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Biomedical subjects

R H Edwards

Publications and source records attributed to R H Edwards.

At least 181 records · Page 10Linked to original sources
PubMed1991

Muscle biochemistry and pathophysiology in postviral fatigue syndrome.

Patients with postviral fatigue syndrome (PVFS) usually complain of the skeletal muscle-related symptoms of fatigue and myalgia. It is not surprising therefore that the muscles have recently been the object of intensive studies which have used a variety of biochemical and physiological techniques. The aim of this chapter is to review these findings, and to discuss their significance or otherwise to the presenting symptoms and course of the condition.

Fatigue Syndrome, Chronic↗
PubMed1991

Phosphorus metabolites in the human placenta estimated in vivo by magnetic resonance spectroscopy.

Normal human placental metabolism has been studied in vivo by image localised 31P magnetic resonance spectroscopy in 13 women with anterior placentas; five, however, were too fat for useful spectral signals to be obtained. Magnetic resonance spectra of good quality which were considered to have arisen from the placenta were obtained from seven women with uncomplicated pregnancies (median gestational age 35 weeks, range 28-39). One other woman had a twin pregnancy in which one fetus had died a few days before. The phosphodiester signal from the placenta of the dead fetus was outside the 95% confidence intervals for normal placentas, suggesting that this technique may potentially be useful in the assessment of placental function.

Female↗
PubMed1991

Immune responsiveness in chronic fatigue syndrome.

We have endeavoured to find immunological indications of chronic virus infection in patients with chronic fatigue syndrome (myalgic encephalomyelitis) and to investigate immune responsiveness to viruses in such patients in comparison with normal subjects and patients with muscular dystrophy. Levels of circulating IgM immune complexes were elevated (above the 95% normal control range) in 10 (17%) of 58 patients with chronic fatigue syndrome, which was not significantly different from the normal controls or from dystrophy controls (by Mann Whitney U test). Levels of IgG complexes were only increased in 10% of patients. Lymphocyte proliferation in response to concanavalin A (Con A), assessed by increase in 3H-thymidine incorporation, did not differ between 14 patients and 18 normal subjects. The proliferative response to Coxsackie B virus antigen did not differ between chronic fatigue patients and normal subjects when expressed either as an increase in counts or as a stimulation index. Adjustment of the counts in relation to the proliferation response to Con A, as an indication of the overall proliferative response of the cell preparation, did not reveal any hidden difference. IgM antibodies to Coxsackie B viruses were not found in any of 20 patients and in 1 of 20 dystrophy controls. Significant levels of neutralizing antibodies to Coxsackie B viruses 1-5 were found in 6 out of 19 (32%) patients compared with 4 out of 17 (24%) dystrophy controls, which does not differ from currently expected normal incidence. Antibody titres to other respiratory viruses were also not notably different between the patient and control groups. In conclusion we can find no evidence for a definable viral aetiology for the chronic fatigue syndrome, neither in terms of a persistent infection nor an altered ability to respond to virus.

Adolescent↗
PubMed1991

Effects of calcium on protein turnover of incubated muscles from mdx mice.

Mdx mice have a genetic defect similar to that which causes Duchenne muscular dystrophy in humans. The influence of calcium on muscle protein metabolism of mdx and wild type (C57BL/10) mice was examined in vitro. Incubation of mdx muscles in a medium containing calcium at a concentration of 2.0 mM (but not 0.2 mM) resulted in proteolytic rates that were greater than those of C57BL/10 muscles. At 2.0 mM extracellular calcium, mdx muscle proteolysis was attenuated by thiol protease inhibitors but not by the weak base methylamine. Protein synthetic rates were higher in incubated mdx muscles than in incubated C57BL/10 muscles, but no effect of extracellular calcium concentration was observed in either strain. These data suggest that mdx mice have an abnormality of muscle calcium handling, which results in activation of nonlysosomal proteolytic processes but does not exert acute effects on protein synthetic rate.

Animals↗
PubMed1991

Creatine kinase and prostaglandin E2 release from isolated Duchenne muscle.

We studied the release of creatine kinase (CK) activity and prostaglandin E2 (PGE2) from isolated strips of biceps muscle from patients with Duchenne muscular dystrophy and nondystrophic control patients. CK release was significantly higher from the dystrophic samples than controls during the initial period of incubation, but this difference reduced with time of incubation. Immediate immersal of muscle strips into calcium-free bathing medium reduced the initial difference between the efflux from dystrophic and nondystrophic samples, whereas treatment with the calcium ionophore maintained the difference between the groups throughout the period of incubation (150 minutes). These results support the hypothesis that the lack of dystrophin in Duchenne muscle leads to damage to the tissue via a failure of calcium homeostasis. PGE2 release from the muscle strips followed a similar pattern to CK activity, supporting the possibility that, at least partly, the calcium-mediated damage involves activation of phospholipid hydrolysis.

Adolescent↗
PubMed1991

The quantitative study of lumbar vertebral bone marrow using T1 mapping and image analysis techniques: methodology and preliminary results.

A method of quantifying lumbar vertebral bone marrow using pixel by pixel T1 mapping of spin echo magnetic resonance images is described. The accuracy and precision of the relaxation time measurements is confirmed by studies with the EEC Concerted Research Project, test object no. 5. The T1 data from all the pixels sampled from lumbar vertebral marrow are displayed as a histogram. By "thresholding" relative to normal control data the spatial distribution of high or low T1 pixels can be demonstrated. The approach is superior to that of the conventional region of interest method for quantifying and analysing relaxation time data, and allows tissue heterogeneity to be studied. Studies in patients with aplastic anaemia and acute leukaemia have been performed.

Adult↗
PubMed1991

Tumour pH and response to chemotherapy: an in vivo 31P magnetic resonance spectroscopy study in non-Hodgkin's lymphoma.

Serial image-localized 31P magnetic resonance spectroscopy studies were performed in nine patients with newly diagnosed non-Hodgkin's lymphoma (NHL) during the early part of treatment with chemotherapy. The pre-treatment intracellular pH (pHi) of the tumours ranged from 6.97 to 7.61 for high-grade NHL (n = 3), and 7.16 to 7.39 for low-grade NHL (n = 5). A pH of 7.24 was recorded in a patient with intermediate-grade NHL. Slice-to-slice variation in tumour pHi in spectra obtained with a one-dimensional chemical shift imaging (1D-CSI) technique varied from zero to 0.5 pH units. The largest variation was seen in high-grade tumours. Slice-to-slice variation may reflect tumour heterogeneity. Alkaline shifts in tumour pHi of 0.14 to 0.45 pH units were seen in six patients following chemotherapy. Maximal change in tumour pH was related temporally to increases in the phosphodiester/beta-adenosine triphosphate ratio, and occurred before alterations in tumour size were documented. Cell death and necrosis may be associated with an alkaline shift in pHi due to cessation of H(+)-producing processes and release of basic components of proteins. An alkaline shift in tumour pHi may therefore be an early metabolic marker of response to chemotherapy.

Abdominal Neoplasms↗
PubMed1991

Domiciliary investigation of sleep-related hypoxaemia in Duchenne muscular dystrophy.

In Duchenne muscular dystrophy (DMD) nocturnal oxygen desaturation occurs during rapid eye movement (REM) sleep. Polysomnography, which requires hospital admission, will detect sleep-related breathing abnormalities. In order to avoid the inconvenience of hospital admission for the disabled patient, we investigated overnight oxygenation in ten boys with DMD by domiciliary oximetry. In four boys the results of oximetry were compared with those of a polysomnographic recording. The "repeatability" of domiciliary oximetry was assessed in six boys by performing oximetry on two non-consecutive nights. Older boys with DMD may develop a cardiomyopathy. In order to assess cardiac rhythm and ST segment changes we performed simultaneous Holter monitoring and oximetry in seven boys with overnight hypoxaemia. Six of the initial ten boys studied demonstrated episodic nocturnal hypoxaemia and there was a strong correlation between minimum oxygen saturation overnight and daytime arterial oxygen and carbon dioxide tensions (PaO2 r = 0.89; PaCO2 r = -0.87). Despite adequate REM time during polysomnography, greater oxygen desaturation was found during domiciliary oximetry. No difference was found in the severity of desaturation recorded in the boys who were studied on two separate occasions. Five boys demonstrated marked heart rate variation during hypoxaemic episodes and more serious arrhythmias occurred overnight in the three most hypoxaemic boys. Domiciliary oximetry is a simple, repeatable method of assessing overnight oxygenation and compares well with polysomnography. In boys with advanced DMD and severe nocturnal hypoxaemia, 24 h electrocardiographic monitoring may detect potentially life-threatening arrhythmias.

Adolescent↗
PubMed1990

Somatostatin mRNA and molecular forms during development of the rat retina.

The developmental control of rat retinal somatostatin (SS) expression was determined by Northern blot hybridization. The amount of SS transcript is higher than adult levels at embryonic day 16 and declines during late prenatal development. This pattern parallels the developmental expression of somatostatin immunoreactivity. The expression of somatostatin-immunoreactive peptide products using gel filtration chromatography was determined over the same period. Three molecular weight forms occur during development: a high m.wt. product and two smaller peptides which migrate with somatostatin-28 (SS28) and somatostatin-14 (SS14). SS14 is the peptide that predominates at all developmental time points, and is the only form detectable in the adult retina. The transient prenatal increase of somatostatin message and peptide suggests a role for this peptide in the developing retina.

Animals↗
PubMed1990

Molecular heterogeneity in McArdle's disease.

Biopsies were taken from a group of eleven patients with McArdle's disease, a congenital deficiency in muscle glycogen phosphorylase. The biopsies were screened by Western and Northern blotting for phosphorylase protein, phosphorylase-bound pyridoxal-5'-phosphate (the cofactor of the enzyme) and for phosphorylase mRNA. Of the eleven patients, three expressed phosphorylase mRNA at near normal levels and at the expected size. One of these patients also expressed low levels of phosphorylase protein that correlated with a small amount of measurable phosphorylase activity. These data support the contention of molecular heterogeneity in the presentation of this phenotype.

Antibodies, Monoclonal↗
PubMed1990

Energy dependence of cytosolic enzyme efflux from rat skeletal muscle.

(1) A recirculating isolated superfused skeletal muscle preparation has been developed for the study of rat soleus muscles at physiological temperature using 31P Nuclear Magnetic Resonance (NMR). (2) This system has been used to study intracellular muscle high energy phosphate content and pH during experimental damage to the muscle induced by 2,4-dinitrophenol, deoxycholate and the calcium ionophore, A23187. (3) Results indicate that release of intracellular cytosolic enzymes from damaged skeletal muscle may be induced by phosphocreatine (PCr) and adenosine trisphosphate (ATP) depletion, but under certain circumstances intracellular enzymes can be released from skeletal muscle without any fall in muscle PCr or ATP content.

2,4-Dinitrophenol↗
PubMed1990

Protein turnover is elevated in muscle of mdx mice in vivo.

mdx mice lack the protein dystrophin, the absence of which causes Duchenne muscular dystrophy in humans. To examine how mdx mice maintain muscle mass despite dystrophin deficiency, we measured protein turnover rates in muscles of mdx and wild-type (C57BL/10) mice in vivo. At all ages studied, rates of muscle protein synthesis and degradation were higher in mdx than in C57BL/10 mice.

Aging↗
PubMed1990

Mast cells in neuromuscular diseases.

The lectin Dolichos biflorus agglutinin has been used to identify mast cells in normal skeletal muscle and to investigate changes in their number in a wide range of human neuromuscular diseases and in rat muscle damaged by the local anaesthetic bupivacaine. Few mast cells were found in the perimysium of normal skeletal muscle but numbers were increased in human muscle biopsies which showed necrosis and regeneration of fibrosis. In bupivacaine-induced muscle damage, increased mast cell counts occurred during the necrotic phase and particularly during the phase of active regeneration. In addition, increased numbers of mast cells were observed in the underlying histologically normal muscle. These results show that mast cells are influenced by pathological changes in skeletal muscle and, in view of the known functions of mast cells in other tissues, it is possible that they are capable of modulating disease processes in muscle.

Animals↗
PubMed1990

The assessment of treatment response in non-Hodgkin's lymphoma by image guided 31P magnetic resonance spectroscopy.

Serial image guided 31P magnetic resonance spectroscopy (MRS) studies were performed in eight patients with non-Hodgkin's lymphoma to determine the changes in phosphorus metabolites that occur in vivo in response to chemotherapy. Pre-treatment spectral characteristics were different in high and low grade lymphoma. A larger inorganic phosphate (Pi) peak was seen in high grade NHL relative to phosphomonoesters (PME) or beta adenosine triphosphate (beta ATP), producing significant differences in the PME/Pi and Pi/beta ATP metabolite ratios, and probably reflecting a larger hypoxic cell fraction within the high grade lymphomas. Consistent metabolite changes were seen with treatment, and before reductions in tumour bulk had occurred. Alterations in tumour energetics with changes in Pi and beta ATP, and increases in phospholipid turnover reflected as an increase in the phosphodiester (PDE) resonance were detected. Changes were seen between days 10 and 27 in low grade lymphoma treated with oral alkylating therapy and between days 1 and 5 in lymphoma treated with intensive combination chemotherapy. Increases in the PDE/beta ATP metabolite ratio may be an early indicator of response to chemotherapy in human tumours. These studies illustrate the feasibility and clinical potential of image guided 31P MRS as a means of assessing response to therapy.

Adenosine Triphosphate↗