Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DMD”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMed1988

Dystrophin and nebulin in the muscular dystrophies.

Skeletal muscle from patients with 5 different forms of muscular dystrophy and from 6 fetuses at high risk (95%) for Duchenne muscular dystrophy (DMD) were probed with specific antibodies for the presence of dystrophin and nebulin. Dystrophin was absent in all 5 patients with DMD and 4 of 6 fetuses at high risk for DMD and present in trace amounts in the remaining two. Dystrophin was also undetectable in one borderline DMD/Becker muscular dystrophy (BMD) case and reduced in 2 of 4 cases of BMD. In contrast, dystrophin was present in all 16 biopsies from 4 other types of muscular dystrophy (congenital, limb girdle, Emery-Dreifuss and facioscapulohumeral). Nebulin profiles varied with the type, severity and duration of the dystrophic process. Nebulin was present in 5 of 6 DMD fetal samples but vastly reduced or absent in all samples of clinically manifest DMD.

Adolescent↗
PubMed1990

Dystrophin immunostaining in muscles from patients with different types of muscular dystrophy: a Brazilian study.

The localization of the protein dystrophin was studied using the immunofluorescence method, in muscle biopsies from 74 patients affected by different types of muscular dystrophy and 4 normal controls. In 15 patients with limb-girdle muscular dystrophy (LGMD) the pattern was indistinguishable from normal. Among 42 Duchenne patients (DMD), 3 were totally negative and 39 showed a variable proportion (4-30%) of partially labelled fibers. With one exception 17 Becker dystrophy patients (BMD), showed a positive sarcolemmal reaction. A diffuse reaction inside the fibers, which was not observed in normal controls, was seen in the majority of DMD and also in some of the BMD patients. Based on these observations it is suggested that in DMD, a small quantity of protein is still present or there is a cross-reaction with other proteins which share some homology with dystrophin. The present results suggest that it is possible to make a differential diagnosis between DMD and BMD through dystrophin immunohistochemistry. However, to distinguish between patients with BMD and LGMD phenotypes, or DMD and outliers, complementary immunoblot studies and quantitative determination of dystrophin are necessary.

Adolescent↗
PubMed1993

Corticosteroid therapy in Duchenne muscular dystrophy.

In recent years, various clinical trials have documented the benefit of glucocorticoid therapy in the palliation of Duchenne muscular dystrophy (DMD). Prednisone therapy, daily or on alternate days, has been confirmed to be of value in enhancing muscle strength and function in DMD for up to two years. However, there is evidence that corticosteroid treatment results in muscle weakness and degeneration. This review, therefore, examines the available studies and addresses various possible mechanisms involved in the efficacy of prednisone therapy and amelioration of DMD. The progression of DMD is known to be associated with profound changes in structure, biochemistry and physiology of the affected muscles. It is hypothesized, therefore, that these very changes offer a fortunate set of circumstances, and it is owing to these alterations, as well as the well known anti-inflammatory/immunosuppressive action of steroid, that muscles in DMD are rendered responsive resulting in significant improvement of muscle bulk and function.

Adolescent↗
PubMed1984

Electrophysiological effects of desmethylimipramine and desmethyldoxepin on canine cardiac Purkinje fibers.

Although the tricyclic antidepressant drugs imipramine and doxepin exert similar direct electrophysiological effects on cardiac cells, toxic cardiac arrhythmias and conduction disturbances are much more commonly associated with imipramine than doxepin in clinical use. To ascertain if this discrepancy could be due to different cellular electrophysiological actions of active metabolites of imipramine and doxepin, the effects of desmethylimipramine (DMI) and desmethyldoxepin (DMD) on isolated, superfused, canine cardiac Purkinje fibers were studied by glass microelectrodes and programmed stimulation. At a concentration of 50 ng/ml neither DMI nor DMD affected the resting membrane potential (RMP), action potential amplitude (Amp), maximum upstroke velocity of phase 0 (Vmax), action potential duration to repolarization to 50 and 100% of the amplitude (APD50, APD100), effective refractory period (ERP), or conduction velocity (CV). At 250 ng/ml neither drug affected Amp, APD100, or CV; both compounds reduced APD50 by 10 to 15%; and DMD but not DMI caused small reductions of RMP, Vmax, and ERP. At 1000 ng/ml neither DMI nor DMD affected RMP but both caused more marked reductions of APD50 (31 to 35%) and ERP (21 to 23%). At this concentration both substances also reduced Amp by 6 to 7%, Vmax by 28 to 35%, APD100 by 7 to 12%, and CV by 15 to 25%. These effects of DMI and DMD are similar to those produced by the parent drugs. Differences in cardiotoxicity between imipramine and doxepin in clinical use are probably not due to different direct cellular electrophysiological effects of the circulating demethylated metabolites of these drugs.

Action Potentials↗
PubMed1986

A physical map of 4 million bp around the Duchenne muscular dystrophy gene on the human X-chromosome.

Employing pulsed field gradient electrophoresis, we constructed a 4.5 million bp (Mb) Sfil restriction map of the human X-chromosomal region p21, harboring genes for Duchenne (DMD) and Becker Muscular Dystrophy. In a DMD patient with additional chronic granulomatosis and retinitis pigmentosa, the proximal 3.5 Mb is deleted. Another DMD patient, with additional glycerol kinase deficiency and adrenal hypoplasia, lacks at least 3.3 Mb in the middle region, including marker C7 but not B24, placing C7 closer to DMD. Another DMD patient has a partial pERT-87 deletion of minimally 140 kb. Truncated Sfil fragments in a female X:21 translocation patient place the junction probe XJ1.1 115 kb from the distal end of the normal fragment. Probe pERT-84 maps to the same fragment, within 750 kb of XJ1.1.

Chromosome Aberrations↗
PubMed1993

Changes in cytosolic resting ionized calcium level and in calcium transients during in vitro development of normal and Duchenne muscular dystrophy cultured skeletal muscle measured by laser cytofluorimetry using indo-1.

Intracellular calcium activity was recorded during in vitro myogenesis of human normal and DMD muscle, using the calcium probe Indo-1 under laser illumination, at rest and during different kinds of stimulation (acetylcholine, high K+, caffeine). In myoblasts, the resting intracellular calcium level was significantly larger in DMD cells (89 +/- 9 nM; n = 40 vs 37 +/- 5 nM; n = 22) but there was no significant difference in myotubes, after fusion (44 +/- 4 nM; n = 34 vs 36 +/- 4 nM; n = 52). A similar evolution was observed in cells cultured from FSH biopsies. The amplitude of ACh- and high K(+)-induced calcium transients was significantly halved in DMD myotubes as compared to control ones and non-significantly decreased for caffeine responses. Some alterations in the kinetics of responses were observed in DMD muscle: the rising phases of ACh- and high K(+)-elicited transients and the decaying phase of the ACh-responses were significantly slowed down. It is concluded that: (i) in aneurally cultured human muscle, an increase in the basal level of internal calcium can occur at early stages of myogenesis before the expression of the dystrophin gene; and (ii) the changes in calcium transients induced by depolarization or direct stimulation of sarcoplasmic reticulum are not susceptible of inducing a calcium overload in DMD cells.

Acetylcholine↗
PubMed1993

Cost-effectiveness of neonatal screening for Duchenne muscular dystrophy--how does this compare to existing neonatal screening for metabolic disorders?

Costs of screening a series of 18,152 newborn males for Duchenne muscular dystrophy (DMD) in Canada were evaluated. The final aim of neonatal screening for DMD is the avoidance of additional cases in the families identified. Total costs to avoid one case of DMD were estimated at Cdn. $172,000, while the incremental costs were found to be $83,000. Reagent costs, test sensitivity, efficacy of screening and compliance with genetic advice were identified as factors crucial for cost-effectiveness. Costs of neonatal screening for DMD are compared with costs of neonatal screening for inborn metabolic disorders. It is found that the two programmes are similar in costs. Earlier predictions of inordinate costs of screening for DMD are refuted.

Cost-Benefit Analysis↗
PubMed1984

Proposed treatment of Duchenne muscular dystrophy with desferrioxamine.

The primary disturbance in Duchenne muscular dystrophy (DMD) appears to affect membrane function, and changes characteristic of oxidant-induced damage occur in skeletal muscle and erythrocytes. There is recent evidence that DMD is a functional tocopherol deficiency, with reduced levels of the lipoprotein required to carry tocopherol to tissues. This may explain the parallels between DMD and dietary tocopherol deficiency. Thus DMD should follow the usual experience of other examples of oxidative pathology, where the balance between tocopherol, the main antioxidant in membrane lipids, and non protein-bound iron, an important catalyst of reactions which produce oxidizing free radicals, largely determines whether or not tissue damage occurs. Desferrioxamine prevents oxidant damage in vitro and in vivo by removing this iron, and may therefore be able to reverse the muscle damage of DMD. Recent experience with this drug in long term dialysis patients is consistent with this suggestion.

Animals↗
PubMedDate not supplied

Etiology of intellectual impairment in Duchenne muscular dystrophy.

The precise etiology of intellectual impairment in Duchenne muscular dystrophy (DMD) is unknown. Histopathologic and computed tomographic studies have revealed structural brain changes; however, to our knowledge, no cranial magnetic resonance imaging (MRI) studies have been performed on DMD patients to further delineate these structural changes. We prospectively studied 4 DMD patients by cranial MRI, DNA deletion analysis, clinical evaluation, and intelligence testing. There was no significant correlation between verbal intelligence scores and MRI findings, DNA deletion, or the clinical severity of the disease. These first MRI studies of DMD did not reveal any significant anatomic brain alteration, other than mild atrophy in 2 patients. We believe these results must be considered when investigating the etiology of intellectual impairment in DMD in future studies with larger patient samples.

Adolescent↗
PubMedDate not supplied

End of life care in Duchenne muscular dystrophy.

End of life care for patients with Duchenne muscular dystrophy (DMD) has become increasingly complex because of new technologies, changes in medical personnel over periods of time, emergence of home health care systems, and increasing patient and family autonomy in decision-making. In this review, we discuss the medical problems, particularly respiratory and cardiac failure, faced by DMD patients. Current concepts concerning the evaluation and options for treatment of these problems are presented as well as the ethical issues involved in the care of the DMD patient. These issues include the medical indications for treatment, patient preferences, quality-of-life issues, and contextual features related to legal, institutional, religious, geographic, cultural, social, and financial factors. We also present our experience at Loma Linda University Medical Center over the past 10 years in the development of a home mechanical ventilation program for DMD patients and an algorithm for the evaluation of these patients. Many patients with DMD do well on long-term ventilation, but some find that their quality of life is less than desirable and choose to discontinue this method of life-prolongation. Many of these new options are very expensive, making the decision to use them a difficult one. Ultimately, these are societal issues that require clear reflection on matters of resource allocation that should be performed by health care professionals, citizens, and health planners.

Adolescent↗
PubMed1989

Mapping of four translocation breakpoints within the Duchenne muscular dystrophy gene.

There are over 20 females with Duchenne or Becker muscular dystrophy (DMD or BMD) who have X-autosome translocations that break the X chromosome within band Xp21. Several of these translocations have been mapped with genomic probes to regions throughout the large (approximately 2000 kb) DMD gene. In this report, a cDNA clone from the 5' end of the gene was used to further map the breakpoints in four X-autosome translocations. A t(X;21) translocation in a patient with BMD and a t(X;1) translocation in a patient with DMD were found to break within a large 110-kb intron between exons 7 and 8. Two other DMD translocations, t(X;5) and t(X;11), were found to break between the first and the second exon of the gene within a presumably large intron (greater than 100 kb). These results demonstrate that all four translocations have disrupted the DMD gene and make it possible to clone and sequence the breakpoints. This will in turn determine whether these translocations occur by chance in these large introns or whether there are sequences that predispose to translocations.

Chromosome Mapping↗
PubMed1991

Energy status of cells lacking dystrophin: an in vivo/in vitro study of mdx mouse skeletal muscle.

Although great strides have been made in understanding the genetics of Duchenne muscular dystrophy (DMD), uncertainty still remains as to the metabolic changes which are associated with the disease. We have used the recently discovered animal model of DMD, the mdx mouse, to study aspects of high energy phosphate metabolism and metabolic control indices in dystrophic muscle. This model of DMD has the dual advantage of having a genetic defect which is homologous to that in human DMD, and it lacks the fatty infiltration and necrosis which makes biochemical analysis of DMD so difficult. We have used nuclear magnetic resonance spectroscopy (NMR) to monitor developmental changes in high energy phosphates and pH. No differences were observed between young (less than 40-50 days old) control and mdx mice. The pH increase and alterations in phosphate ratios (i.e., a decline in PCr/ATP) observed in adult mdx vs. control mice are qualitatively similar to those observed in humans. Biochemical analysis showed a small decline in ATP and PCr content and a decline in some indices of energy status in adult mdx mice. As young mdx mice appeared to be normal, the lack of dystrophin does not correlate with metabolic changes. The changes which were observed were small enough that alterations in fibre composition could be the major contributory factor.

Adenine Nucleotides↗
PubMed1991

Expression of myosin heavy chain isoforms in Duchenne muscular dystrophy patients and carriers.

The expression of MHC isoforms in the skeletal muscles of nine patients with Duchenne muscular dystrophy (DMD) (from 2.5 to 15 yr of age) and three DMD carriers was studied using different specific anti-MHC MAbs. We also analyzed muscle fiber size and fiber reactivity with acridine orange and/or with a surface antigen marker. One-quarter of all fibers of DMD patients, or less with age, were of normal size and contained only adult slow MHC. Half of the muscle fibers contained adult and developmental MHCs. Only half of these fibers were representative of an active regenerative process. MHC co-expression also altered the proportion of normal fast or slow fibers. Adult fast MHCs were expressed as unique MHC only in small and very small fibers in the oldest DMD patients. In DMD carrier muscles, the greatest alterations in MHC expression were observed in patients with the most reduced dystrophin expression. However, MHC changes in dystrophin-positive fibers were similar to those observed in dystrophin-free fibers. In conclusion, disruptions or delays in the switching of all genes coding for adult fast and slow MHC and developmental MHC coincided with dystrophin deletion and with perturbations in its expression.

Adolescent↗
PubMed1991

Dystrophin immunofluorescence pattern in manifesting and asymptomatic carriers of Duchenne's and Becker muscular dystrophies of different ages.

In order to investigate if the same apparent decrease in dystrophin negative fibers with aging observed in mouse mdx female heterozygotes also occurs in carriers of the DMD and BMD gene, we have studied the muscle of 29 DMD carriers (19 adults and 10 young daughters of obligate carriers, including 3 manifesting carriers) and 5 adult asymptomatic heterozygotes for Becker dystrophy (BMD). All young DMD possible carriers and 11 of 24 adult DMB/BMD heterozygotes had increased serum enzymes activities. A population of dystrophin negative fibers, more evident with the use of the C-terminal antibody, was seen in the three manifesting and in a 9-yr-old possible DMD carrier. In the remaining females, a positive immunohistochemical pattern of dystrophin, which did not differ from normal controls, was observed. Our results suggest that: (1) the increased population of dystrophin negative fibers reported in young mdx female heterozygotes was not seen in young DMD carriers, aged 6-17 yr; and (2) abnormalities in dystrophin immunostaining are not easily observed and are more frequent in manifesting carriers, when the muscle is grossly altered.

Adolescent↗
PubMed1991

Passive avoidance behaviour deficit in the mdx mouse.

Thirty per cent of boys with Duchenne muscular dystrophy (DMD) suffer from various degrees of mental retardation. Since dystrophin, the protein absent in muscles of boys with DMD, is produced also in the brain, it was postulated that the deficiency of brain dystrophin might account for the mental retardation found in DMD boys. The mdx mouse, a mouse model of DMD, fails to produce dystrophin in muscle and brain. This prompted us to study the cognitive function of these animals. Learning and memory processes were studied in 10 mdx females and 9 genetically matched controls using the passive avoidance test. Statistically significant differences in the retention of the passive avoidance response was detected between mdx and control mice, indicating an impairment in passive avoidance learning in mdx mice. Our data reinforce the view that brain dystrophin deficiency is correlated with cognitive dysfunction and indicate that mdx mice might be a model for the mental retardation found in DMD boys.

Animals↗
PubMed1995

The effect of glucocorticoids on the accumulation of utrophin by cultured normal and dystrophic human skeletal muscle satellite cells.

Human muscle cultures undergo a long-term loss of myotubes and a decline in dystrophin content, which can be prevented by glucocorticoid treatment of the cultures. We confirmed these findings and extended them to show that the utrophin content of control and dexamethasone-treated normal myotube cultures is not significantly different. In contrast to normal cultures, the utrophin content of long-term dexamethasone-treated DMD myotube cultures was significantly greater than that of the corresponding untreated cultures. Utrophin mRNA transcript levels normalized to total poly (A) were unaffected by dexamethasone treatment of either normal or DMD myotube cultures, suggesting the effect of dexamethasone on utrophin accumulation by DMD cultures is mediated post-transcriptionally. A combination of an increase in myotube numbers and lack of competition with dystrophin for membrane-binding sites in DMD myotubes may explain the distinct effects of dexamethasone on utrophin levels in normal and DMD cultures.

Cells, Cultured↗
PubMed1994

Mutation of dystrophin gene and cardiomyopathy.

The correlations between the type of gene mutation and the cardiac clinical picture were examined in 284 patients with dystrophinopathy (200 Duchenne and 84 Becker). The subjects with normal heart showed deletions including exons 48-49 in 21.4% DMD and in 25% BMD, and other deletions in 35.7% DMD and 25% BMD; vice versa the cases with severe cardiac involvement showed deletions including 48-49 in 38.8% DMD and 37.5% BMD and other deletions in 32.9% DMD and 20% BMD. The age of death was 18 years in DMD patients with deletions including 48-49 whereas the age was about 22 in the cases with other deletions. The differences were statistically significant.

Adolescent↗
PubMed1996

Multifrequency bioelectric impedance measurements for predicting body water compartments in duchenne muscular dystrophy.

Body hydration and extra- to intra-cellular water ratio (ECW: ICW) have been studied in 12 duchenne muscular dystrophy (DMD) patients and 15 healthy controls. Subjects underwent total body water (TBW) and extracellular water (ECW) assessment by deuterium and bromide dilution, respectively. Multifrequency bioelectric impedance analysis (MFBIA) was performed on all subjects with the aim to establish its accuracy in predicting TBW and ECW in DMD. Body hydration was lower (51.8 +/- 2.8 vs 58.5 +/- 5.9%, P < 0.01) and the ECW: ICW ratio higher (1.15 +/- 0.25 vs 0.70 +/- 0.23, P < 0.001) in DMD than in control subjects. Hence, control-generated formulae for predicting TBW and ECW from MFBIA gave inaccurate results in DMD subjects. Population-specific formulae were developed to obtain an accurate prediction of body water compartments in DMD patients.

Adolescent↗