Muscular Dystrophy and Their Use in Therapeutic Strategies

    Science.gov (United States)

    Kornegay, Joe N.; Bogan, Janet R.; Bogan, Daniel J.; Childers, Martin K.; Li, Juan; Nghiem, Peter; Detwiler, David A.; Larsen, C. Aaron; Grange, Robert W.; Bhavaraju-Sanka, Ratna K.; Tou, Sandra; Keene, Bruce P.; Howard, James F.; Wang, Jiahui; Fan, Zheng; Schatzberg, Scott J.; Styner, Martin A.; Flanigan, Kevin M.; Xiao, Xiao; Hoffman, Eric P.

    2013-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which the loss of dystrophin causes progressive degeneration of skeletal and cardiac muscle. Potential therapies that carry substantial risk, such as gene and cell-based approaches, must first be tested in animal models, notably the mdx mouse and several dystrophin-deficient breeds of dogs, including golden retriever muscular dystrophy (GRMD). Affected dogs have a more severe phenotype, in keeping with that of DMD, so may better predict disease pathogenesis and treatment efficacy. We and others have developed various phenotypic tests to characterize disease progression in the GRMD model. These biomarkers range from measures of strength and joint contractures to magnetic resonance imaging. Some of these tests are routinely used in clinical veterinary practice, while others require specialized equipment and expertise. By comparing serial measurements from treated and untreated groups, one can document improvement or delayed progression of disease. Potential treatments for DMD may be broadly categorized as molecular, cellular, or pharmacologic. The GRMD model has increasingly been used to assess efficacy of a range of these therapies. While some of these studies have largely provided general proof-of-concept for the treatment under study, others have demonstrated efficacy using the biomarkers discussed. Importantly, just as symptoms in DMD vary among patients, GRMD dogs display remarkable phenotypic variation. While confounding statistical analysis in preclinical trials, this variation offers insight regarding the role that modifier genes play in disease pathogenesis. By correlating functional and mRNA profiling results, gene targets for therapy development can be identified. PMID:22218699

  2. Myocardial ischemia in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Lima Filho, Moyses de Oliveira; Figueiredo, Geraldo L.; Simoes, Marcus V.; Pyntia, Antonio O.; Marin Neto, Jose Antonio

    2000-01-01

    Myocardial ischemia in hypertrophic cardiomyopathy is multifactorial and explains the occurrence of angina, in about 50% of patients. The pathophysiology of myocardial ischemia may be explained by the increase of the ventricular mass and relative paucity of the coronary microcirculation; the elevated ventricular filling pressures and myocardial stiffness causing a compression of the coronary microvessels; the impaired coronary vasodilator flow reserve caused by anatomic and functional abnormalities; and the systolic compression of epicardial vessel (myocardial bridges). Myocardial ischemia must be investigated by perfusion scintigraphic methods since its presence influences the prognosis and has relevant clinical implications for management of patients. Patients with hypertrophic cardiomyopathy and documented myocardial ischemia usually need to undergo invasive coronary angiography to exclude the presence of concomitant atherosclerotic coronary disease. (author)

  3. Serum Creatinine Level: A Supplemental Index to Distinguish Duchenne Muscular Dystrophy from Becker Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Huili Zhang

    2015-01-01

    Full Text Available Background. To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn level reflects disease severity. Methods. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. Results. Serum Crn level had a strong inverse correlation with Vignos score by simple correlation (r=-0.793 and partial correlation analysis after adjustment for age, height, and weight (r=-0.791; both P<0.01. Serum Crn level was significantly higher in patients with in-frame than out-of-frame mutations (Z=-4.716, P<0.01 and in Becker muscular dystrophy (BMD patients than Duchenne muscular dystrophy (DMD patients at ages 4, 5, 7, and 9 yr (all P<0.0125. After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients (β=7.140, t=6.277, P<0.01. Conclusions. Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice.

  4. [Specific features of Becker Muscular Dystrophy patients and female carriers of Duchenne Muscular Dystrophy].

    Science.gov (United States)

    Magot, A; Mercier, S; Péréon, Y

    2015-12-01

    Becker muscular dystrophy (BMD) was first described in 1955 and linked to the DMD gene in 1987. Compared to Duchenne muscular dystrophy (DMD), clinical onset of BMD usually occurs after the age of 12 and wheelchair is required after the age of 16. BMD is characterized by generalized weakness first affecting limb girdle muscles, hypertrophy of the calves and cardiomyopathy in males. Some patients have only mild symptoms such as cramps or elevated serum creatine kinases (SCK) throughout all their lives. SCK levels are usually elevated. Muscle biopsy (immunohistochemistry or immunoblotting) shows a dystrophic pattern with abnormal dystrophin staining. Diagnosis is confirmed by DMD gene sequencing. Deletions or duplications of one or several exons are identified in the majority of cases. A multidisciplinary approach is recommended for the care management of these patients with a particular attention to the cardiomyopathy, which is typically responsible for death but can be prevented by specific treatment. X-linked dilated cardiomyopathies linked to DMD gene are a phenotypic continuum of BMD. Some female carriers of DMD mutations exhibit clinical symptoms of variable severity, often milder and beginning later than in males. The cardiomyopathy is the most frequent feature that should be especially monitored in these patients. Genetic counselling should be systematically proposed. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. Acute myocardial infarcts

    International Nuclear Information System (INIS)

    Just, H.

    1988-01-01

    Acute myocardial infarction is a major complication of stenosing coronary artery disease and constitutes the most frequent single cause of death. It is caused by thrombotic occlusion of one of the major epicardial coronary arterial branches in most cases. Sudden death due to ventricular fibrillation is responsible for the majority of early fatalities. In 60% of all fatal infarcts, death occurs within 1 h of the onset of pain. The final extension of myocardial necrosis is reached within 2-4 h. An integrated programme has therefore been developed for the supervision and treatment of patients suffering acute coronary attack; it has been shown that it can markedly lower infarct mortality. It includes mobile prehospital care, intensive care treatment in the hospital, and rehabilitative procedures for application during reconvalescence. Early antiarrhythmic treatment and myocardial reperfusion via fibrinolysis are the main therapeutic procedures in the earliest stage. In hospital an operating room and an operating team must be available round the clock for the performance of coronary angiography followed by percutaneous transluminal coronary angioplasty or bypass surgery, which can be safely carried out in the acute stage provided the indications are strictly observed. Mortality and morbidity can be significantly lowered and both life expectancy and quality of life can be remarkably improved. (orig.) [de

  6. Retinal pigment epithelial dystrophy in Briard dogs.

    Science.gov (United States)

    Lightfoot, R M; Cabral, L; Gooch, L; Bedford, P G; Boulton, M E

    1996-01-01

    The eyes of normal Briard dogs, Briards affected with inherited retinal pigment epithelial dystrophy (RPED) and a range of normal crossbred and beagle dogs were examined and the histopathology of RPED in the Briard was compared with the histopathological features of ageing in the normal canine retina. RPED was characterised by the accumulation of auto-fluorescent lipofuscin-like inclusions in the retinal pigment epithelium (RPE), which initially involved only non-pigmented RPE cells overlying the tapetum but subsequently spread to all pigmented RPE cells. Secondary neuro-retinal degeneration was characterised by a gradual loss of the outer nuclear layer and the subsequent atrophy and degeneration of the inner retina. The loss of primary photoreceptors in the peripheral retina was accompanied by the migration of photoreceptor nuclei and appeared to resemble severe changes due to ageing. Intra-vitreal radiolabelled leucine was used to examine the rate of turnover of the outer segments of the rods in some Briards, but no significant variations were found. The activity of acid phosphatase in RPE was assayed in vitro and showed comparable regional variations in Briard and crossbred dogs. The results suggest that RPED in the Briard is unlikely to be due either to an increased rate of turnover of rod outer segments (and thus an increased phagocytic load) or to a primary insufficiency of lysosomal enzyme.

  7. Bone mineral density in reflex sympathetic dystrophy

    International Nuclear Information System (INIS)

    Saghaphi, M.; Azarian, A.

    2002-01-01

    Objectives: Reflex Sympathetic Dystrophy (RSD) is a complex of symptoms that produce pain burning sensation, swelling, tenderness, autonomic and physical dysfunction in joint areas, particularly distal of a limb. Osteopenia or osteoporosis is an important finding that is produced gradually in involved limb. Three phase bone can scan help to diagnosis of RSD. The disease may be bilateral but is mostly unilateral. As it is believed that bone densitometry will show osteopenia more accurate than plain comparative radiographs of the involved limbs, we investigated in patients with RSD. Methods: During last three years, 8 patients with RSD were admitted. Bone mineral density was measured for 5 patients by DEXA method. The patients were 3 males and 2 females with age range of 20 to 48 years (mean 32 years). The involved areas were ankle and foot in 4, and wrist and hand in one patient. Results: Mean Bone Mineral Content (BMC) of 4 involved lower limbs were 475 +-73 grams comparing with 516+-72 grams of uninvolved limbs (p t h patient was not significant. conclusion: comparative bone mineral density in patients with RSD of the lower limbs contributes to more accurate diagnosis than plain radiographs

  8. [Posterior polymorphous dystrophy, case report and literature review].

    Science.gov (United States)

    Mendoza-Adam, G; Hernandez-Camarena, J C; Valdez-García, J E

    2015-09-01

    Posterior Polymorphous Dystrophy (DPP) is a rare posterior corneal dystrophy that is genetically transmitted as autosomal dominant. Corneal structures affected in this dystrophy are Descemet membrane and the endothelium. A case is presented on a 47 years old woman with no relevant history, with typical findings of DPP (vesicular and band lesions at the endothelium and posterior Descemet). To our knowledge there are no reported cases of DPP in Latin-American patients in the literature. The clinical manifestations in our patient were found to be very similar to the cases reported in other populations. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

    Directory of Open Access Journals (Sweden)

    Rosa Dolz-Marco

    2014-01-01

    Full Text Available Purpose: To report corneal findings in a familial case of the crystalline subtype of pre- Descemetic corneal dystrophy. Case Report: A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion: To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti΄s dystrophy and monoclonal gammopathy.

  10. Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

    Science.gov (United States)

    Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Pinazo-Durán, María Dolores; Díaz-Llopis, Manuel

    2014-01-01

    Purpose To report corneal findings in a familial case of the crystalline subtype of pre-Descemetic corneal dystrophy. Case Report A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti´s dystrophy and monoclonal gammopathy. PMID:25279130

  11. Chronic administration of a leupeptin-derived calpain inhibitor fails to ameliorate severe muscle pathology in a canine model of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Martin K Childers

    2012-01-01

    Full Text Available Calpains likely play a role in the pathogenesis of Duchenne muscular dystrophy (DMD. Accordingly, calpain inhibition may provide therapeutic benefit to DMD patients. In the present study, we sought to measure benefit from administration of a novel calpain inhibitor, C101, in a canine muscular dystrophy model. Specifically, we tested the hypothesis that treatment with C101 mitigates progressive weakness and severe muscle pathology observed in young dogs with golden retriever muscular dystrophy (GRMD. Young (6 week-old GRMD dogs were treated daily with either C101 (17mg/kg twice daily oral dose, n=9 or placebo (vehicle only, n=7 for 8 weeks. A battery of functional tests, including tibiotarsal joint angle, muscle/fat composition, and pelvic limb muscle strength were performed at baseline and every two weeks during the 8-week study. Results indicate that C101-treated GRMD dogs maintained strength in their cranial pelvic limb muscles (tibiotarsal flexors while placebo-treated dogs progressively lost strength. However, concomitant improvement was not observed in posterior pelvic limb muscles (tibiotarsal extensors. C101 treatment did not mitigate force drop following repeated eccentric contractions and no improvement was seen in the development of joint contractures, lean muscle mass or muscle histopathology. Taken together, these data do not support the hypothesis that treatment with C101 mitigates progressive weakness or ameliorates severe muscle pathology observed in young dogs with GRMD.

  12. In Vitro Contracture Test Results and Anaesthetic Management of a Patient with Emery-Dreifuss Muscular Dystrophy for Cardiac Transplantation

    Directory of Open Access Journals (Sweden)

    Frank Schuster

    2012-01-01

    Full Text Available Emery-Dreifuss muscular dystrophy (EDMD is a hereditary neuromuscular disorder characterized by slowly progressive muscle weakness, early contractures, and dilated cardiomyopathy. We reported an uneventful general anaesthesia using total intravenous anaesthesia (TIVA for cardiac transplantation in a 19-year-old woman suffering from EDMD. In vitro contracture test results of two pectoralis major muscle bundles of the patient suggest that exposition to triggering agents does not induce a pathological sarcoplasmic calcium release in the lamin A/C phenotype. However, due to the lack of evidence in the literature, we would recommend TIVA for patients with EDMD if general anaesthesia is required.

  13. Muscle regeneration and inflammation in patients with facioscapulohumeral muscular dystrophy

    DEFF Research Database (Denmark)

    Hauerslev, S; Ørngreen, M C; Hertz, J M

    2013-01-01

    The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A.......The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A....

  14. Intramuscular degeneration process in Duchenne muscular dystrophy; Investigation by longitudinal MR imaging of the skeletal muscles

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Takeshi; Matsumra, Kiichiro (Shimoshizu National Hospital, Yotsukaido, Chiba (Japan)); Hashimoto, Takahiro; Ikehira, Hiroo; Fukuda, Hiroshi; Tateno, Yukio

    1992-03-01

    Intramuscular degeneration process of Duchenne dystrophy skeletal muscles was investigated by longitudinal skeletal muscle imaging with high-field-strength NMR-CT of 1.5 Tesla. Thigh muscles in 10 cases ranging in age from 4 to 19 years were examined by T{sub 1}-weighted longitudinal images (TR=215{approx}505 ms, TE=19{approx}20 ms). The following results were obtained. Skeletal muscle degeneration was depicted as high signal intensity area reflecting its high fat contents. These high signal intensity areas had a longitudinally streaky appearance in parallel direction with myofibers. These findings were more prominent toward myotendon junction than muscle bellies. Skeletal muscle degeneration progressed rapidly between 7 to 10 years of age, and reached a plateau after that. (author).

  15. Duchenne muscular dystrophy diagnosed by dystrophin gene deletion test: A case report

    Directory of Open Access Journals (Sweden)

    Rathod Kishor G, Dawre Rahul M, Kamble Milind B,Tambe Saleem H

    2014-04-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disease affecting 1 in 3600—6000 live male births. A muscle biopsy is not necessary if a genetic diagnosis is secured first, particularly as some families might view the procedure as traumatic. DMD occurs as a result of mutations (mainly deletions in the dystrophin gene (DMD; locus Xp21.2. Mutations lead to an absence of or defect in the protein dystrophin, which results in progressive muscle degeneration leading to loss of independent ambulation. Ninety percent of out frame mutations result in DMD, while 90% of in-frame mutations result in BMD. Electron microscopy is not required to confirm DMD. Genetic testing is mandatory irrespective of biopsy results. But the muscle biopsy is not required if the diagnosis is secured first by genetic testing.

  16. Novel LMNA Mutation in a Taiwanese Family with Autosomal Dominant Emery-Dreifuss Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Wen-Chen Liang

    2007-01-01

    Full Text Available Emery-Dreifuss muscular dystrophy (EDMD is characterized by early-onset contractures, slowly progressive weakness, and muscle wasting in humeroperoneal muscles, and adult-onset cardiomyopathy with conduction block. We analyzed blood samples from an EDMD family, including a mother and two daughters, and found a novel mutation in codon 520 in exon 9 of the lamin A/C (LMNA gene, resulting in a substitution of tryptophan (W by glycine (G in all three patients. The mother died after a stroke-like episode at the age of 43. The elder sister received pacemaker implantation, which improved symptoms of exercise intolerance and dizziness. These cases illustrate the necessity of correct diagnosis, evaluation, and follow-up of cardiac problems due to the wide clinical spectrum and high prevalence of cardiac conduction block in patients with autosomal dominant EDMD. [J Formos Med Assoc 2007;106(2 Suppl:S27-S31

  17. Limb-girdle muscular dystrophy type 2A in Brazilian children

    Directory of Open Access Journals (Sweden)

    Marco Antônio Veloso de Albuquerque

    2015-12-01

    Full Text Available ABSTRACT Calpainopathy is an autosomal recessive limb girdle muscular dystrophy (LGMD2A caused by mutations in CAPN3 gene. Objective To present clinical and histological findings in six children with a molecular diagnosis of LGMD2A and additionally the MRI findings in two of them. Method We retrospectively assessed medical records of 6 patients with mutation on CAPN3 gene. Results All patients were female (three to 12 years. The mean of age of disease onset was 9 years. All of them showed progressive weakness with predominance in lower limbs. Other findings were scapular winging, joint contractures and calf hypertrophy. One female had a more severe phenotype than her dizygotic twin sister that was confirmed by muscle MRI. Muscle biopsies showed a dystrophic pattern in all patients. Conclusion In this cohort of children with LGMD2A, the clinical aspects were similar to adults with the same disorder.

  18. Musculoskeletal simulation can help explain selective muscle degeneration in Duchenne muscular dystrophy.

    Science.gov (United States)

    Hu, Xiao; Blemker, Silvia S

    2015-08-01

    Duchenne muscular dystrophy (DMD) is a genetic disease that occurs due to the deficiency of the dystrophin protein. Although dystrophin is deficient in all muscles, it is unclear why degeneration progresses differently across muscles in DMD. We hypothesized that each muscle undergoes a different degree of eccentric contraction during gait, which could contribute to the selective degeneration in lower limb muscle, as indicated by various amounts of fatty infiltration. By comparing eccentric contractions quantified from a previous multibody dynamic musculoskeletal gait simulation and fat fractions quantified in a recent imaging study, our preliminary analyses show a strong correlation between eccentric contractions during gait and lower limb muscle fat fractions, supporting our hypothesis. This knowledge is critical for developing safe exercise regimens for the DMD population. This study also provides supportive evidence for using multiscale modeling and simulation of the musculoskeletal system in future DMD research. © 2015 Wiley Periodicals, Inc.

  19. Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Irina T Zaharieva

    Full Text Available Duchenne muscular Dystrophy (DMD is an inherited disease caused by mutations in the dystrophin gene that disrupt the open reading frame, while in frame mutations result in Becker muscular dystrophy (BMD. Ullrich congenital muscular dystrophy (UCMD is due to mutations affecting collagen VI genes. Specific muscle miRNAs (dystromirs are potential non-invasive biomarkers for monitoring the outcome of therapeutic interventions and disease progression. We quantified miR-1, miR-133a,b, miR-206 and miR-31 in serum from patients with DMD, BMD, UCMD and healthy controls. MiR-1, miR-133a,b and miR-206 were upregulated in DMD, but unchanged in UCMD compared to controls. Milder DMD patients had higher levels of dystromirs than more severely affected patients. Patients with low forced vital capacity (FVC values, indicating respiratory muscle weakness, had low levels of serum miR-1 and miR-133b. There was no significant difference in the level of the dystromirs in BMD compared to controls. We also assessed the effect of dystrophin restoration on the expression of the five dystromirs in serum of DMD patients treated systemically for 12 weeks with antisense oligomer eteplirsen that induces skipping of exon 51 in the dystrophin gene. The dystromirs were also analysed in muscle biopsies of DMD patients included in a single dose intramuscular eteplirsen clinical trial. Our analysis detected a trend towards normalization of these miRNA between the pre- and post-treatment samples of the systemic trial, which however failed to reach statistical significance. This could possibly be due to the small number of patients and the short duration of these clinical trials. Although longer term studies are needed to clarify the relationship between dystrophin restoration following therapeutic intervention and the level of circulating miRNAs, our results indicate that miR-1 and miR-133 can be considered as exploratory biomarkers for monitoring the progression of muscle weakness

  20. Computed tomography in Duchenne type muscular dystrophy

    International Nuclear Information System (INIS)

    Kawai, Mitsuru; Kunimoto, Masanari; Motoyoshi, Yasufumi; Kuwata, Takashi; Nakano, Imaharu

    1985-01-01

    The computed tomography (CT) scan was performed on 91 Duchenne type muscular dystrophy (DMD) patients on the following four levels; (1) at the level of L3 vertebra, (2) 2-3cm above the symphysis pubica, (3) midposition of the thigh, (4) largest-diameter section of the lower leg. The CT of muscles common to most of the DMD patients were as follows: 1. Muscle atrophy: Muscle atrophy was shown as a reduction in the cross-sectional area of the muscles. Very mild muscle atrophy could be detected either by the clearly identified muscle border or by scattered low-density areas of so-called ''moth-eaten'' appearance within muscles. 2. Fat infiltration: The decrease in radio-density of muscles was interpreted as infiltration of fatty tissue. This type of density change was further classified into diffuse, streaked, cobblestone and salt-and-pepper patterns according to the spacial distribution of low-density areas. 3. Selectivity pattern: As the chronological sequence of DMD muscle degeneration is usually different among individual muscles, it may be seen, in some stages, that some of the synergistic muscles are still only slightly involved, while the others are quite severely atrophied with evident fat infiltration. In certain stages of the disease, most of the patients show relative preservation of particular muscles although they assumed a rounded shape. The most resistent muscle was musculus gracilis, followed by the musculus sartorius, musculus semitendinosus (and/or musculus semimembranosus) in that order. According to the severity of the CT changes, 86 of the 91 patients were classed into five stages from A1 to A5. Morphological stages (A1-A5) were well correlated to the functional disability stages by Ueda with a correlation factor of r=0.88. (J.P.N.)

  1. Cardiac involvement in female Duchenne and Becker muscular dystrophy carriers in comparison to their first-degree male relatives: a comparative cardiovascular magnetic resonance study.

    Science.gov (United States)

    Florian, Anca; Rösch, Sabine; Bietenbeck, Michael; Engelen, Markus; Stypmann, Jörg; Waltenberger, Johannes; Sechtem, Udo; Yilmaz, Ali

    2016-03-01

    Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked recessive disorders associated with both skeletal myopathy and progressive cardiomyopathy in males. Female DMD/BMD carriers (DMDc/BMDc) are mostly free of skeletal muscle symptoms, but they are also prone to cardiomyopathy. The aim of the current study was to characterize the frequency, pattern, and extent of cardiomyopathy in female DMD/BMD carriers (DMDc/BMDc) in comparison to their first-degree male MD relatives. Thirty-six (age 44 ± 14 years) female MD carriers (20 DMDc and 16 BMDc) constituted the 'MD carrier group' and were prospectively enrolled. All MD carriers underwent a complete CMR study comprising cine- and late gadolinium enhancement (LGE) imaging. In 22 of these women ('female MD carrier comparison group', 7 DMD and 15 BMD), at least one first-degree male relative with a previously established diagnosis of MD underwent the same CMR protocol and was assigned to the 'male MD comparison group' (n = 24, 6 DMD and 18 BMD). In the total MD carrier group, 17 (47%) MD carriers had at least one pathological CMR finding [5 (14%) with a reduced left ventricular ejection fraction (LV-EF) and 16 (44%) with the presence of LGE]. All LGE-positive patients (n = 16) showed non-ischaemic LGE with subepicardial involvement of the LV lateral free wall being the most frequent pattern (13/16, 81%). Compared with BMDc, DMDc demonstrated more frequently a pathological CMR result (65 vs. 19%; P = 0.008)--in spite of being significantly younger (40 ± 11 vs. 50 ± 16 years, P = 0.038). In the male MD comparison group, the same LGE pattern as in female carriers was seen, but with a significantly higher prevalence of cardiac abnormalities compared with their female carrier relatives constituting the female MD comparison group (75 vs. 27%; P = 0.003). Cardiac involvement is a frequent finding in female carriers of DMD, but less frequently observed in carriers of BMD. Those DMDc and BMDc with cardiac involvement

  2. Granular Corneal Dystrophy Manifesting after Radial Keratotomy

    Directory of Open Access Journals (Sweden)

    Sepehr Feizi

    2008-12-01

    Full Text Available

    PURPOSE: To report manifestation of granular corneal dystrophy after radial keratotomy (RK. CASE REPORT: A 32-year-old man presented with white radial lines in both corneas. He had undergone uncomplicated RK in both eyes 8 years ago. Preoperative refraction had been OD: -3.5 -0.75@180 and OS: -3.0 -0.5@175. Uncorrected visual acuity was OD: 8/10 and OS: 7/10; best corrected visual acuity was 9/10 in both eyes with OD: -0.5 -0.5@60 and OS: -0.75 -0.5@80. Slit lamp examination revealed discrete well-demarcated whitish lesions with clear intervening stroma in the central anterior cornea consistent with granular dystrophy. Similar opacities were present within the RK incisions. CONCLUSION: Granular dystrophy deposits may appear within RK incisions besides other previously reported locations.

  1. [Changes in clinical condition and causes of death of inpatients with Duchenne muscular dystrophy in Japan from 1999 to 2012].

    Science.gov (United States)

    Saito, Toshio; Tatara, Katsunori; Kawai, Mitsuru

    2014-01-01

    To elucidate changes in medical treatment for Duchenne muscular dystrophy (DMD) in Japan, we analyzed the clinical courses and causes of death of inpatients with DMD registered in the muscular dystrophy ward database of 27 hospitals in Japan specializing in muscular dystrophy treatment since 1999. The total number of hospitalized cases in 1999 was 873, which gradually reduced to 733 in 2012. The mean age of DMD patients in 1999 was 23.6 years old, while that was 30.1 years old in 2012, with patients 40 years and older accounting for 94 cases in the latest year. The respirator dependent rate gradually increased from 58.6% in 1999 to 86.1% in 2012. Artificial respiration therapy was introduced earlier in more recent years and the mean age in recent years was shown to be 17.2 years old. The oral nutritional supply rate in 1999 was 95.1%, which fell to 66.8% in 2012, while gastrostomy feeding gradually increased to 129 cases in 2012. The rate of clinical diagnosis of DMD was 52.3% in 1999 and decreased to 43.7% in 2012, which showed progress towards more accurate diagnosis of DMD. From 2000 to 2012, 521 deaths were reported, with approximately half of the causes heart related, followed by respiratory related. The mean age of death gradually increased to 32.4 years old in 2012 from 26.7 years old in 2000. The mean age of survival of all DMD patients was 37.5 years old. Progress in multidisciplinary medical care for respiratory failure, cardiomyopathy, nutritional problems, and other related factors has extended the lifespan of DMD patients.

  2. Limb-girdle muscular dystrophy in Brazilian children: clinical, histological and molecular characterization

    Directory of Open Access Journals (Sweden)

    Marco A. Veloso Albuquerque

    2014-06-01

    Full Text Available Limb-girdle muscular dystrophies (LGMD are a heterogeneous group of genetic muscular dystrophies, involving 16 autosomal recessive subtypes and eight autosomal dominant subtypes. Autosomal recessive dystrophy is far more common than autosomal dominant dystrophy, particularly in children. The clinical course in this group is characterized by progressive proximal weakness, initially in pelvic and after in shoulder-girdle musculature, varying from very mild to severe degree. Significant overlap of clinical phenotypes, with genetic and clinical heterogeneity, constitutes the rule for this group of diseases. Muscle biopsies are useful for histopathologic and immunolabeling studies, and DNA analysis is the gold standard to establish the specific form of muscular dystrophy. Objectives: The aim of this study was to characterize the clinical, histological and molecular aspects in children with LGMD who attend a big public neuromuscular centre in our country to determine the frequency of different forms. Method: Thirty seven patients were classified as LGMD and included in this analysis. The study period extended from 2009-2012. The female to male ratio was 3:1. The age of onset ranged from two to 13 years, mean 7,5 years. Onset in the first decade was seen in 90%. Results: The initial clinical signs included: frequent falls (22 cases, difficulty in climbing stairs (13 cases, walk on tip toes (2 cases, difficulty in rising from the floor (2 cases and difficulty on walking (1 case. The serum CK levels were high in all cases. Among the 37 patients, 15 (40,5% were classified as sarcoglycanopathies (LGMD2C-F, five (13,5% as dysferlinopathy (LGMD2B, five (13,5% as calpainopathy (LGMD2A. Mutations in LMNA gene (LGMD1B, FKRP gene (LGMDI and caveolin gene (LGMD 1C were identified in two (5,5%, two (5,5% and one patient (2,5%, respectively. In seven of 37 cases (19% it was impossible to determine specific diagnosis. Calf hypertrophy, scapular winging and scoliosis

  3. An experimental study of BIGH3 gene mutations in the patients with corneal dystrophies

    International Nuclear Information System (INIS)

    Jin Tao; Zou Liuhe; Yang Ling

    2004-01-01

    Objective: To evaluate BIGH3 gene mutations in Chinese patents with corneal dystrophies. Methods: 2ml peripheral venous blood was collected from 15 patients with granular corneal dystrophies and 5 normal subjects. Leucocytes DNA was extracted with standard method. With two pairs of oligonucleotide primers, exon 4 and exon 12 of the BIGH3 gene were amplified using the polymerase chain reaction. Amplified DNA fragments were purified and sequenced directly. Results: Mutations in BIGH3 gene were detected in all the patients with corneal dystrophies. BIGH3 gene mutations were not found in normal subjects. 12 patients with Avellino corneal dystrophy had the missense mutation R124H in the BIGH3 gene. 3 patients with granular corneal dystrophy had the missense mutation R555W in the BIGH3 gene. Conclusion: R124H and R555W mutations in BIGH3 gene were also found in the Chinese patients with Avellino and granular corneal dystrophies. In China, Avellino corneal dystrophy associated with the R124H mutation is the most common form in the corneal dystrophies resulted by BIGH3 gene mutions. Condon 124 and 555 are also the hot spots for the mutations in the BIGH3 gene in the Chinese patients with corneal dystrophies. Molecular genetic analysis may be repuired for proper diagnosis and subclassification of corneal dystrophies. (authors)

  4. Stem cell transplantation for treating Duchenne muscular dystrophy

    Science.gov (United States)

    Yang, Xiaofeng

    2012-01-01

    OBJECTIVE: To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) publication between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to subject areas; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) distribution according to institution in China; (7) distribution according to institution that cooperated with Chinese institutions; (8) top-cited articles from 2002 to 2006; (9) top-cited articles from 2007 to 2011. RESULTS: A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation

  5. Myocardial perfusion abnormality and chest pain in patients with hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi; Murano, Kenichi; Usami, Masahisa

    1991-01-01

    To investigate the role of myocardial ischemia in the development of chest pain in patients with hypertrophic cardiomyopathy (HCM), exercise stress (Ex) redistribution myocardial single photon emission CT's (SPECT's) with thallium-201 (Tl) were obtained in 27 patients with HCM. In all patients, coronary arteries were normal arteriographically. Patients were classified into NYHA Class I, II and III according to the frequency and severity of the chest pain during daily life. In these 3 groups, age, sex and intraventricular septal thickness measured by echocardiography were not different. Types of myocardial perfusion obtained by myocardial SPECT's were divided into 5: (1) normal perfusion, (2) no perfusion defect with abnormal myocardial Tl washout rate (WOR) during 3 hours (<30%) [Def(-)/WORabn], (3) reversible perfusion defect (RD), (4) fixed defect with abnormal WOR (FD/WORabn), and (5) fixed defect with normal WOR (FD/WORnl). In 14 patients of Class I, 9 patients (64%) showed normal perfusion but the rest showed perfusion abnormality (def(-)/WORabn in 3 and RD in 2). In Class II and III, all patients showed perfusion abnormalities of RD, FD/WORabn or FD/WORnl. As the functional class progressed from Class II to III, the ratio of fixed defect (both WORnl and WORabn) to RD increased, but it was not statistically significant. In 2 patients in whom Ex SPECT's were repeated because of the progression of the chest pain, the severity of the perfusion abnormality also progressed. Perfusion abnormalities were observed most frequently in anterior (35%), then inferior/posterior (20%) and septal wall (18%). The frequency of Ex induced ECG abnormalities (ST-depression or T wave changes) increased as the NYHA Class progressed (Class III vs I p<0.05). These findings suggested the following: chest pain in patients with HCM relates to the myocardial ischemia which may originate in the myocardial small arteries, and when the lesions progress myocardial necrosis may ensue. (author)

  6. High fat diet-induced glucose intolerance impairs myocardial function, but not myocardial perfusion during hyperaemia: a pilot study

    Directory of Open Access Journals (Sweden)

    van den Brom Charissa E

    2012-06-01

    Full Text Available Abstract Background Glucose intolerance is a major health problem and is associated with increased risk of progression to type 2 diabetes mellitus and cardiovascular disease. However, whether glucose intolerance is related to impaired myocardial perfusion is not known. The purpose of the present study was to study the effect of diet-induced glucose intolerance on myocardial function and perfusion during baseline and pharmacological induced hyperaemia. Methods Male Wistar rats were randomly exposed to a high fat diet (HFD or control diet (CD (n = 8 per group. After 4 weeks, rats underwent an oral glucose tolerance test. Subsequently, rats underwent (contrast echocardiography to determine myocardial function and perfusion during baseline and dipyridamole-induced hyperaemia (20 mg/kg for 10 min. Results Four weeks of HFD feeding resulted in glucose intolerance compared to CD-feeding. Contractile function as represented by fractional shortening was not altered in HFD-fed rats compared to CD-fed rats under baseline conditions. However, dipyridamole increased fractional shortening in CD-fed rats, but not in HFD-fed rats. Basal myocardial perfusion, as measured by estimate of perfusion, was similar in CD- and HFD-fed rats, whereas dipyridamole increased estimate of perfusion in CD-fed rats, but not in HFD-fed rats. However, flow reserve was not different between CD- and HFD-fed rats. Conclusions Diet-induced glucose intolerance is associated with impaired myocardial function during conditions of hyperaemia, but myocardial perfusion is maintained. These findings may result in new insights into the effect of glucose intolerance on myocardial function and perfusion during hyperaemia.

  7. The ultrasound-guided nerve blocks of abdominal wall contributed to anesthetic management of cholecystectomy in a patient with Becker muscular dystrophy without using muscle relaxants.

    Science.gov (United States)

    Iwata, Masato; Kuzumoto, Naoya; Akasaki, Yuka; Morioka, Masayo; Nakayama, Kana; Matsuzawa, Nobuyoshi; Kimoto, Katsuhiro; Shimomura, Toshiyuki

    2017-01-01

    Becker muscular dystrophy (BMD) is a progressive neuromuscular disorder caused by mutations in the dystrophin gene. The sensitivity to non-depolarizing muscle relaxant in a patient with muscle dystrophy is reportedly higher than that in normal individuals, and the duration of the effect is known to be prolonged. In this report, we present the case of a 58-year-old man with BMD who underwent laparoscopic cholecystectomy for symptomatic cholelithiasis under total intravenous anesthesia without the use of muscle-relaxant drugs and supplemented with regional anesthesia. Anesthesia was induced and maintained with propofol, remifentanil, and fentanyl; ultrasound-guided bilateral rectus sheath block (RSB) and right-sided subcostal transversus abdominis plane block (TAP) were performed. The procedure required conversion to open surgery because of hard conglutination; intraoperative and postoperative periods were uneventful. Adequate analgesia was maintained after extubation because of the effect of RSB and TAP.

  8. Identification of a gene expression core signature for Duchenne Muscular Dystrophy (DMD) via integrative analysis reveals novel potential compounds for treatment

    KAUST Repository

    Ichim-Moreno, Norú

    2010-05-01

    Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy and one of the most prevalent genetic disorders of childhood. DMD is characterized by rapid progression of muscle degeneration, and ultimately death. Currently, glucocorticoids are the only available treatment for DMD, but they have been shown to result in serious side effects. The purpose of this research was to define a core signature of gene expression related to DMD via integrative analysis of mouse and human datasets. This core signature was subsequently used to screen for novel potential compounds that antagonistically affect the expression of signature genes. With this approach we were able to identify compounds that are 1) already used to treat DMD, 2) currently under investigation for treatment, and 3) so far unknown but promising candidates. Our study highlights the potential of meta-analyses through the combination of datasets to unravel previously unrecognized associations and reveal new relationships. © IEEE.

  9. Longitudinal Evaluation of Muscle Composition Using Magnetic Resonance in 4 Boys With Duchenne Muscular Dystrophy: Case Series.

    Science.gov (United States)

    Senesac, Claudia R; Lott, Donovan J; Forbes, Sean C; Mathur, Sunita; Arpan, Ishu; Senesac, Emily S; Walter, Glenn A; Vandenborne, Krista

    2015-07-01

    Duchenne muscular dystrophy (DMD), an inherited recessive X chromosome-linked disease, is the most severe childhood form of muscular dystrophy. Boys with DMD experience muscle loss, with infiltration of intramuscular fat into muscles. This case series describes the progression of DMD in boys using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Magnetic resonance results are then compared with an established functional timed test. Four boys with DMD and 4 healthy age-matched controls were chosen from a larger cohort. Boys with DMD were assessed at 4 time points over 2 years, with controls assessed at baseline only. Progression of the disease was documented by assessing the plantar flexors using MRI and MRS techniques and by assessing ambulation using the 30-Foot Fast Walk Test. Transverse relaxation time (T2) values were elevated in all boys with DMD at baseline. The lipid ratio increased rapidly as the disease progressed in 2 boys. Discrete changes in T2 in the other 2 boys with DMD indicated a slower disease progression. Magnetic resonance imaging and MRS allowed monitoring of the disease over all time periods regardless of ambulation status. The magnetic resonance data were collected with 2 different magnets at 2 different field strengths (1.5 and 3.0 T). Although we corrected for this difference, care must be taken in interpreting data when different image collection systems are used. This was a case series of 4 boys with DMD taken from a larger cohort study. Magnetic resonance imaging and MRS are objective, noninvasive techniques for measuring muscle pathology and can be used to detect discrete changes in both people who are ambulatory and those who are nonambulatory. These techniques should be considered when monitoring DMD progression and assessing efficacy of therapeutic interventions. © 2015 American Physical Therapy Association.

  10. Depression following myocardial infarction

    DEFF Research Database (Denmark)

    Larsen, Karen Kjær

    2013-01-01

    whether the mental burden of MI is so heavy that it increases the risk of suicide. Although post-MI depression is common and burdensome, the condition remains under-recognised and under-treated. The development of new strategies to improve the quality of care for people with post-MI depression requires...... between post-MI depression and new cardiovascular events or death, taking potential mediators into account (Paper III); 4. To examine the association between MI and suicide (Paper IV). Two different study designs were employed: a population-based cohort study using data obtained from registers......Myocardial infarction (MI) is a severe life event that is accompanied by an increased risk of depression. Mounting evidence suggests that post-MI depression is associated with adverse outcomes, but the underlying mechanisms of this association remain unclear, and no previous studies have examined...

  11. Myocardial late gadolinium enhancement in specific cardiomyopathies by cardiovascular magnetic resonance: a preliminary experience.

    Science.gov (United States)

    Silva, Caterina; Moon, James C; Elkington, Andrew G; John, Anna S; Mohiaddin, Raad H; Pennell, Dudley J

    2007-12-01

    Late gadolinium enhancement cardiovascular magnetic resonance (CMR) can visualize myocardial interstitial abnormalities. The aim of this study was to assess whether regions of abnormal myocardium can also be visualized by late enhancement gadolinium CMR in the specific cardiomyopathies. A retrospective review of all referrals for gadolinium CMR with specific cardiomyopathy over 20 months. Nine patients with different specific cardiomyopathies were identified. Late enhancement was demonstrated in all patients, with a mean signal intensity of 390 +/- 220% compared with normal regions. The distribution pattern of late enhancement was unlike the subendocardial late enhancement related to coronary territories found in myocardial infarction. The affected areas included papillary muscles (sarcoid), the mid-myocardium (Anderson-Fabry disease, glycogen storage disease, myocarditis, Becker muscular dystrophy) and the global sub-endocardium (systemic sclerosis, Loeffler's endocarditis, amyloid, Churg-Strauss). Focal myocardial late gadolinium enhancement is found in the specific cardiomyopathies, and the pattern is distinct from that seen in infarction. Further systematic studies are warranted to assess whether the pattern and extent of late enhancement may aid diagnosis and prognostic assessment.

  12. Development of Non-Hormonal Steroids for the Treatment of Duchenne Muscular Dystrophy

    Science.gov (United States)

    2013-02-01

    constructs envisioned in gene therapy, are also expressed in Becker muscular dystrophy (alleles of dystrophinopathy leading to milder disease). In other words...the Treatment of Duchenne Muscular Dystrophy PRINCIPAL INVESTIGATOR: Terence Partridge, PhD CONTRACTING ORGANIZATION: Children’s...Duchenne Muscular Dystrophy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0754 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Terence Partridge

  13. Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome)

    OpenAIRE

    Cacucci, Laura; Ricci, Beatrice; Moretti, Maria; Gasparini, Giulio; Pelo, Sandro; Grippaudo, Cristina

    2017-01-01

    Myotonic dystrophy, or Steinert’s disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewin...

  14. Longitudinal 2-point dixon muscle magnetic resonance imaging in becker muscular dystrophy.

    Science.gov (United States)

    Bonati, Ulrike; Schmid, Maurice; Hafner, Patricia; Haas, Tanja; Bieri, Oliver; Gloor, Monika; Fischmann, Arne; Fischer, Dirk

    2015-06-01

    Quantitative MRI techniques detect disease progression in myopathies more sensitively than muscle function measures or conventional MRI. To date, only conventional MRI data using visual rating scales are available for measurement of disease progression in Becker muscular dystrophy (BMD). In 3 patients with BMD (mean age 36.8 years), the mean fat fraction (MFF) of the thigh muscles was assessed by MRI at baseline and at 1-year follow-up using a 2-point Dixon approach (2PD). The motor function measurement scale (MFM) was used for clinical assessment. The mean MFF of all muscles at baseline was 61.6% (SD 7.6). It increased by 3.7% to 65.3% (SD 4.7) at follow-up. The severity of muscle involvement varied between various muscle groups. As in other myopathies, 2PD can quantify fatty muscle degeneration in BMD and can detect disease progression in a small sample size and at relatively short imaging intervals. © 2015 Wiley Periodicals, Inc.

  15. Correlation of circulating CD133+ progenitor subclasses with a mild phenotype in Duchenne muscular dystrophy patients.

    Directory of Open Access Journals (Sweden)

    Chiara Marchesi

    2008-05-01

    Full Text Available Various prognostic serum and cellular markers have been identified for many diseases, such as cardiovascular diseases and tumor pathologies. Here we assessed whether the levels of certain stem cells may predict the progression of Duchenne muscular dystrophy (DMD.The levels of several subpopulations of circulating stem cells expressing the CD133 antigen were determined by flow cytometry in 70 DMD patients. The correlation between the levels and clinical status was assessed by statistical analysis. The median (+/-SD age of the population was 10.66+/-3.81 (range 3 to 20 years. The levels of CD133+CXCR4+CD34- stem cells were significantly higher in DMD patients compared to healthy controls (mean+/-standard deviation: 17.38+/-1.38 vs. 11.0+/-1.70; P = 0.03 with a tendency towards decreased levels in older patients. Moreover, the levels of this subpopulation of cells correlated with the clinical condition. In a subgroup of 19 DMD patients after 24 months of follow-up, increased levels of CD133+CXCR4+CD34- cells was shown to be associated with a phenotype characterised by slower disease progression. The circulating CD133+CXCR4+CD34- cells in patients from different ages did not exhibit significant differences in their myogenic and endothelial in vitro differentiation capacity.Our results suggest that levels of CD133+CXCR4+CD34- could function as a new prognostic clinical marker for the progression of DMD.

  16. Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study.

    Directory of Open Access Journals (Sweden)

    Simina M Boca

    Full Text Available Serum metabolite profiling in Duchenne muscular dystrophy (DMD may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown compounds at m/z of 357 and 312 while decreased metabolites included creatinine, androgen derivatives and other unknown yet to be identified compounds. Furthermore, the creatine to creatinine ratio is significantly associated with disease progression in DMD patients. This ratio sharply increased with age in DMD patients while it decreased with age in healthy controls. Overall, this study yielded promising metabolic signatures that could prove useful to monitor DMD disease progression and response to therapies in the future.

  17. PKC theta ablation improves healing in a mouse model of muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Luca Madaro

    Full Text Available Inflammation is a key pathological characteristic of dystrophic muscle lesion formation, limiting muscle regeneration and resulting in fibrotic and fatty tissue replacement of muscle, which exacerbates the wasting process in dystrophic muscles. Limiting immune response is thus one of the therapeutic options to improve healing, as well as to improve the efficacy of gene- or cell-mediated strategies to restore dystrophin expression. Protein kinase C θ (PKCθ is a member of the PKCs family highly expressed in both immune cells and skeletal muscle; given its crucial role in adaptive, but also innate, immunity, it is being proposed as a valuable pharmacological target for immune disorders. In our study we asked whether targeting PKCθ could represent a valuable approach to efficiently prevent inflammatory response and disease progression in a mouse model of muscular dystrophy. We generated the bi-genetic mouse model mdx/θ(-/-, where PKCθ expression is lacking in mdx mice, the mouse model of Duchenne muscular dystrophy. We found that muscle wasting in mdx/θ(-/- mice was greatly prevented, while muscle regeneration, maintenance and performance was significantly improved, as compared to mdx mice. This phenotype was associated to reduction in inflammatory infiltrate, pro-inflammatory gene expression and pro-fibrotic markers activity, as compared to mdx mice. Moreover, BM transplantation experiments demonstrated that the phenotype observed was primarily dependent on lack of PKCθ expression in hematopoietic cells.These results demonstrate a hitherto unrecognized role of immune-cell intrinsic PKCθ activity in the development of DMD. Although the immune cell population(s involved remain unidentified, our findings reveal that PKCθ can be proposed as a new pharmacological target to counteract the disease, as well as to improve the efficacy of gene- or cell- therapy approaches.

  18. Pharmacologic Management of Duchenne Muscular Dystrophy: Target Identification and Preclinical Trials

    Science.gov (United States)

    Kornegay, Joe N.; Spurney, Christopher F.; Nghiem, Peter P.; Brinkmeyer-Langford, Candice L.; Hoffman, Eric P.; Nagaraju, Kanneboyina

    2014-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked human disorder in which absence of the protein dystrophin causes degeneration of skeletal and cardiac muscle. For the sake of treatment development, over and above definitive genetic and cell-based therapies, there is considerable interest in drugs that target downstream disease mechanisms. Drug candidates have typically been chosen based on the nature of pathologic lesions and presumed underlying mechanisms and then tested in animal models. Mammalian dystrophinopathies have been characterized in mice (mdx mouse) and dogs (golden retriever muscular dystrophy [GRMD]). Despite promising results in the mdx mouse, some therapies have not shown efficacy in DMD. Although the GRMD model offers a higher hurdle for translation, dogs have primarily been used to test genetic and cellular therapies where there is greater risk. Failed translation of animal studies to DMD raises questions about the propriety of methods and models used to identify drug targets and test efficacy of pharmacologic intervention. The mdx mouse and GRMD dog are genetically homologous to DMD but not necessarily analogous. Subcellular species differences are undoubtedly magnified at the whole-body level in clinical trials. This problem is compounded by disparate cultures in clinical trials and preclinical studies, pointing to a need for greater rigor and transparency in animal experiments. Molecular assays such as mRNA arrays and genome-wide association studies allow identification of genetic drug targets more closely tied to disease pathogenesis. Genes in which polymorphisms have been directly linked to DMD disease progression, as with osteopontin, are particularly attractive targets. PMID:24936034

  19. [Combined spinal-epidural anesthesia for cesarean section in a parturient with myotonic dystrophy].

    Science.gov (United States)

    Mori, Kosuke; Mizuno, Ju; Nagaoka, Takehiko; Harashima, Toshiya; Morita, Sigeho

    2010-08-01

    Myotonic dystrophy (MD) is a muscle disorder characterized by progressive muscle wasting and weakness, and is the most common form of muscular dystrophy that begins in adulthood, often after pregnancy. MD might be related to occurrence of malignant hyperthermia. Therefore, the cesarean section is often performed for the parturient with MD. We had an experience of combined spinal-epidural anesthesia for cesarean section in a parturient complicated with MD. A 40-year-old woman had rhabdomyolysis caused by ritodrine at 15-week gestation and was diagnosed as MD by electromyography. Her first baby died due to respiratory failure fourth day after birth. She had hatchet face, slight weakness of her lower extremities, and easy fatigability. Her manual muscle test was 5/5 at upper extremities and 4/5 at lower extremities. She underwent emergency cesarean section for premature rupture of the membrane, weak pain during labor, and obstructed labor at 33-week gestation. We placed an epidural catheter from T12/L1 and punctured arachnoid with 25 G spinal needle. We performed spinal anesthesia using 0.5% hyperbaric bupivacaine 1.5 ml and epidural anesthesia using 2% lidocaine 6 ml. Her anesthetic level reached bilaterally to T7 and operation started 18 minutes after combined spinal-epidural anesthesia. Her baby was born 23 minutes after the anesthesia. As her baby was 1/5 at Apgar score, the baby was tracheally intubated and artificially ventilated. The cesarean section was finished in 33 minutes uneventfully. She had no adverse events and was discharged on the 8th postoperative day. Later her baby was diagnosed as congenital MD by gene analysis. Combined spinal-epidural anesthesia with the amide-typed local anesthetic agents could be useful and safe for cesarean section in the parturient with MD.

  20. Quality of life of patients with Duchenne muscular dystrophy: from adolescence to young men.

    Science.gov (United States)

    Lue, Yi-Jing; Chen, Shun-Sheng; Lu, Yen-Mou

    2017-07-01

    This study investigated quality of life (QOL) in adolescent and young men with Duchenne muscular dystrophy (DMD). Health-related QOL and global QOL were assessed with the Short Form 36 (SF-36) and World Health Organization Quality of Life-BREF (WHOQOL-BREF). Associations between functional status and QOL were assessed. All domains of the SF-36 were below Taiwan norms (effect size: -14.2 to -0.5), especially Physical Function, Role Physical, and Social Function. Three of the four domains of the WHOQOL-BREF were below Taiwan norms (effect size: -2.0 to -0.7). The Physical Function of the SF-36 was moderately correlated with functional status (mobility, basic activities of daily living, and arm function). The Social Function of the SF-36 and Social Relationships of the WHOQOL-BREF were also moderately correlated with functional status (impairment, basic activities of daily living, and arm function). The adolescent and young men with DMD had poor health-related and global QOL. Poor QOL was related to both physical condition and social health. We suggest that rehabilitation programs focus on using assistive devices to facilitate arm function and encouraging participation in social activities to improve the QOL of patients with DMD. Implications for rehabilitation Duchenne muscular dystrophy (DMD) is a progressive muscle weakness disease that not only impacts physical health but also leads to poor quality of life in many domains. A valuable rehabilitation goal for patients with DMD is to encourage participation in social activities. Medical care and educational programs should plan a formal transition processes for patients with DMD from pediatric to adult care to maximum their quality of life. Arm function is associated with many domains of global quality of life, so a key element in improving quality of life may be to improve arm function.

  1. The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression.

    Science.gov (United States)

    Kinnett, Kathi; Noritz, Garey

    2017-06-27

    Duchenne muscular dystrophy (DMD or Duchenne) is a progressive, life-limiting muscle-wasting disease that requires comprehensive, multidisciplinary care. This care, at minimum, should include neuromuscular, respiratory, cardiac, orthopedic, endocrine and rehabilitative interventions that address both the primary and secondary manifestations of the disease. The care needs of patients evolve over the cdourse of the disease and as they transition from childhood into young adulthood. In the past two decades, life expectancy has increased significantly by the use of corticosteroids and enhanced clinical management. Nevertheless, each year, patients with Duchenne muscular dystrophy are admitted to emergency departments and intensive care units where medical expertise thrives, but where expertise in rare diseases, such as Duchenne, may not. Emergency care for patients with Duchenne can be as complex as the disease process itself. While any illness or injury may occur in a person with Duchenne, some acute scenarios are much more common in the context of the disease. Making decisions about the clinical care of a person with Duchenne who presents with an acute illness can be quite difficult - in part, because of the extensive use of corticosteroids, which can lead to adrenal suppression. The life of a person with Duchenne needing emergency care may therefore depend upon the ability of the clinician on duty in the emergency department to recognize and mitigate adrenal suppression resulting from corticosteroid dependence. With this in mind, and drawing from expertise and experience with other steroid-dependent diseases, the 'PJ Nicholoff Steroid Protocol' was developed. The purpose of this protocol is to provide clinicians information regarding the safe management of corticosteroid during emergency situations in patients who may have accompanying adrenal suppression. The protocol explains how to recognize the signs and symptoms of acute adrenal crisis, how to prevent it with

  2. Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk.

    Science.gov (United States)

    Vollrath, D; Feng, W; Duncan, J L; Yasumura, D; D'Cruz, P M; Chappelow, A; Matthes, M T; Kay, M A; LaVail, M M

    2001-10-23

    The Royal College of Surgeons (RCS) rat is a widely studied animal model of retinal degeneration in which the inability of the retinal pigment epithelium (RPE) to phagocytize shed photoreceptor outer segments leads to a progressive loss of rod and cone photoreceptors. We recently used positional cloning to demonstrate that the gene Mertk likely corresponds to the retinal dystrophy (rdy) locus of the RCS rat. In the present study, we sought to determine whether gene transfer of Mertk to a RCS rat retina would result in correction of the RPE phagocytosis defect and preservation of photoreceptors. We used subretinal injection of a recombinant replication-deficient adenovirus encoding rat Mertk to deliver the gene to the eyes of young RCS rats. Electrophysiological assessment of animals 30 days after injection revealed an increased sensitivity of treated eyes to low-intensity light. Histologic and ultrastructural assessment demonstrated substantial sparing of photoreceptors, preservation of outer segment structure, and correction of the RPE phagocytosis defect in areas surrounding the injection site. Our results provide definitive evidence that mutation of Mertk underlies the RCS retinal dystrophy phenotype, and that the phenotype can be corrected by treatment of juvenile animals. To our knowledge, this is the first demonstration of complementation of both a functional cellular defect (phagocytosis) and a photoreceptor degeneration by gene transfer to the RPE. These results, together with the recent discovery of MERTK mutations in individuals with retinitis pigmentosa, emphasize the importance of the RCS rat as a model for gene therapy of diseases that arise from RPE dysfunction.

  3. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation.

    Science.gov (United States)

    Ryu, Dongryeol; Zhang, Hongbo; Ropelle, Eduardo R; Sorrentino, Vincenzo; Mázala, Davi A G; Mouchiroud, Laurent; Marshall, Philip L; Campbell, Matthew D; Ali, Amir Safi; Knowels, Gary M; Bellemin, Stéphanie; Iyer, Shama R; Wang, Xu; Gariani, Karim; Sauve, Anthony A; Cantó, Carles; Conley, Kevin E; Walter, Ludivine; Lovering, Richard M; Chin, Eva R; Jasmin, Bernard J; Marcinek, David J; Menzies, Keir J; Auwerx, Johan

    2016-10-19

    Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and nicotinamide adenine dinucleotide (NAD + ) synthesis, consistent with a potential role for the essential cofactor NAD + in protecting muscle from metabolic and structural degeneration. Furthermore, the skeletal muscle transcriptomes of patients with Duchene's muscular dystrophy (DMD) and other muscle diseases were enriched for various poly[adenosine 5'-diphosphate (ADP)-ribose] polymerases (PARPs) and for nicotinamide N-methyltransferase (NNMT), enzymes that are major consumers of NAD + and are involved in pleiotropic events, including inflammation. In the mdx mouse model of DMD, we observed significant reductions in muscle NAD + levels, concurrent increases in PARP activity, and reduced expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD + biosynthesis. Replenishing NAD + stores with dietary nicotinamide riboside supplementation improved muscle function and heart pathology in mdx and mdx/Utr -/- mice and reversed pathology in Caenorhabditis elegans models of DMD. The effects of NAD + repletion in mdx mice relied on the improvement in mitochondrial function and structural protein expression (α-dystrobrevin and δ-sarcoglycan) and on the reductions in general poly(ADP)-ribosylation, inflammation, and fibrosis. In combination, these studies suggest that the replenishment of NAD + may benefit patients with muscular dystrophies or other neuromuscular degenerative conditions characterized by the PARP/NNMT gene expression signatures. Copyright © 2016, American Association for the Advancement of Science.

  4. Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes.

    Directory of Open Access Journals (Sweden)

    Marika Pane

    Full Text Available The 6 minute walk test has been recently chosen as the primary outcome measure in international multicenter clinical trials in Duchenne muscular dystrophy ambulant patients. The aim of the study was to assess the spectrum of changes at 3 years in the individual measures, their correlation with steroid treatment, age and 6 minute walk test values at baseline. Ninety-six patients from 11 centers were assessed at baseline and 12, 24 and 36 months after baseline using the 6 minute walk test and the North Star Ambulatory Assessment. Three boys (3% lost the ability to perform the 6 minute walk test within 12 months, another 13 between 12 and 24 months (14% and 11 between 24 and 36 months (12%. The 6 minute walk test showed an average overall decline of -15.8 (SD 77.3 m at 12 months, of -58.9 (SD 125.7 m at 24 months and -104.22 (SD 146.2 m at 36 months. The changes were significantly different in the two baseline age groups and according to the baseline 6 minute walk test values (below and above 350 m (p<0.001. The changes were also significantly different according to steroid treatment (p = 0.01. Similar findings were found for the North Star Ambulatory Assessment. These are the first 36 month longitudinal data using the 6 minute walk test and North Star Ambulatory Assessment in Duchenne muscular dystrophy. Our findings will help not only to have a better idea of the progression of the disorder but also provide reference data that can be used to compare with the results of the long term extension studies that are becoming available.

  5. Long term natural history data in ambulant boys with Duchenne muscular dystrophy: 36-month changes.

    Science.gov (United States)

    Pane, Marika; Mazzone, Elena Stacy; Sivo, Serena; Sormani, Maria Pia; Messina, Sonia; D'Amico, Adele; Carlesi, Adelina; Vita, Gianluca; Fanelli, Lavinia; Berardinelli, Angela; Torrente, Yvan; Lanzillotta, Valentina; Viggiano, Emanuela; D Ambrosio, Paola; Cavallaro, Filippo; Frosini, Silvia; Barp, Andrea; Bonfiglio, Serena; Scalise, Roberta; De Sanctis, Roberto; Rolle, Enrica; Graziano, Alessandra; Magri, Francesca; Palermo, Concetta; Rossi, Francesca; Donati, Maria Alice; Sacchini, Michele; Arnoldi, Maria Teresa; Baranello, Giovanni; Mongini, Tiziana; Pini, Antonella; Battini, Roberta; Pegoraro, Elena; Previtali, Stefano; Bruno, Claudio; Politano, Luisa; Comi, Giacomo P; Bertini, Enrico; Mercuri, Eugenio

    2014-01-01

    The 6 minute walk test has been recently chosen as the primary outcome measure in international multicenter clinical trials in Duchenne muscular dystrophy ambulant patients. The aim of the study was to assess the spectrum of changes at 3 years in the individual measures, their correlation with steroid treatment, age and 6 minute walk test values at baseline. Ninety-six patients from 11 centers were assessed at baseline and 12, 24 and 36 months after baseline using the 6 minute walk test and the North Star Ambulatory Assessment. Three boys (3%) lost the ability to perform the 6 minute walk test within 12 months, another 13 between 12 and 24 months (14%) and 11 between 24 and 36 months (12%). The 6 minute walk test showed an average overall decline of -15.8 (SD 77.3) m at 12 months, of -58.9 (SD 125.7) m at 24 months and -104.22 (SD 146.2) m at 36 months. The changes were significantly different in the two baseline age groups and according to the baseline 6 minute walk test values (below and above 350 m) (p<0.001). The changes were also significantly different according to steroid treatment (p = 0.01). Similar findings were found for the North Star Ambulatory Assessment. These are the first 36 month longitudinal data using the 6 minute walk test and North Star Ambulatory Assessment in Duchenne muscular dystrophy. Our findings will help not only to have a better idea of the progression of the disorder but also provide reference data that can be used to compare with the results of the long term extension studies that are becoming available.

  6. Altered myofilament structure and function in dogs with Duchenne muscular dystrophy cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ait Mou, Younss; Lacampagne, Alain; Irving, Thomas; Scheuermann, Valérie; Blot, Stéphane; Ghaleh, Bijan; de Tombe, Pieter P.; Cazorla, Olivier

    2018-01-01

    Aim Duchenne Muscular Dystrophy (DMD) is associated with progressive depressed left ventricular (LV) function. However, DMD effects on myofilament structure and function are poorly understood. Golden Retriever Muscular Dystrophy (GRMD) is a dog model of DMD recapitulating the human form of DMD. Objective The objective of this study is to evaluate myofilament structure and function alterations in GRMD model with spontaneous cardiac failure. Methods and results We have employed synchrotron X-rays diffraction to evaluate myofilament lattice spacing at various sarcomere lengths (SL) on permeabilized LV myocardium. We found a negative correlation between SL and lattice spacing in both sub-epicardium (EPI) and sub-endocardium (ENDO) LV layers in control dog hearts. In the ENDO of GRMD hearts this correlation is steeper due to higher lattice spacing at short SL (1.9 μm). Furthermore, cross-bridge cycling indexed by the kinetics of tension redevelopment (ktr) was faster in ENDO GRMD myofilaments at short SL. We measured post-translational modifications of key regulatory contractile proteins. S-glutathionylation of cardiac Myosin Binding Protein-C (cMyBP-C) was unchanged and PKA dependent phosphorylation of the cMyBP-C was significantly reduced in GRMD ENDO tissue and more modestly in EPI tissue. Conclusions We found a gradient of contractility in control dogs' myocardium that spreads across the LV wall, negatively correlated with myofilament lattice spacing. Chronic stress induced by dystrophin deficiency leads to heart failure that is tightly associated with regional structural changes indexed by increased myofilament lattice spacing, reduced phosphorylation of regulatory proteins and altered myofilament contractile properties in GRMD dogs.

  7. Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Siemionow, Maria; Cwykiel, Joanna; Heydemann, Ahlke; Garcia, Jesus; Marchese, Enza; Siemionow, Krzysztof; Szilagyi, Erzsebet

    2018-06-01

    Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD. We introduce two Dystrophin Expressing Chimeric (DEC) cell lines created by ex vivo fusion of human myoblasts (MB) derived from two normal donors (MB N1 /MB N2 ), and normal and DMD donors (MB N /MB DMD ). The efficacy of fusion was confirmed by flow cytometry and confocal microscopy based on donor cell fluorescent labeling (PKH26/PKH67). In vitro, DEC displayed phenotype and genotype of donor parent cells, expressed dystrophin, and maintained proliferation and myogenic differentiation. In vivo, local delivery of both DEC lines (0.5 × 10 6 ) restored dystrophin expression (17.27%±8.05-MB N1 /MB N2 and 23.79%±3.82-MB N /MB DMD ) which correlated with significant improvement of muscle force, contraction and tolerance to fatigue at 90 days after DEC transplant to the gastrocnemius muscles (GM) of dystrophin-deficient mdx/scid mice. This study establishes DEC as a potential therapy for DMD and other types of muscular dystrophies.

  8. Anti-fibrotic effect of pirfenidone in muscle derived-fibroblasts from Duchenne muscular dystrophy patients.

    Science.gov (United States)

    Zanotti, Simona; Bragato, Cinzia; Zucchella, Andrea; Maggi, Lorenzo; Mantegazza, Renato; Morandi, Lucia; Mora, Marina

    2016-01-15

    Tissue fibrosis, characterized by excessive deposition of extracellular matrix proteins, is the end point of diseases affecting the kidney, bladder, liver, lung, gut, skin, heart and muscle. In Duchenne muscular dystrophy (DMD), connective fibrotic tissue progressively substitutes muscle fibers. So far no specific pharmacological treatment is available for muscle fibrosis. Among promising anti-fibrotic molecules, pirfenidone has shown anti-fibrotic and anti-inflammatory activity in animal and cell models, and has already been employed in clinical trials. Therefore we tested pirfenidone anti-fibrotic properties in an in vitro model of muscle fibrosis. We evaluated effect of pirfenidone on fibroblasts isolated from DMD muscle biopsies. These cells have been previously characterized as having a pro-fibrotic phenotype. We tested cell proliferation and migration, secretion of soluble collagens, intracellular levels of collagen type I and fibronectin, and diameter of 3D fibrotic nodules. We found that pirfenidone significantly reduced proliferation and cell migration of control and DMD muscle-derived fibroblasts, decreased extracellular secretion of soluble collagens by control and DMD fibroblasts, as well as levels of collagen type I and fibronectin, and, in DMD fibroblasts only, reduced synthesis and deposition of intracellular collagen. Furthermore, pirfenidone was able to reduce the diameter of fibrotic-nodules in our 3D model of in vitro fibrosis. These pre-clinical results indicate that pirfenidone has potential anti-fibrotic effects also in skeletal muscle fibrosis, urging further studies in in vivo animal models of muscular dystrophy in order to translate the drug into the treatment of muscle fibrosis in DMD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Scan analysis in myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Ell, P J [Landesunfallkrankenhaus, Feldkirch (Austria). Inst. fuer Strahlenmedizin

    1976-08-01

    Myocardial scans with sup(99m)Tc-labelled phosphates are reported to be useful in the diagnosis of acute myocardial infarction. A retrospective survey of 205 patients referred for sup(99m)Tc-phophate bone scanning and with no evidence of recent heart disease revealed an occurrence of 10% of false positive images, that is to say, uptake of phosphate in non-infarcted mayocardium. These striking findings stress the need for critical assessment of the usefulness of this diagnostic technique.

  10. Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism.

    Science.gov (United States)

    Al-Khalidi, Rasha; Panicucci, Chiara; Cox, Paul; Chira, Natalia; Róg, Justyna; Young, Christopher N J; McGeehan, Rhiannon E; Ambati, Kameshwari; Ambati, Jayakrishna; Zabłocki, Krzysztof; Gazzerro, Elisabetta; Arkle, Stephen; Bruno, Claudio; Górecki, Dariusz C

    2018-04-11

    Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder that causes severe disability and death of young men. This disease is characterized by progressive muscle degeneration aggravated by sterile inflammation and is also associated with cognitive impairment and low bone density. Given that no current treatment can improve the long-term outcome, approaches with a strong translational potential are urgently needed. Duchenne muscular dystrophy (DMD) alters P2RX7 signaling in both muscle and inflammatory cells and inhibition of this receptor resulted in a significant attenuation of muscle and non-muscle symptoms in DMD mdx mouse model. As P2RX7 is an attractive target in a range of human diseases, specific antagonists have been developed. Yet, these will require lengthy safety testing in the pediatric population of Duchenne muscular dystrophy (DMD) patients. In contrast, Nucleoside Reverse Transcriptase Inhibitors (NRTIs) can act as P2RX7 antagonists and are drugs with an established safety record, including in children. We demonstrate here that AZT (Zidovudine) inhibits P2RX7 functions acting via the same allosteric site as other antagonists. Moreover, short-term AZT treatment at the peak of disease in DMD mdx mice attenuated the phenotype without any detectable side effects. Recovery was evident in the key parameters such as reduced sarcolemma permeability confirmed by lower serum creatine kinase levels and IgG influx into myofibres, decreased inflammatory cell numbers and inflammation markers in leg and heart muscles of treated mice. Moreover, this short-term therapy had some positive impact on muscle strength in vivo and no detrimental effect on mitochondria, which is the main side-effect of Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Given these results, we postulate that AZT could be quickly re-purposed for the treatment of this highly debilitating and lethal disease. This approach is not constrained by causative DMD mutations and

  11. Myocardial scintigraphy: methods and indications

    International Nuclear Information System (INIS)

    Knapp, W.H.

    1993-01-01

    Myocardial scintigraphy comprises perfusion imaging using TI-201 or - more recently - Tc-99m-labeled compounds with high affinity to myocytes. Imaging with these agents has become an important procedure in the detection of coronary artery disease, particularly in patients with non-diagnostic stress-ECG, in the functional evaluation of coronary stenoses after angiographical documentation in order to meet the adequate therapy decision, in therapy monitoring and follow-up, in the post infarction assessment of myocardial viability and differentiation between severe ischemia and scar and, occasionally, in acute ischemia. The use of positron emitters does not offer significant advantages for mere perfusion imaging, but is indispensable for the scintigraphic investigation of certain aspects of myocardial metabolism, particularly for the differentiation of viable ischemic wall segments from irreversibly damaged tissue. Imaging of myocardial necrosis has been improved by the introduction of labeled antimyosin antibody fragments and offers a considerable clinical potential in the diagnosis of myocarditis and cardiac transplant rejection. Neurohumoral aspects are increasingly involved in our understanding of myocardial failure. Scintigraphy of innervation/neurotransmission contributes to the investigation of pathophysiological alterations in myocardial insufficiency and in heart transplants. (orig.) [de

  12. Why short stature is beneficial in Duchenne muscular dystrophy.

    Science.gov (United States)

    Bodor, Marko; McDonald, Craig M

    2013-09-01

    Duchenne muscular dystrophy (DMD) is caused by a genetic defect resulting in absent dystrophin, yet children are able to walk when small and young but lose this ability as they grow. The mdx mouse has absent dystrophin yet does not exhibit significant disability. Allometric modeling of linearly increasing load per muscle fiber and stress on the sarcolemma with growth and exponential decline associated with loss of muscle fibers correlated with case studies and animal models of DMD. Smaller species or breeds are predictably less affected than large as follows: mdx mice muscular dystrophy (GRMD) dogs < large GRMD dogs < humans. Case reports of combined growth hormone and dystrophin deficiency show a relatively benign course of disease. Future therapeutic trials in DMD might include specific growth inhibitors in combination with standard of care treatments to delay the clinical onset and reduce the severity of disease and disability. Copyright © 2013 Wiley Periodicals, Inc.

  13. Dystrophin Immunity in Duchenne’s Muscular Dystrophy

    Science.gov (United States)

    Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao; Samulski, Jade; McPhee, Scott W.; Samulski, R. Jude; Walker, Christopher M.

    2010-01-01

    SUMMARY We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.) PMID:20925545

  14. The erythrocyte membrane in human muscular dystrophy

    NARCIS (Netherlands)

    W. Ruitenbeek (Willem)

    1979-01-01

    textabstractMore than 250 different forms of human neuromuscular diseases are known. They differ in age of onset, severity of weakness, rate of progression, type of inheritance, groups of muscles affected, frequency of incidence. Sometimes the clinical symptoms are not restricted to nervous

  15. NAD+ Biosynthesis Ameliorates a Zebrafish Model of Muscular Dystrophy

    Science.gov (United States)

    Goody, Michelle F.; Kelly, Meghan W.; Reynolds, Christine J.; Khalil, Andre; Crawford, Bryan D.; Henry, Clarissa A.

    2012-01-01

    Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex– or integrin alpha7–deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction with integrin

  16. NAD+ biosynthesis ameliorates a zebrafish model of muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Michelle F Goody

    Full Text Available Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex- or integrin alpha7-deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction

  17. A bedside measure of body composition in Duchenne muscular dystrophy.

    Science.gov (United States)

    Elliott, Sarah A; Davidson, Zoe E; Davies, Peter S W; Truby, Helen

    2015-01-01

    In clinical practice, monitoring body composition is a critical component of nutritional assessment and weight management in boys with Duchenne muscular dystrophy. We aimed to evaluate the accuracy of a simple bedside measurement tool for body composition, namely bioelectrical impedance analysis, in boys with Duchenne muscular dystrophy. Measures of fat-free mass were determined using a bioelectrical impedance analysis machine and compared against estimations obtained from a reference body composition model. Additionally, the use of raw impedance values was analyzed using three existing predictive equations for the estimation of fat-free mass. Accuracy of bioelectrical impedance analysis was assessed by comparison against the reference model by calculation of biases and limits of agreement. Body composition was measured in 10 boys with Duchenne muscular dystrophy, mean age 9.01 ± 2.34 years. The bioelectrical impedance analysis machine values of fat-free mass were on average 2.3 ± 14.1 kg higher than reference values. Limits of agreement (based on 95% confidence interval of the mean) were -7.4 to 2.9 kg. There was a significant correlation between the mean fat-free mass and difference in fat-free mass between the bioelectrical impedance analysis machine and the reference model (r = -0.86; P = 0.02) suggesting that the bias was not consistent across the range of measurements. The most accurate predictive equation for the estimation of fat-free mass using raw impedance values was the equation by Pietrobelli et al. (mean difference, -0.7 kg; 95% limits of agreement, -3.5 to 2.0 kg). In a clinical setting, where a rapid assessment of body composition is advantageous, the use of raw impedance values, combined with the equation by Pietrobelli et al., is recommended for the accurate estimation of fat-free mass, in boys with Duchenne muscular dystrophy. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Sarcopenia and sarcopenic obesity in patients with muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Luciano eMerlini

    2014-10-01

    Full Text Available Aging sarcopenia and muscular dystrophy are two conditions characterized by lower skeletal muscle quantity, lower muscle strength, and lower physical performance. Aging is associated with a peculiar alteration in body composition called sarcopenic obesity characterized by a decrease in lean body mass and increase in fat mass. To evaluate the presence of sarcopenia and obesity in a cohort of adult patients with muscular dystrophy we have used the measurement techniques considered golden standard for sarcopenia that is for muscle mass dual energy X-ray absorptiometry (DXA, for muscle strength hand held dynamometry, and for physical performance gait speed. The study involved 14 adult patients with different types of muscular dystrophy. We were able to demonstrate that all patient were sarcopenic-obese. We showed in fact that all were sarcopenic based on appendicular lean, fat & bone free, mass index (ALMI. In addition all resulted obese according to the % of body fat determined by DXA in contrast with their body mass index ranging from underweight to obese. Skeletal muscle mass determined by DXA was markedly reduced in all patients and correlated with residual muscle strength determined by hand held dynamometry, and physical performances determined by gait speed and respiratory function. Finally we showed that ALMI was the best linear explicator of muscle strength and physical function. Altogether, our study suggest the relevance of a proper evaluation of body composition in muscular dystrophy and we propose to use, both in research and practice, the measurement techniques that has already been demonstrated effective in aging sarcopenia.

  19. Dystrophin Immunity in Duchenne’s Muscular Dystrophy

    OpenAIRE

    Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao

    2010-01-01

    We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from th...

  20. Duchenne muscular dystrophy with associated growth hormone deficiency

    International Nuclear Information System (INIS)

    Ghafoor, T.; Mahmood, A.; Shams, S.

    2003-01-01

    A patient with duchenne muscular dystrophy (DMD) and growth hormone (GH) deficiency is described who had no clinical evidence of muscular weakness before initiation of GH replacement therapy. Treatment with human GH resulted in appearance of symptoms of easy fatigability and muscle weakness. Thorough investigations including serum creating phosphokinase (CK) levels in recommended in every patient with GH deficiency before starting GH replacement therapy. (author)

  1. CINRG: Infrastructure for Clinical Trials in Duchenne Dystrophy

    Science.gov (United States)

    2012-09-01

    Cardiac Outcome Measures in Children with Muscular Dystrophy o Cardiac MRI Protocol: PITT0110 - Cardiac Magnetic Resonance: A Parallel Protocol...permitted during the study. Study drug. The study drug was PTX (Trental; Sanofi- Aventis U.S. LLC, Bridgewater, NJ) tablets , an FDA-approved pharmaceutical...that is available for oral administration as 400-mg oblong tablets . Both the study drug PTX and placebo were overencapsulated by Capsugel (Pfizer Inc

  2. Disease impact in chronic progressive external ophthalmoplegia: more than meets the eye

    NARCIS (Netherlands)

    Smits, B.W.; Fermont, J.; Delnooz, C.C.S.; Kalkman, J.S.; Bleijenberg, G.; Engelen, B.G.M. van

    2011-01-01

    We determined the extent of disease impact in 28 patients with genetically confirmed chronic progressive external ophthalmoplegia (CPEO) and compared the outcomes to those of matched myotonic dystrophy type I patients. CPEO patients reported a high frequency of severe fatigue (67.9%), pain (96.2%),

  3. Modulation of Stem Cell Differentiation and Myostatin as an Approach to Counteract Fibrosis in Muscle Dystrophy and Regeneration after Injury

    Science.gov (United States)

    2011-03-01

    Duchenne muscular dystrophy (DMD). To examine whether counteracting myostatin, a negative regulator of muscle mass and a pro-lipofibrotic factor...extracellular matrix, and fat, characterizes muscle dystrophy , and in particular Duchenne muscular dystrophy (DMD) (1,2), as seen also in its animal model...stem cells (MDSC) into myogenic as opposed to lipofibrogenic lineages is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD). To

  4. Skeletal muscle CT of lower extremities in myotonic dystrophy

    International Nuclear Information System (INIS)

    Takahashi, Ryosuke; Imai, Terukuni; Sadashima, Hiromichi; Matsumoto, Sadayuki; Yamamoto, Toru; Kusaka, Hirofumi; Yamasaki, Masahiro; Maya, Kiyomi; Tanabe, Masaya

    1988-01-01

    We evaluated the leg and thigh muscles of 4 control subjects and 10 patients with myotonic dystrophy using computed tomography. Taking previous reports about the skeletal muscle CT of myotonic dystrophy into account, we concluded that the following 5 features are characteristic of myotonic dystrophy: 1. The main change is the appearance of low-density areas in muscles; these areas reflect fat tissue. In addition, the muscle mass decreases in size. 2. The leg is more severely affected than the thigh. 3. In the thigh, although the m. quadriceps femoris, especially the vastus muscles, tends to be affected, the m. adductor longus and magnus tend to be preserved. 4. In the leg, although the m. tibialis anterior and m. triceps surae tend to be affected, the m. peroneus longus, brevis, and m. tibialis posterior tend to be preserved. 5. Compensatory hypertrophy is often observed in the m. rectus femoris, m. adductor longus, m. adductor magnus, m. peroneus longus, and m. peroneus brevis, accompanied by the involvement of their agonist muscles. (author)

  5. [New international classification of corneal dystrophies and clinical landmarks].

    Science.gov (United States)

    Lisch, W; Seitz, B

    2008-07-01

    The International Committee on Classification of Corneal Dystrophies, briefly IC (3)D, was founded with the sponsorship of the American Cornea Society and the American Academy of Ophthalmology in July 2005. This committee consists of 17 corneal experts (1) from USA, Asia and Europe. The goal of this group was to develop a new, internationally accepted classification of corneal dystrophies (CD) based on modern clinical, histological and genetical knowledge. The aim of the new classification should be to avoid wrong interpretations and misnomers of the different forms of CD. The IC (3)D extensive manuscript is in press as Supplement publication in the journal "Cornea". The 25 different CD are divided in four categories by clinical and genetical knowledge. Additionally, templates for each type of CD are included. Finally, many typical color slit-lamp photos are presented in the publication together with essential references and current genetical results in tabular form. As members of IC (3)D the authors present a clinical landmark survey of the different corneal dystrophies. The ophthalmologist is the first to examine and to diagnose a new patient with a probable CD at the slit-lamp. Our elaborated table of landmarks is supposed to be a "bridge" for the ophthalmologist to precisely define the corneal opacities of a presumed CD. This "bridge" makes it easier for them to study the IC (3)D Supplement publication and to get more information including adequate differential diagnosis.

  6. Heme oxygenase and carbon monoxide protect from muscle dystrophy.

    Science.gov (United States)

    Chan, Mun Chun; Ziegler, Olivia; Liu, Laura; Rowe, Glenn C; Das, Saumya; Otterbein, Leo E; Arany, Zoltan

    2016-11-28

    Duchenne muscle dystrophy (DMD) is one of the most common lethal genetic diseases of children worldwide and is 100% fatal. Steroids, the only therapy currently available, are marred by poor efficacy and a high side-effect profile. New therapeutic approaches are urgently needed. Here, we leverage PGC-1α, a powerful transcriptional coactivator known to protect against dystrophy in the mdx murine model of DMD, to search for novel mechanisms of protection against dystrophy. We identify heme oxygenase-1 (HO-1) as a potential novel target for the treatment of DMD. Expression of HO-1 is blunted in the muscles from the mdx murine model of DMD, and further reduction of HO-1 by genetic haploinsufficiency worsens muscle damage in mdx mice. Conversely, induction of HO-1 pharmacologically protects against muscle damage. Mechanistically, HO-1 degrades heme into biliverdin, releasing in the process ferrous iron and carbon monoxide (CO). We show that exposure to a safe low dose of CO protects against muscle damage in mdx mice, as does pharmacological treatment with CO-releasing molecules. These data identify HO-1 and CO as novel therapeutic agents for the treatment of DMD. Safety profiles and clinical testing of inhaled CO already exist, underscoring the translational potential of these observations.

  7. Prenatal molecular diagnosis of inherited neuromuscular diseases: Duchenne/Becker muscular dystrophy, myotonic dystrophy type 1 and spinal muscular atrophy.

    Science.gov (United States)

    Esposito, Gabriella; Ruggiero, Raffaella; Savarese, Maria; Savarese, Giovanni; Tremolaterra, Maria Roberta; Salvatore, Francesco; Carsana, Antonella

    2013-12-01

    Neuromuscular disease is a broad term that encompasses many diseases that either directly, via an intrinsic muscle disorder, or indirectly, via a nerve disorder, impairs muscle function. Here we report the experience of our group in the counselling and molecular prenatal diagnosis of three inherited neuromuscular diseases, i.e., Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), spinal muscular atrophy (SMA). We performed a total of 83 DMD/BMD, 15 DM1 and 54 SMA prenatal diagnoses using a combination of technologies for either direct or linkage diagnosis. We identified 16, 5 and 10 affected foetuses, respectively. The improvement of analytical procedures in recent years has increased the mutation detection rate and reduced the analytical time. Due to the complexity of the experimental procedures and the high, specific professional expertise required for both laboratory activities and the related counselling, these types of analyses should be preferentially performed in reference molecular diagnostic centres.

  8. Cardiac involvement in patients with Becker muscular dystrophy: new diagnostic and pathophysiological insights by a CMR approach

    Directory of Open Access Journals (Sweden)

    Thiene Gaetano

    2008-11-01

    Full Text Available Abstract Background Becker-Kiener muscular dystrophy (BMD represents an X-linked genetic disease associated with myocardial involvement potentially resulting in dilated cardiomyopathy (DCM. Early diagnosis of cardiac involvement may permit earlier institution of heart failure treatment and extend life span in these patients. Both echocardiography and nuclear imaging methods are capable of detecting later stages of cardiac involvement characterised by wall motion abnormalities. Cardiovascular magnetic resonance (CMR has the potential to detect cardiac involvement by depicting early scar formation that may appear before onset of wall motion abnormalities. Methods In a prospective two-center-study, 15 male patients with BMD (median age 37 years; range 11 years to 56 years underwent comprehensive neurological and cardiac evaluations including physical examination, echocardiography and CMR. A 16-segment model was applied for evaluation of regional wall motion abnormalities (rWMA. The CMR study included late gadolinium enhancement (LGE imaging with quantification of myocardial damage. Results Abnormal echocardiographic results were found in eight of 15 (53.3% patients with all of them demonstrating reduced left ventricular ejection fraction (LVEF and rWMA. CMR revealed abnormal findings in 12 of 15 (80.0% patients (p = 0.04 with 10 (66.6% having reduced LVEF (p = 0.16 and 9 (64.3% demonstrating rWMA (p = 0.38. Myocardial damage as assessed by LGE-imaging was detected in 11 of 15 (73.3% patients with a median myocardial damage extent of 13.0% (range 0 to 38.0%, an age-related increase and a typical subepicardial distribution pattern in the inferolateral wall. Ten patients (66.7% were in need of medical heart failure therapy based on CMR results. However, only 4 patients (26.7% were already taking medication based on clinical criteria (p = 0.009. Conclusion Cardiac involvement in patients with BMD is underdiagnosed by echocardiographic methods resulting

  9. Modulation of Stem Cells Differentiation and Myostatin as an approach to Counteract fibrosis in Muscle Dystrophy and Regeneration after Injury

    Science.gov (United States)

    2010-03-01

    Duchenne muscular dystrophy (DMD), hampers cell therapy in the muscle , and is a feasible therapeutic target. Myostatin (Mst), a...17 Figure 18 Figure 19 Figure 20 Figure 21 • Muscle lipofibrotic degeneration characterizes Duchenne muscular dystrophy (DMD), hampers cell therapy...SUBJECT TERMS Myostatin, muscle dystrophy , stem cells, myogenesis, Oct-4; Duchenne 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT

  10. Patients with Duchenne muscular dystrophy are significantly shorter than those with Becker muscular dystrophy, with the higher incidence of short stature in Dp71 mutated subgroup.

    Science.gov (United States)

    Matsumoto, Masaaki; Awano, Hiroyuki; Lee, Tomoko; Takeshima, Yasuhiro; Matsuo, Masafumi; Iijima, Kazumoto

    2017-11-01

    Duchenne and Becker muscular dystrophy (DMD/BMD) are caused by mutations in the dystrophin gene and are characterized by severe and mild progressive muscle wasting, respectively. Short stature has been reported as a feature of DMD in the Western hemisphere, but not yet confirmed in Orientals. Height of young BMD has not been fully characterized. Here, height of ambulant and steroid naive Japanese 179 DMD and 42 BMD patients between 4 and 10 years of age was retrospectively examined using height standard deviation score (SDS). The mean height SDS of DMD was -1.08 SD that was significantly smaller than normal (p < 0.001), indicating short stature of Japanese DMD. Furthermore, the mean height SDS of BMD was -0.27 SD, suggesting shorter stature than normal. Remarkably, the mean height SDS of DMD was significantly smaller than that of BMD (p < 0.0001). In DMD higher incidence of short stature (height SDS < -2.5 SD) was observed in Dp71 subgroup having mutations in dystrophin exons 63-79 than others having mutations in exons 1-62 (27.8% vs. 7.5%, p = 0.017). These suggested that height is influenced by dystrophin in not only DMD but also BMD and that dystrophin Dp71 has a role in height regulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Acute Myocardial Infarction Patients

    Directory of Open Access Journals (Sweden)

    Bruce Ovbiagele

    2011-01-01

    Full Text Available Background. Diabetes mellitus (DM confers high vascular risk and is a growing national epidemic. We assessed clinical characteristics and prevalence of diagnosed DM among patients hospitalized with acute myocardial infarction (AMI in the US over the last decade. Methods. Data were obtained from all states within the US that contributed to the Nationwide Inpatient Sample. All patients admitted to hospitals between 1997 and 2006 with a primary discharge diagnosis of AMI were included. Time trends in the proportion of these patients with DM diagnosis were computed. Results. The portion of patients with comorbid diabetes among AMI hospitalizations increased substantially from 18% in 1997 to 30% in 2006 (<.0001. Absolute numbers of AMI hospitalizations in the US decreased 8% (from 729, 412 to 672, 243, while absolute numbers of AMI hospitalizations with coexisting DM rose 51% ((131, 189 to 198, 044, both (<.0001. Women with AMI were significantly more likely to have DM than similarly aged men, but these differences diminished with increasing age. Conclusion. Although overall hospitalizations for AMI in the US diminished over the last decade, prevalence of diabetes rose substantially. This may have important consequences for the future societal vascular disease burden.

  12. Early spontaneous intermittent myocardial reperfusion during acute myocardial infarction is associated with augmented thrombogenic activity and less myocardial damage

    NARCIS (Netherlands)

    Haider, A.W.; Andreotti, F.; Hackett, D.R.; Tousoulis, D.; Kluft, C.; Maseri, A.; Davies, G.J.

    1995-01-01

    Objectives. This study investigated the influence of early spontaneous intermittent reperfusion on the extent of myocardial damage and its relation to endogenous hemostatic activity, Background. In the early phase of acute myocardial infarction coronary occlusion is often intermittent, even before

  13. Alterations in Notch signalling in skeletal muscles from mdx and dko dystrophic mice and patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Church, Jarrod E; Trieu, Jennifer; Chee, Annabel; Naim, Timur; Gehrig, Stefan M; Lamon, Séverine; Angelini, Corrado; Russell, Aaron P; Lynch, Gordon S

    2014-04-01

    New Findings What is the central question of this study? The Notch signalling pathway plays an important role in muscle regeneration, and activation of the pathway has been shown to enhance muscle regeneration in aged mice. It is unknown whether Notch activation will have a similarly beneficial effect on muscle regeneration in the context of Duchenne muscular dystrophy (DMD). What is the main finding and its importance? Although expression of Notch signalling components is altered in both mouse models of DMD and in human DMD patients, activation of the Notch signalling pathway does not confer any functional benefit on muscles from dystrophic mice, suggesting that other signalling pathways may be more fruitful targets for manipulation in treating DMD. Abstract In Duchenne muscular dystrophy (DMD), muscle damage and impaired regeneration lead to progressive muscle wasting, weakness and premature death. The Notch signalling pathway represents a central regulator of gene expression and is critical for cellular proliferation, differentiation and apoptotic signalling during all stages of embryonic muscle development. Notch activation improves muscle regeneration in aged mice, but its potential to restore regeneration and function in muscular dystrophy is unknown. We performed a comprehensive examination of several genes involved in Notch signalling in muscles from dystrophin-deficient mdx and dko (utrophin- and dystrophin-null) mice and DMD patients. A reduction of Notch1 and Hes1 mRNA in tibialis anterior muscles of dko mice and quadriceps muscles of DMD patients and a reduction of Hes1 mRNA in the diaphragm of the mdx mice were observed, with other targets being inconsistent across species. Activation and inhibition of Notch signalling, followed by measures of muscle regeneration and function, were performed in the mouse models of DMD. Notch activation had no effect on functional regeneration in C57BL/10, mdx or dko mice. Notch inhibition significantly depressed the

  14. In vivo study of myocardial elastography under graded ischemia conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Wei-Ning; Provost, Jean; Konofagou, Elisa E [Department of Biomedical Engineering, Columbia University, New York, NY (United States); Fujikura, Kana [Department of Radiology, Columbia University, New York, NY (United States); Wang Jie, E-mail: ek2191@columbia.edu [Department of Medicine, Columbia University, New York, NY (United States)

    2011-02-21

    The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction

  15. Targeting early PKCθ-dependent T-cell infiltration of dystrophic muscle reduces disease severity in a mouse model of muscular dystrophy.

    Science.gov (United States)

    Lozanoska-Ochser, Biliana; Benedetti, Anna; Rizzo, Giuseppe; Marrocco, Valeria; Di Maggio, Rosanna; Fiore, Piera; Bouche, Marina

    2018-03-01

    Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy and contributes to muscle fibre injury and disease progression. Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate mdx mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis. Based on our comprehensive analysis of the kinetics of the immune response, we further identify the early pre-necrotic stage of muscular dystrophy as the relevant time frame for T-cell-based interventions. We focused on protein kinase C θ (PKCθ, encoded by Prkcq), a critical regulator of effector T-cell activation, as a potential target to inhibit T-cell activity in dystrophic muscle. Lack of PKCθ not only reduced the frequency and number of infiltrating T cells but also led to quantitative and qualitative changes in the innate immune cell infiltrate in mdx/Prkcq -/- muscle. These changes were due to the inhibition of T cells, since PKCθ was necessary for T-cell but not for myeloid cell infiltration of acutely injured muscle. Targeting T cells with a PKCθ inhibitor early in the disease process markedly diminished the size of the inflammatory cell infiltrate and resulted in reduced muscle damage. Moreover, diaphragm necrosis and fibrosis were also reduced following treatment. Overall, our findings identify the early T-cell infiltrate as a therapeutic target and highlight the potential of PKCθ inhibition as a therapeutic approach to muscular dystrophy. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Association of myocardial cell necrosis with experimental cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Revis, N W; Cameron, A J.V.

    1979-01-01

    Cardiac hypertrophy was induced in rabbits by injecting thyroxime or isoprenaline, or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the ratios of bound to free forms of five lysosomal enzymes, a change in serum creatine phosphokinase and lactate dehydrogenase, and a change in the morphology of the myocardial cells. Isoprenaline treatment for 5 days induced a maximal change in heart weight, in the ratio of lysosomal enzymes, and in the serum enzymes. Thyroxine treatment was required for 15 days before maximal changes in heart weight, ratio, and serum enzymes were observed. In contrast, coarctation of the aorta caused a progressive change in heart weight, in the ratio of lysosomal enzymes, and in serum enzymes. These results suggest that necrosis of the myocardial cells does indeed accompany cardiac hypertrophy. It was further observed that autophagosomes, degenerating mitochondria in the myocardial cells during the induction of cardiac hypertrophy, and myofibril lysis were found, all of which confirms the suggestion of myocardial cell necrosis in the experimentally enlarged heart.

  17. Clinical study on myocardial imaging with. beta. -methyl-p-( sup 123 I)-iodophenyl-pentadecanoic acid in patients with mitochondrial myopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kihara, Koichi; Nakajo, Masayuki; Shono, Hirohisa (Kagoshima Univ. (Japan). Faculty of Medicine) (and others)

    1992-04-01

    Myocardial imaging with {beta}-methyl-p-({sup 123}I)-iodophenyl-pentadecanoic acid ({sup 123}I-BMIPP), a new radiopharmaceutical designed to evaluate myocardial fatty acid metabolism, was performed in 7 patients with mitochondrial myopathy to detect their myocardial damages in comparison with {sup 201}Tl myocardial imaging. These patients were divided into 4 chronic progressive external ophthalmoplegia (CPEO) cases, 2 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) cases and 1 myoclonus epilepsy with ragged-red fibers (MERRF). In visual assessment, we observed more myocardial segments with decreased uptake of {sup 123}I-BMIPP compared to {sup 201}Tl in MELAS cases than in CPEO cases. The mean myocardial uptake of {sup 123}I-BMIPP was higher than that of {sup 201}Tl in CPEO cases. On the other hand, in MELAS and MERRF cases, the mean myocardial uptake of {sup 123}I-BMIPP was lower than that of {sup 201}Tl. Abnormal findings suggesting myocardial damages were observed in echocardiogram and/or in electrocardiogram in MELAS and MERRF cases, while no such abnormal findings were observed in CPEO cases. Along with the previously reported experimental result that the impairment of rat myocardial mitochondria decreased myocardial uptake of {sup 123}I-BMIPP, these results suggest that {sup 123}I-BMIPP may be useful to detect myocardial damages in patients with mitochondrial myopathy. (author)

  18. Clinical study on myocardial imaging with β-methyl-p-(123I)-iodophenyl-pentadecanoic acid in patients with mitochondrial myopathy

    International Nuclear Information System (INIS)

    Kihara, Koichi; Nakajo, Masayuki; Shono, Hirohisa

    1992-01-01

    Myocardial imaging with β-methyl-p-( 123 I)-iodophenyl-pentadecanoic acid ( 123 I-BMIPP), a new radiopharmaceutical designed to evaluate myocardial fatty acid metabolism, was performed in 7 patients with mitochondrial myopathy to detect their myocardial damages in comparison with 201 Tl myocardial imaging. These patients were divided into 4 chronic progressive external ophthalmoplegia (CPEO) cases, 2 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) cases and 1 myoclonus epilepsy with ragged-red fibers (MERRF). In visual assessment, we observed more myocardial segments with decreased uptake of 123 I-BMIPP compared to 201 Tl in MELAS cases than in CPEO cases. The mean myocardial uptake of 123 I-BMIPP was higher than that of 201 Tl in CPEO cases. On the other hand, in MELAS and MERRF cases, the mean myocardial uptake of 123 I-BMIPP was lower than that of 201 Tl. Abnormal findings suggesting myocardial damages were observed in echocardiogram and/or in electrocardiogram in MELAS and MERRF cases, while no such abnormal findings were observed in CPEO cases. Along with the previously reported experimental result that the impairment of rat myocardial mitochondria decreased myocardial uptake of 123 I-BMIPP, these results suggest that 123 I-BMIPP may be useful to detect myocardial damages in patients with mitochondrial myopathy. (author)

  19. Thallium-201 myocardial imaging in acute-myocardial infarction

    International Nuclear Information System (INIS)

    Wackers, F.J.Th.; Lie, K.I.; Sokole, E.B.; Wellens, H.J.J.; Samson, G.; Schoot, J.B. van der

    1980-01-01

    Thallium-201 scintigraphy has proven to be an early and highly sensitive technique to detect myocardial perfusion abnormalities in patients with acute myocardial infarction. During the early phase of acute myocardial infarction, patients may be hemodynamically and electrically unstable. Therefore, scintigraphy is performed preferably at the bed side in the Coronary Care Unit using a mobile gamma camera. Additionally, in order to shorten imaging time in these often critically ill patients, the authors recommend injecting no less than 2 mCi of 201 Tl. Using this dosage, the imaging time per view will be approximately five minutes. Routinely, three views are taken: the first view is a supine 45 0 left-anterior-oblique view, followed by a supine anterior view and finally a left-lateral view, the latter with the patient turned on the right side. (Auth.)

  20. Myocardial perfusion imaging for detection of silent myocardial ischemia

    International Nuclear Information System (INIS)

    Beller, G.A.

    1988-01-01

    Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging. 11 references