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Biomedical subjects

D Hilton-Jones

Publications and source records attributed to D Hilton-Jones.

At least 37 records · Page 2Linked to original sources
PubMed1995

Muscle X-inactivation patterns and dystrophin expression in Duchenne muscular dystrophy carriers.

Muscle pathology, dystrophin expression and X-inactivation patterns were studied in the muscle of five asymptomatic females heterozygous for deletions in the dystrophin gene (non-manifesting carriers) and five symptomatic carriers (manifesting carriers). Muscle from the non-manifesting carriers showed an increase in the population of centrally nucleated fibres (9.0 +/- 2.8%; controls, 1.4 +/- 0.3%), frequent fibers with abnormally interrupted dystrophin staining (38 +/- 5%), and, in sections from three individuals, small numbers of dystrophin-negative fibers (1-4%). The amount of dystrophin measured by immunoblotting was reduced to 64 +/- 5% (P < 0.001 n = 5) of normal. The pattern of X-inactivation in muscle DNA was non-biased (50: 50-60: 40) in all cases. In the manifesting carriers both highly biased (90: 10) and non-biased patterns of X-inactivation were found, but no consistent relationship was apparent between the patterns of X-inactivation and the proportions of dystrophin-negative fibers. We conclude from studies of the non-manifesting carriers that the proportion of residual dystrophin is similar to the relative activation in muscle of the X-chromosome carrying the wild-type allele. Extreme bias of X-inactivation can be associated with early clinical symptoms and severe pathology. However, as non-manifesting and some manifesting adult carriers had identical patterns of X-inactivation, abnormalities in the distribution of dystrophin, as well as overall levels of expression, may be important for the development of myopathic pathology.

Adolescent↗
PubMed1995

Recurrent congenital arthrogryposis leading to a diagnosis of myasthenia gravis in an initially asymptomatic mother.

We report a sibship in which the syndrome of congenital arthrogryposis occurred in two male and two female neonates, three of whom died. The mother was asymptomatic at the time of the first pregnancy and the subsequent development of muscle weakness was later confirmed to be due to myasthenia gravis. The literature on this association is briefly reviewed and the extremely high risk of recurrence of this complication in subsequent pregnancies is addressed.

Adult↗
PubMed1995

Spontaneous intracranial hypotension.

The clinical features and radiological appearances of spontaneous intracranial hypotension are described in three patients and the medical literature is reviewed. Awareness of this condition and its differentiation from more sinister meningitic processes is important to avoid unnecessary invasive investigations and to allow prompt diagnosis and effective treatment.

Adult↗
PubMed1994

Comparison of the relative levels of the 3243 (A-->G) mtDNA mutation in heteroplasmic adult and fetal tissues.

In this report, levels of the 3243 A to G mtDNA mutation associated with the mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome were measured in different heteroplasmic tissues of subjects in a kindred including adults with variable clinical phenotypes and a fetus. The relative proportions of mutant mtDNA varied widely (0.03 to 0.67) between identical tissues of the six different subjects and between different tissues of the same subjects. In the one adult for whom sufficient data were available there was an apparent correlation between the distribution of mutant mtDNA and clinical presentation. A woman without neurological symptoms who died prematurely with a cardiomyopathy and lactic acidosis had higher proportions of mutant in heart (0.49, SD 0.02), skeletal muscle (0.56, SD 0.01), and liver (0.55, SD 0.12) than in other tissues studied (for example, kidney, 0.03, SD 0.01). A strikingly different result was found in a 24 week old fetus in whom there was little variation in heteroplasmy in different tissues (average proportion of mutant mtDNA in six tissues, 0.53, SD 0.02). These observations add cardiomyopathy to the growing list of presenting features of the 3243 mtDNA mutation. The unique results from the fetus suggest also that selection pressures acting on either wild type or 3243 mutant mtDNA (rather than variation from replicative segregation of the heteroplasmic mtDNA) may be responsible primarily for the variable levels of 3243 mutant mtDNA in different heteroplasmic tissues of adults.

Adult↗
PubMed1991

Type 2 fiber predominance in Lambert-Eaton myasthenic syndrome.

Serial muscle biopsies in a noncarcinomatous case of Lambert-Eaton myasthenic syndrome (LEMS) have shown progressive atrophy and loss of type 1 fibers, resulting in overwhelming type 2 predominance. A similar abnormality was found in a single biopsy from a second case of LEMS without associated carcinoma. Review of the literature suggests that type 2 fiber predominance has been observed in at least one other biopsied case. Interference with transmitter release caused by anti-voltage-gated calcium channel antibodies may deprive type 1 muscle fibers of the low frequency discharge necessary to maintain their metabolic properties.

Adolescent↗
PubMed1987

An unusual metabolic myopathy: a malate-aspartate shuttle defect.

Studies on a 27-year-old man with a 3-year history of exercise-induced muscle pain, passage of red urine and elevated serum creatine kinase are described. Histological examination of a biopsy from quadriceps revealed non-specific myopathic changes with occasional clusters of subsarcolemmal mitochondria. The phosphorylase stain was normal. Phosphorous nuclear magnetic resonance (NMR) spectroscopy studies of gastrocnemius and flexor digitorum superficialis muscles showed no abnormalities at rest. During aerobic exercise there was an abnormally rapid decrease in phosphocreatine concentration but the pH remained within the normal range. There was a build-up of phosphomonoester (probably glucose 6-phosphate), usually indicative of a block in glycolysis. However, a primary defect in the glycolytic pathway seemed unlikely because muscle acidified normally during ischaemic exercise. Recovery from exercise was unusual in that phosphocreatine resynthesis and inorganic phosphate disappearance followed similar prolonged time courses (in control subjects the rate of inorganic phosphate disappearance was about twice as fast as the rate of phosphocreatine resynthesis). The transport of inorganic phosphate into the mitochondria appeared to be delayed. These slow recovery data suggested that oxidative metabolism was impaired. However, with all substrates tested, isolated muscle mitochondria had rates of oxygen uptake that were similar to control values, thereby ruling out a primary defect in mitochondrial respiration. A system involving several mitochondrial transport systems, the malate-aspartate shuttle, was measured. The activity in the patient's isolated mitochondria was less than 20% of the activity present in samples from control subjects. This patient is the only one so far reported with a defect involving the malate-aspartate shuttle system.

Adult↗
PubMed1987

The study of human organs by phosphorus-31 topical magnetic resonance spectroscopy.

The potential clinical use of topical magnetic resonance spectroscopy (volume selection by static magnetic field gradients) was tested in 50 studies in volunteers. Topical magnetic resonance spectroscopy (MRS) was shown to be a straightforward method for localising 31P spectra of brain and liver. However, the spherical shape and fixed position of the selected volume posed serious limitations to the study of heart and transplanted kidney by topical MRS. Phosphorus-31 spectra of approximately 30 cm-3 of brain or liver could be obtained in 8 min. Ratios of metabolite concentrations could be determined with a coefficient of variation ranging from 10% to 30%. The ratios of phosphocreatine/ATP and inorganic phosphate/ATP in brain were 1.8 and 0.3, respectively. The ratio of inorganic phosphate/ATP in liver was 0.9. Intracellular pH was 7.03 in brain and 7.24 in liver. The T1 relaxation times of phosphocreatine, inorganic phosphate and gamma-ATP in brain were 4.8 s, 2.5 s and 1.0 s, respectively.

Brain↗
PubMed1986

Biochemical investigation of human tumours in vivo with phosphorus-31 magnetic resonance spectroscopy.

The bioenergetic state of 15 human tumours was examined with phosphorus-31 magnetic resonance spectroscopy. A striking diversity in metabolic patterns was observed, and significant differences from normal tissue were seen in all cases. A common feature was an elevation of intracellular pH, which may be related to an increase in Na+/H+ exchange during cell activation. It is unlikely that the patterns observed directly correlate with malignancy, but characterisation of the energetic state of a given tumour in a given physiological environment may help in the design and evaluation of interventions for that specific case.

Adult↗
PubMed1985

Non-penetrating arterial trauma and cerebral infarction in the young.

In a retrospective study of 60 patients under the age of 45 with ischaemic stroke the commonest likely predisposing factor was trauma, which applied to 13 (22%) patients. In 9 of these patients neck movement was the most likely factor that precipitated the stroke and was the factor identified in all the 3 who had damage to the vertebral artery. The other 4 patients had sustained direct trauma in the neck area, 2 as a result of attempted strangulation and 2 by carrying heavy loads on the shoulder. There may be a delay between the traumatic event and manifestation of the stroke, probably because the initial damage, which is most likely a small tear, is of no immediate consequence, and the stroke results after thrombus has formed over the tear and subsequently embolised.

Adult↗
PubMed1985

The causes of stroke in the young.

In a group of 75 patients under the age of 45 years with stroke, ischaemic cerebral infarction was diagnosed in 60 patients and primary intracerebral haemorrhage in 15. Trauma was found to be the commonest identifiable predisposing factor to cerebral infarction, being present in 13 cases (22%). Migraine was the second most commonly identified predisposing factor while atheroma and hypertension were infrequent. Such a high frequency of preceding trauma has not previously been described, perhaps because it is not generally appreciated that the delay between the traumatic event and subsequent stroke may be considerable. The diagnostic management of young stroke patients is considered with particular reference to the indications for specialized cardiac and neuroradiological investigations.

Adolescent↗
PubMed1985

A mitochondrial encephalomyopathy. A combined 31P magnetic resonance and biochemical investigation.

A 15-year-old girl presented with recurrent encephalopathic episodes, epilepsy, myopathy and chronic lactic acidosis. A muscle biopsy revealed the presence of ragged red fibres and mitochondria with paracrystalline inclusions. Biochemical studies on freshly isolated skeletal muscle mitochondria demonstrated a deficiency of NADH-CoQ reductase activity. Investigation of her gastrocnemius muscle at rest by phosphorus nuclear magnetic resonance displayed a reduced phosphocreatine concentration with elevated levels of inorganic phosphate and ADP. Abnormalities were also apparent in her brain spectrum. It is therefore possible that the mitochondrial defect present in skeletal muscle is also being expressed in the brain.

Adolescent↗
PubMed1983

Motor neuron disease in England and Wales, 1959-1979.

Mortality rates from motor neuron disease in England and Wales for the years 1959-1979 were studied through death certification data supplied by the Office of Population Censuses and Surveys. The age- and sex-adjusted mortality rate increased over the period from 1.2 per 100 000 per year in 1959-61 to 1.6 in 1977-79, the increase being most apparent in women over age 45 years and men over 60 years. The ratio of the sex-specific mortality rates remained fairly constant at 1.6:1 (male to female). The distribution of motor neuron disease deaths within England and Wales showed more variation between counties and between Hospital Regions than expected, and areas of high motor neuron disease mortality along the south coast and low mortality in the Midlands could be identified. The variation was most marked in those aged over 65 years at death. Examination of occupation, as listed on the death certificates, showed an excess of motor neuron disease deaths in leather workers in all three periods for which data were available (1959-63, 1970-72 and 1975). A small study of the certified cause of death of 56 motor neuron disease patients showed that a high percentage (88%) had motor neuron disease given as the cause of death.

Adult↗