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Biomedical subjects

V Dubowitz

Publications and source records attributed to V Dubowitz.

At least 181 records · Page 10Linked to original sources
PubMed1987

DNA deletions in mild and severe Becker muscular dystrophy.

The DNA of 33 patients diagnosed as suffering from Becker muscular dystrophy (BMD) has been probed with cloned DNA sequences from Xp21, known to reveal DNA deletions in patients suffering from the more severe Duchenne muscular dystrophy (DMD). Two BMD cases showed clear deletions. A third case gave aberrant band sizes, which further analysis showed to be caused by a small deletion. This suggests that deletions in DXS164 occur approximately as frequently in BMD as they do in DMD. Of the two cases showing large deletions, one is at the severe end of the Becker clinical spectrum, whilst the other is a classical Becker-type dystrophy. The fact that loci defined by probes commonly deleted in classical DMD patients are also deleted in BMD patients of varying severity is strong additional evidence that these disorders are allelic, and further justifies the use of probes with defined linkage relationships to DMD also being used for counselling in BMD families.

Adolescent↗
PubMed1987

Immunocytochemical localisation of complement components C8 and C9 in human diseased muscle. The role of complement in muscle fibre damage.

The localisation of the complement components C8 and C9 was studied immunocytochemically in human diseased muscle to determine the role of complement in muscle fibre damage. Monoclonal antibodies to 2 epitopes of C9 and a monoclonal antibody to the alpha subunit of C8 were applied to frozen sections of muscle biopsies from 9 cases of dermatomyositis, 5 cases of polymyositis, 7 cases of Duchenne muscular dystrophy and 4 cases of Becker muscular dystrophy. These were compared with 6 control biopsies which were morphologically normal. In all cases of inflammatory myopathies several non-necrotic fibres showed discrete peripheral patches of C9 and to a lesser extent C8. In the muscular dystrophies peripheral C9 was observed on a few non-necrotic fibres and basophilic fibres showed C9 between the fibres as well as at the periphery. In all cases necrotic fibres labelled intensely with C9 and C8 but intensities varied with the different monoclonal antibodies. This was thought to result from differences in the polymerisation of the C9 molecule in the membrane attack complex. Complement C8 and C9 were also localised to blood vessels in 3 cases of muscular dystrophy, 2 cases of polymyositis and all cases of juvenile dermatomyositis. No complement was observed in the control samples. Our results provide evidence for the sublytic formation of the membrane attack complex (MAC) on non-necrotic fibres in inflammatory myopathies and muscular dystrophy. This sublytic formation of the MAC may induce sublethal metabolic damage, mediated by calcium, and suggests a primary role of complement in muscle damage not only in inflammatory disorders but also muscular dystrophy.

Adolescent↗
PubMed1987

Cerebral ventricular dilation in congenital myotonic dystrophy.

Ultrasonography or computed tomography scanning of the brain was performed in 10 infants with congenital myotonic dystrophy between the age of 1 day and 2 months, and showed intracranial abnormalities in all. Ventricular dilation was diagnosed in eight (80%), subarachnoid hemorrhage in one, and white matter infarcts in one. The common finding of ventricular dilation is probably related to developmental brain abnormality dating back to fetal life, because it was already present in three infants scanned on the first day of life. Neonatal asphyxia was present in seven infants, associated with intraventricular hemorrhage in two. The relationship between these changes and mental retardation, which is a common feature in this disease, is unclear.

Cerebral Ventricles↗
PubMed1987

Neurological, electrophysiological and MRI abnormalities in infants with extensive cystic leukomalacia.

Twenty infants, diagnosed by cranial ultrasound as having extensive cystic leukomalacia, had visual evoked responses (VER) and electroencephalograms (EEG) in the neonatal period and MRI scans later in infancy. The early ultrasound findings and results from the electrophysiological tests were correlated with later MRI findings and functional abilities. In infants with periventricular leukomalacia (PVL), the cysts were usually no longer visible by ultrasonography, beyond 40 weeks postmenstrual age (PMA), but later MRI scans showed a consistent pattern of delayed myelination around the irregularly dilated occipital horns of the lateral ventricles. VER's were present in the neonatal period and vision was maintained, although all infants developed a marked squint. EEG's were either normal or abnormal initially, but improvement was noted within several weeks. In those with subcortical or mixed lesions, cysts were noted to persist beyond 40 weeks PMA. Later MRI scans showed very poor myelination, with poor progress on subsequent scans and cortical atrophy. VER's were absent and all infants later became cortically blind. EEG's were severely abnormal and recovery was very poor. The infants with PVL developed spastic diplegia with moderate developmental delay, while those with mixed or subcortical lesions developed quadriplegia with severe mental retardation. An integrated approach, consisting of ultrasound imaging and electrophysiological recordings in the neonatal period and MRI imaging later in infancy, may provide a more reliable prediction of the pattern of later deficits.

Brain↗
PubMed1987

Continuous 4-channel EEG monitoring: a guide to interpretation, with normal values, in preterm infants.

A system is described for the rapid analysis of the extensive EEG data produced by continuous 4-channel monitoring. Using this system, the initial EEGs of 44 low-risk preterm infants between 26 and 37 weeks gestation have been analysed and quantified in order to establish standard values. This provides a basis for assessment of the acute EEG as an index of cerebral function in high-risk or abnormal preterm infants.

Brain↗
PubMed1987

A syndrome with juvenile cataract, cerebellar atrophy, mental retardation and myopathy.

Four patients of two families with clinical characteristics resembling those in Marinesco-Sjögren syndrome are presented. All patients had infantile hypotonia as the presenting sign. In preschool age ataxia, cataract and mental retardation manifested. CT scan revealed cerebellar atrophy. Muscle biopsy showed myopathic changes with vacuolar degeneration and marked adipose tissue proliferation. Electron microscopy showed myelin bodies and autophagic vacuoles. The conclusion is that the peculiar myopathic and degenerative findings in the muscle biopsy are a consistent morphological feature in the clinical entity of the patients and the syndrome is distinctive from Marinesco-Sjögren syndrome.

Adolescent↗
PubMed1987

Continuous four-channel EEG monitoring in the evaluation of echodense ultrasound lesions and cystic leucomalacia.

Continuous monitoring by electroencephalography (EEG) was performed in 31 preterm infants with echodense ultrasound lesions using the Oxford Medilog four channel recorder. In 12 infants these densities preceded cyst formation, eight in the periventricular and four in the subcortical region. In the 19 other infants the densities resolved. The most severe EEG depression occurred in the four infants with subcortical cysts, who also had the poorest outcome. Six of eight infants with periventricular lesions had lesser degrees of abnormality though all infants had moderate to severe handicap at follow up. Similar abnormalities were seen on EEG recording in three infants in whom the densities resolved without cyst formation and these infants also had an abnormal outcome. An abnormal EEG recording provides a sensitive early guide to the severity and prognosis of these lesions, even before they can be seen on ultrasonography.

Brain Ischemia↗
PubMed1987

The application of linkage analysis to genetic counselling in families with Duchenne or Becker muscular dystrophy.

A total of 278 families of probands with Duchenne or Becker muscular dystrophy has been ascertained and offered genetic counselling. Linkage studies have been performed in these families using polymorphic DNA markers identifying loci linked to Duchenne and Becker muscular dystrophy. The clinical features of the probands are discussed: there was marked intrafamilial resemblance in the severity of the disease. We estimate that a complete study of potential carriers in these families would require analysis of samples from approximately 1400 subjects. The results of linkage studies tended to move women's carrier risk estimates (based on CK and pedigree data) towards the extremes of the risk categories, providing a more definitive risk estimate for 81% of the women who were previously in the middle range of carrier risk probabilities. About 70% of the families had only one affected member. Linkage analysis altered carrier risk estimates in 95% of sisters and aunts of index cases, but only affected estimates of the mother's carrier risks in about 11% of isolated cases. Even where linkage studies were not helpful in elucidating carrier risks, information could usually be obtained for use in prenatal diagnosis if required. We have assessed the attitudes to pregnancy and prenatal diagnosis of women at risk of being carriers of Duchenne or Becker muscular dystrophy and report 17 pregnancies in these women.

Amniocentesis↗
PubMed1987

An unusual case of neonatal myasthenia.

An unusual case of neonatal myasthenia gravis is reported in an infant who had respiratory failure due to diaphragmatic weakness. Although power and tone in the limbs were normal, fatiguability of both diaphragm and peripheral muscles was demonstrated. Acetylcholine receptor antibodies were absent in the mother, which suggests that an alternative humoral mechanism may have been responsible for the transient (6-week) neonatal weakness.

Female↗
PubMed1987

Ultrasound imaging and directed needle biopsy in the diagnosis of selective involvement in muscle disease.

Four children investigated for neuromuscular disorder by routine ultrasound imaging showed selective involvement within the quadriceps femoris muscle, with involvement of the vasti and sparing of the rectus femoris. This was confirmed by concurrent needle biopsy of the two muscles. Real-time ultrasound imaging is quick, noninvasive, readily accepted by children, and has the advantage over CT scans of being practical for routine outpatient use. Needle biopsy is relatively atraumatic and enables one to select specific superficial and deep muscles for concurrent biopsy.

Adipose Tissue↗
PubMed1987

The role of Coxsackie B viruses in the pathogenesis of myocarditis, dilated cardiomyopathy and inflammatory muscle disease.

Coxsackie B viruses are members of the family Picornaviridae which have been associated by retrospective serology with a range of muscle diseases, particularly myocarditis, dilated cardiomyopathy and epidemic pleurodynia (epidemic myalgia or Bornholm disease). It has been proposed that virus-induced myocarditis disposes to the development of idiopathic dilated cardiomyopathy. However, despite many attempts, isolation of infectious virus or immunofluorescent detection of virus-specific antigens in the affected tissue is rare, although virus may be found in faeces early in infection. This discrepancy awaited the development of nucleic acid probes to resolve the problem of whether virus was present consistently in myocardium or other muscle tissues. We report here the synthesis of Coxsackie B virus-specific complementary DNA (cDNA) probes and their use in molecular hybridizations to quantitative slot-blots of RNA prepared from either endomyocardial or skeletal muscle biopsy specimens. Of 50 patients with histologically proven myocarditis or dilated cardiomyopathy, 28 (56%) had an endomyocardial biopsy specimen positive for the presence of Coxsackie B virus-specific RNA. Twenty-two patients with other cardiac diseases of known aetiology, unrelated to virus infection, were all negative. Multiple biopsies were obtained from 20 patients with myocarditis or dilated cardiomyopathy and 15 of these (75%) had at least one biopsy specimen positive, indicating the focal nature of the disease. In analogous investigations, Coxsackie B virus-specific RNA was detected in four out of seven single skeletal muscle biopsy specimens from patients suffering from juvenile dermatomyositis, and one out of two patients with adult polymyositis. Ten muscle controls, either normal or Duchenne muscular dystrophy, were negative for virus RNA.

Cardiomyopathy, Dilated↗
PubMed1986

A balanced de novo X/autosome translocation in a girl with manifestations of Lowe syndrome.

The Oculo-cerebro-renal syndrome of Lowe is an X-linked recessive disorder characterised by mental and growth retardation, renal rickets with renal tubular acidosis, generalised aminoaciduria, hypotonia, cataracts, glaucoma and frontal bossing. Manifestations of this syndrome were seen in a girl with no family history of the disorder, but who was found to have a de novo balanced X/3 translocation, with a breakpoint at Xq25. She had also inherited a balanced 14/17 translocation from her father. It is postulated that the clinical picture may be the result of disruption of the X chromosome within the gene at the locus for Lowe syndrome, with non-random inactivation of the normal X, which may permit the expression of this X-linked recessive disorder in a girl.

Child↗
PubMed1986

A linkage study of Emery-Dreifuss muscular dystrophy.

We have searched for linkage between polymorphic loci defined by DNA markers on the X chromosome and X-linked Emery-Dreifuss muscular dystrophy (EDMD). There are high recombination rates between EDMD and the Xp loci known to be linked to Becker and Duchenne muscular dystrophy. There is a suggestion of linkage between EDMD and the loci DXS52 and DXS15, defined by probes St14 and DX13 respectively, located at Xq28. Z for DXS15 = 1.14 at theta = 0.15. This is in agreement with the previously reported linkage between a disorder strongly resembling EDMD and colour-blindness (Thomas et al. 1972), suggesting that there is a second locus on the X chromosome concerned with muscle integrity.

Adolescent↗
PubMed1986

Effects of posture and spinal bracing on respiratory function in neuromuscular disease.

Effects of posture and spinal bracing on lung function were studied in 40 children with neuromuscular disease, 20 of whom had scoliosis and were non-ambulant. Change from sitting to supine position had little effect on lung function in ambulant children, but caused a significant 12% reduction in forced vital capacity in a group of 16 non-ambulant children with scoliosis, suggesting diaphragmatic weakness in some. Spinal bracing, using a rigid supporting jacket, resulted in a significant reduction in mean vital capacity of 22%. The degree of impairment in forced vital capacity was proportional to the severity of the scoliosis (as measured by the Cobb's angle), to the amount of correction achieved by the brace, and to the degree of diaphragmatic weakness. Spinal bracing in a child with established severe scoliosis causes appreciable respiratory impairment, and this may explain why it is less likely to be tolerated than early prophylactic bracing.

Braces↗
PubMed1986

Low serum thyroxine concentrations and neural maturation in preterm infants.

The effect of hypothyroxinaemia on postnatal progression of the motor nerve conduction velocity was studied in 33 very low birthweight infants. Serum concentrations of thyroid stimulating hormone, triiodothyronine, and thyroxine were determined at birth and at ages 3, 7, and 21 days. Nerve conduction velocity was measured in the first week of life, on day 21, and at 40 weeks' postmenstrual age. Seven infants maintained their thyroxine concentration above 60 nmol/l (4.67 micrograms/100 ml) throughout the study. Three of these infants needed mechanical ventilation and one had an intraventricular haemorrhage. Twenty six infants developed hypothyroxinaemia (thyroxine less than 60 nmol/l). The nerve conduction velocity was delayed in 13 infants, two on day 21 and 11 at 40 weeks' postmenstrual age. The delay was equivalent to 1.9-4.4 weeks. All these infants belonged to the group with depressed thyroxine concentrations. The delay in progression in nerve conduction velocity was associated with prolonged hypothyroxinaemia, especially in those infants who also required ventilation. Further studies are in progress to study the effect of thyroid hormone on the nerve conduction velocity in preterm infants.

Aging↗
PubMed1986

A de novo X;13 translocation with abnormal phenotype.

We describe a female infant who presented with hypotonia and developmental delay. Her karyotype showed a de novo balanced translocation between the X chromosome and chromosome 13, with breakpoints at Xq13 and 13p11. The normal X was late replicating in all cells examined. The cause of this patient's abnormal phenotype is discussed.

Adult↗
PubMed1986

The screening of Duchenne muscular dystrophy patients for submicroscopic deletions.

We have probed the DNA of 156 Duchenne muscular dystrophy (DMD) patients, representing 140 kindreds, with cloned DNA sequences derived from Xp21 and known to show deletions in some DMD patients. Sixteen cases showed a deletion, as defined by lack of hybridisation to one or more of the four probes used. However, two of these cases were brothers, so 15 independent deletions (10.7%) are represented. The deletion map is compatible with the suggested order for the sites of the probes used in the study, that is, telomere----pERT87.15----pERT87.8----pERT87.1----pX J1.1----754----centromere. Further mapping of these deletions and characterisation of the deletion breakpoints should facilitate more accurate molecular localisation of the gene or genes which, when mutated, are responsible for causing DMD.

Chromosome Deletion↗