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Biomedical subjects

V Dubowitz

Publications and source records attributed to V Dubowitz.

At least 127 records · Page 7Linked to original sources
PubMed1992

Experimental regeneration in canine muscular dystrophy--1. Immunocytochemical evaluation of dystrophin and beta-spectrin expression.

The expression of dystrophin and beta-spectrin was examined from 1 to 56 days in regenerating muscle fibres in normal and dystrophic dogs, following necrosis induced by the venom of Notechis scutatis. Normal and dystrophic dog muscle regenerated at an equal rate and new myotubes were present in both at the periphery of necrotic fibres by 3 days. In normal dogs dystrophin was detected in the sarcoplasm of the regenerating fibres by 3 days and was localized to the plasma membrane by 4 days. The localization of dystrophin is independent of beta-spectrin and was detected before beta-spectrin, which was not observed until 5-6 days. Normal peripheral labelling of both was restored by 14 days in normal dogs. Normal beta-spectrin labelling of regenerating dystrophic fibres was also restored by 14 days and is not dependent on the presence of dystrophin in dystrophic dogs. A proportion of regenerating fibres in normal and dystrophic dogs showed weak immunolabelling of beta-spectrin prior to 14 days. This is a feature of immature muscle fibres. Antibodies to different domains of dystrophin bound to the periphery and sarcoplasm of regenerating fibres in dystrophic dogs, particularly during the first 7 days of regeneration, but the fluorescence was less intense than in normal dogs. Weak labelling with antibodies corresponding to the C-terminus of the rod domain of dystrophin persisted on dystrophic regenerating fibres up to 21 days. This may relate to developmental isoforms of dystrophin.

Animals↗
PubMed1992

A randomized controlled trial of early surgery in Duchenne muscular dystrophy.

We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment.

Biopsy↗
PubMed1992

The effect of pethidine on the neonatal EEG.

Thirty-two preterm infants were monitored with an on-line cotside EEG system for periods of up to nine days. Changes in the normal pattern of discontinuity of the EEG were seen in association with pethidine administration. The duration of the EEG suppression after pethidine administration was greatest after the first dose and progressively less with subsequent doses. It was not related to the gestational maturity or postnatal age at which the dose was given. This system of EEG analysis allowed recognition of this previously undescribed effect of pethidine on the neonatal EEG, and should have application to monitoring the effects of brain function of other drugs in routine neonatal practice.

Brain↗
PubMed1992

Subclinical cardiomyopathy in Becker muscular dystrophy.

OBJECTIVE: To investigate the prevalence, age distribution, and spectrum of cardiac involvement in a cohort of patients with Becker muscular dystrophy. DESIGN: A prospective non-invasive study with clinical, electrocardiographic, and echocardiographic assessment. PATIENTS: 19 patients (age range 16-41 years) with Becker muscular dystrophy attending the Muscle Clinic at Hammersmith Hospital and 22 healthy controls (age range 22-36 years). RESULTS: 17 patients (89%) were symptom free; two had exertional dyspnoea. Three had a past history of acute pericarditis. The electrocardiogram was abnormal in 14 patients (74%). Intraventricular conduction delay or right bundle branch block was present in eight (42%). Three (16%) had tall R waves (R/S > 1) in lead V1 in the absence of right bundle branch block and eight (42%) had Q waves in the lateral and inferolateral leads. The PQ interval was significantly shorter in patients with Becker muscular dystrophy (p < 0.01). Echocardiography showed left ventricular dilatation in seven patients (37%) and 12 (63%) had subnormal systolic function caused by global hypokinesia (fractional shortening < 27%). Six of these patients were under the age of 22 years. Patients with Becker muscular dystrophy had significant reduction of both fractional shortening and corrected mean velocity of circumferential shortening compared with controls. No correlation was found between fractional shortening and age. The third filling fraction was significantly reduced in patients with Becker muscular dystrophy (p < 0.05), although other indices of diastolic function (isovolumic relaxation time and E/A ratios) were not significantly different. CONCLUSIONS: Though most patients with Becker muscular dystrophy were symptom free, a high percentage had evidence of a subclinical cardiomyopathy. Electrocardiography showed that the inferolateral and posterior segments of the left ventricle tended to be affected and may show evidence for conduction tissue disease. Echocardiography showed that most patients had left ventricular dilation and global hypokinesia. The severity of left ventricular disease was unrelated to age; some younger patients had severe left ventricular dysfunction. All patients with Becker muscular dystrophy should have echocardiographic assessment of left ventricular function.

Adolescent↗
PubMed1992

Prenatal prediction of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common cause of inherited morbidity and mortality in childhood. The wide range of phenotypes in SMA, uncertainty regarding its mode of inheritance, and the suggestion of linkage heterogeneity have complicated the genetic counselling of parents of affected children. The locus responsible for autosomal recessive SMA has been mapped to 5q11.2-q13.3. The most likely order of loci is cen-D5S6-(SMA,D5S125)-(JK53CA1/2,D5S112)-D5S3 9-qter, with highly polymorphic loci being identified at JK53CA1/2 and D5S39. We describe linkage studies with another highly polymorphic locus, D5S127, that is closely linked to D5S39. This genetic map can be used as the basis for genetic counselling in families with autosomal recessive SMA. Appropriate allowance can be made for sporadic cases owing to non-inherited causes and for linkage heterogeneity or misdiagnoses.

Base Sequence↗
PubMed1992

"Catch-up" growth in steroid dependent dermatomyositis treated with cyclosporin-A.

OBJECTIVE: To improve the short-term growth, and hopefully final height attainment, of children with dermatomyositis treated with chronic daily corticosteroid regimens. METHODS: We have examined the growth of nine pre-pubertal children (7F, 2M), mean age 8.9 (range, 5.7-12.3) years, who had severe juvenile dermatomyositis and required persistent corticosteroid therapy. All were treated with cyclosporin-A. RESULTS: During a mean period of 1.3 years (range 1.0-1.7) cyclosporin-A treatment was associated with a marked decrease in the dosage of prednisolone, from a mean of 12.4 to 6.6 mg/day (p < 0.02), and an increase in height velocity standard deviation score from a mean of -1.37 to +1.39 at 6 months (p < 0.02) and -0.33 at one year. During the first year of treatment with cyclosporin-A, seven patients were able to either withdraw or reduce their prednisolone dose. No side effects of treatment were observed. CONCLUSIONS: Cyclosporin-A was a useful treatment modality in juvenile dermatomyositis and allowed a decreased dose of corticosteroids and associated "catch-up" growth.

Body Height↗
PubMed1992

Dystrophin in frameshift deletion patients with Becker muscular dystrophy.

In a previous study we identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. We have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases we detected slightly lower-molecular-weight dystrophin in 12%-15% abudance relative to the normal. By sequencing amplified mRNA we have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternative splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame.

Adolescent↗
PubMed1991

Characterisation of dystrophin in carriers of Duchenne muscular dystrophy.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, was studied in needle biopsy samples taken from the quadriceps muscle of 15 asymptomatic carriers of DMD (13 adults and 2 young girls) and one symptomatic adult carrier. Antibodies to N- and C-terminal regions of dystrophin were used for both Western blot analysis and immunocytochemistry and a monoclonal antibody to beta-spectrin used to assess membrane integrity. All asymptomatic adult carriers showed some abnormality in dystrophin immunostaining but very few negative fibres were present. A clear mosaic of dystrophin positive and negative fibres was seen only in the adult symptomatic carrier and the two young girls. On a Western blot, all carriers studied had dystrophin of normal molecular weight, but most had reduced abundance. In adult carriers, the amount of dystrophin relative to normal controls varied, but it was unrelated to age, serum creatine kinase (CK) levels or to the degree of pathology. Carriers with normal CK showed abnormalities in dystrophin expression. The dystrophin immunoblotting profile of the 2 young girls was very similar to that of their mothers, but the mosaic pattern of immunostaining was not apparent in the older carriers. In conclusion, dystrophin immunostaining and Western blot analysis of biopsy samples from asymptomatic carriers is often abnormal and they may be useful additional aids for establishing carrier status, particularly in younger girls.

Adult↗
PubMed1991

Fatal rhabdomyolysis complicating general anaesthesia in a child with Becker muscular dystrophy.

A 6-yr-old boy who presented with brown urine due to myoglobinuria and who was otherwise virtually asymptomatic was diagnosed as having Becker muscular dystrophy on the basis of a greatly elevated creatine kinase, muscle biopsy, dystrophin analysis, and a deletion of exons 3-7 in the dystrophin gene. Fifteen months later, during a general anaesthetic for dental treatment, he had a cardiac arrest associated with acute rhabdomyolysis, hyperkalaemia and hypocalcaemia. He died 4 days later. This case is reported to highlight this rare but potentially fatal complication of anaesthesia in muscular dystrophy, and to discuss possible ways of preventing such a catastrophe.

Anesthesia, Dental↗
PubMed1991

Molecular studies of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is inherited as an autosomal recessive disorder which presents as a severe, intermediate or mild condition. The disease selectively affects the alpha motor neuron but nothing is as yet known about the underlying biochemical defect. Recent genetic studies have mapped all three types of SMA to the same region of human chromosome 5 (5q11.2-q13.3) raising the possibility that the mutations may be allelic. Polymorphic DNA markers have been characterised which are suitable for prenatal diagnosis. This is the first step in the isolation of the mutant gene (or genes) involved in this disorder.

Animals↗
PubMed1991

Dystrophin abnormalities in polymyositis and dermatomyositis.

The expression of dystrophin in muscle biopsies from nine cases of polymyositis, ten cases of juvenile dermatomyositis and three adults with dermatomyositis was studied by Western blot analysis and immunocytochemistry. Five antibodies corresponding to different N- and C-terminal regions of the dystrophin gene were used. Sixteen of the 22 cases (73%) showed an abnormality in the expression of dystrophin on Western blot analysis, either with a reduced molecular weight protein or a reduced amount. Immunostaining was abnormal in 11 out of 19 cases (58%) and showed varying degrees of discontinuity or loss of sarcolemmal staining. Immunolabelling of these areas with antibodies to beta-spectrin was normal implying that the changes were not caused by a loss of the sarcolemma. These results show that secondary changes in the expression of dystrophin can occur in the absence of an abnormality in the corresponding gene and that dystrophin cannot be used in isolation as a diagnostic marker for muscular dystrophy.

Adolescent↗
PubMed1991

Renal haemodynamics of cyclosporin A nephrotoxicity in children with juvenile dermatomyositis.

1. Renal haemodynamics were monitored over an average period of 19 months in 17 children being treated with cyclosporin A. Sixteen had juvenile dermatomyositis and one had chronic polyneuropathy. The dose of cyclosporin A ranged from 2.3 to 8.3 mg day-1 kg-1 (median 4.1 mg day-1 kg-1). 2. Glomerular filtration rate (expressed in terms of extracellular fluid volume), renal blood flow (expressed as a fraction of cardiac output) and filtration fraction were measured by using 99mTc-labelled diethylenetriamine-penta-acetate. They were compared with the dosage and trough blood levels of cyclosporin A, and, in 15 patients receiving prednisolone in addition to cyclosporin A, with steroid dosage. 3. All 17 children had a renogram performed 6 months after starting cyclosporin A treatment. Nine of them also had a renogram before starting cyclosporin A treatment (baseline study), while 13, in addition to their renogram 6 months after starting cyclosporin A treatment, also had at least one further renogram. 4. Glomerular filtration rate/extracellular fluid volume fell slightly but significantly from 0.009 (SD 0.0013) before starting cyclosporin A treatment to 0.0085 (0.002) min-1 (P less than 0.01) 6 months after cyclosporin A treatment in the nine children who underwent a baseline study. This was accompanied by a significant (P less than 0.001) fall in filtration fraction from 0.108 (0.015) to 0.088 (0.014). However, renal blood flow/cardiac output showed no change. 5. In the 13 children studied beyond 6 months after starting cyclosporin A treatment, there was no further significant overall change in any renal haemodynamic variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗