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Biomedical subjects

M B Davies

Publications and source records attributed to M B Davies.

At least 19 recordsLinked to original sources
PubMed2005

An origin for short gamma-ray bursts unassociated with current star formation.

Two short (< 2 s) gamma-ray bursts (GRBs) have recently been localized and fading afterglow counterparts detected. The combination of these two results left unclear the nature of the host galaxies of the bursts, because one was a star-forming dwarf, while the other was probably an elliptical galaxy. Here we report the X-ray localization of a short burst (GRB 050724) with unusual gamma-ray and X-ray properties. The X-ray afterglow lies off the centre of an elliptical galaxy at a redshift of z = 0.258 (ref. 5), coincident with the position determined by ground-based optical and radio observations. The low level of star formation typical for elliptical galaxies makes it unlikely that the burst originated in a supernova explosion. A supernova origin was also ruled out for GRB 050709 (refs 3, 31), even though that burst took place in a galaxy with current star formation. The isotropic energy for the short bursts is 2-3 orders of magnitude lower than that for the long bursts. Our results therefore suggest that an alternative source of bursts--the coalescence of binary systems of neutron stars or a neutron star-black hole pair--are the progenitors of short bursts.

Journal Article↗
PubMed2005

Gross anatomy of the interphalangeal joint of the great toe: implications for excision of plantar capsular accessory ossicles.

Bony or cartilaginous ossicles occur at the plantar aspect of the interphalangeal joint of the great toe. The variation in pattern, prevalence, and anatomic relationships of these structures is not clearly established in the literature, especially in a Caucasian population. Without this knowledge, pathology at this joint may be underestimated and surgical approaches may be poorly planned particularly as radiographs underestimate the incidence of ossicles at this joint. The aims of this study were to determine the incidence and pattern of ossicles at this joint and to establish their anatomic relationships to aid planning the approach for their excision. The interphalangeal joint of the left hallux was dissected in 40 British Caucasian cadavers and the pattern of nodules and their anatomic relationships were established. In 27.5% of subjects, there was no identifiable ossicle and, in these specimens, the tendon of flexor hallucis longus was adherent to the joint capsule. In the remaining specimens (72.5%), a bursa separated the tendon of flexor hallucis longus from the plantar joint capsule and nodules were found embedded within the joint capsule. More than half (52.5%) of the specimens had a single nodule located centrally within the plantar capsule and the remaining 20% had two nodules lying within the capsule. This study shows that a large proportion of the population have either one or two bony or cartilaginous ossicles at this joint. It has also shown that, when present, these structures do not lie within the tendon of flexor hallucis longus and may be most safely excised from a medial approach.

Adult↗
PubMed2003

Determination of trace concentrations of dissolved nitric oxide in a biological buffer.

A new real-time method for measuring a trace concentration of nitric oxide (NO) in a complex matrix routinely used in pharmacological studies of its bioactivity is described. NO was quantified as a gas by chemiluminescence after extraction from a continuous liquid sample flow with a limit of detection of 0.042 nmol dm(-3) at a signal to noise ratio of 3. Theories to calculate the concentration of NO in the liquid sample flow from a direct measurement of NO in the extraction carrier gas are presented. The efficiency of extraction is determined by a stopflow experiment. An example is presented of the measurement of the steady-state concentrations of NO in Krebs-bicarbonate buffer at pH 7.4 and 37 degrees C when its liquid surface is sequentially exposed to gases containing various concentrations of NO in O2 plus CO2.

Flow Injection Analysis↗
PubMed2003

Interphalangeal sesamoid bones of the great toe: an anatomic variant demanding careful scrutiny of radiographs.

We describe a patient who was found to have two sesamoid bones at the interphalangeal joint of the right great toe after radiographs for dislocation of the joint. Recognition of the sesamoids required careful scrutiny of the films. Interphalangeal sesamoids may cause painful callosities plantar to the joint or may become incarcerated in a dislocated joint. Our patient made a good recovery. The presence of sesamoid bones on the medial and lateral sides of the joint was unusual.

Adult↗
PubMed2002

Interleukin 1 genotypes in multiple sclerosis and relationship to disease severity.

We studied the association between clinical outcome in MS and allelic variants single nucleotide polymorphisms (SNPs) of interleukin-1alpha (IL-1alpha), IL-1beta and a variable number tandem repeat (VNTR) in IL-1 receptor antagonist (IL-1RN). A total of 377 patients with MS were studied. Significant associations between IL-1 genotypes and clinical outcome were found using logistic regression after correction for gender, onset age and disease duration. The same trends were subsequently demonstrated in a second independent group of 67 primary progressive patients. Our results suggest that genetically determined immunomodulation mediated by IL-1 influences long-term prognosis in multiple sclerosis (MS).

Adjuvants, Immunologic↗
PubMed2002

Circulating nitrite anions are a directly acting vasodilator and are donors for nitric oxide.

Inhaled nitric oxide (NO) is a pulmonary vasodilator, but also acts systemically, causing negative cardiac inotropic effects and a fall in systemic vascular resistance. Circulating metabolites of NO are presumed to be responsible. We questioned the role of nitrite anions and the manner in which they might contribute to these effects. Nitrite and nitrate anions coexist in blood, while circulating levels of dissolved NO are very low. Nitrate anions are not biologically active, but nitrite anions may have a biological role through the release of NO. In vitro, at 37 degrees C and in aerated Krebs bicarbonate solution, the steady-state concentration of dissolved NO was proportional to the concentration of NO in the gas. Nanomolar concentrations of dissolved NO coexisted with micromolar concentrations of nitrite anions. The idea of an equilibrium between the two in solution was also supported by the observed release of NO from nitrite anions in the absence of gas. With rings of precontracted pig pulmonary arteries (prostaglandin F(2alpha); 10 micromol/l), the steady-state concentration of dissolved NO causing 50% relaxation (EC(50)) was 0.84+/-0.25 nmol/l, corresponding to a gaseous concentration of 2.2 p.p.m. The EC(50) of nitrite was 4.5+/-0.7 micromol/l, a concentration normally found in plasma. The estimated concentration of dissolved NO derived from this nitrite was 4.5 pmol/l, some 100 times lower than would be needed to cause relaxation. The rate of exhalation of NO was increased and pulmonary vascular resistance was reduced by the addition of nitrite solution to the perfusate of isolated perfused and ventilated pig lungs, but only when millimolar concentrations were achieved. Thus circulating nitrite anions are a direct vasodilator, only being a carrier of effective amounts of "free" NO at higher than physiological concentrations.

Analog-Digital Conversion↗
PubMed2001

HLA-DRB1 and disease outcome in multiple sclerosis.

The association between susceptibility to multiple sclerosis (MS) and the class II MHC allele HLA-DRB1*15 is well established although a possible relationship between this allele and outcome in MS is less clear. HLA-DRB1 typing was performed on 375 unrelated white patients with clinically definite MS and on 367 healthy controls. Putative associations of the gene with outcome were examined by dividing patients into two groups: those with an EDSS of 0-5.5 (mild/moderate disease) and those with an EDSS of 6-10 (severe disease). In order to minimise the effects of disease variability patients with a disease duration of at least 10 years or 15 years were examined. As subsidiary HLA-DRB1*03 and HLA-DRB1*04 associations have been previously reported, the effect of these alleles was also examined. As expected, HLA-DRB1*15 was found more frequently in patients than in controls (P < 0.000001). HLA-DRB1*15 positive patients had a significantly earlier age at onset than HLA-DRB1*15 negative patients. No significant associations were noted between HLA-DRB1*15 and outcome in the total patient group or in patients with a disease duration of 10 years or longer. In patients with a disease duration of at least 15 years HLA-DRB1*15 negative status was associated with a worse prognosis, although this did not remain significant after correction for multiple testing. It is thus likely that the contribution of HLA in MS is primarily towards onset and initial triggering mechanisms rather than influencing disease progression, chronicity and severity.

Adult↗
PubMed2000

Glutathione S-transferase polymorphisms in MS: their relationship to disability.

BACKGROUND: Oxidative stress has been implicated in inflammatory demyelination. The glutathione S-transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress. Certain GST loci are polymorphic, demonstrating alleles that are null (GSTM1/GSTT1), encode low activity variants (GSTP1), or are associated with variable inducibility (GSTM3). OBJECTIVES: To investigate the association between clinical outcome in MS and allelic variants of GSTM1, GSTM3, GSTT1, and GSTP1. METHODS: Four hundred patients with clinically definite MS were studied. Disability was measured using the Kurtzke Expanded Disability Status Scale (EDSS). Disability was graded as mild (EDSS 0-4), moderate (4.5-5.5), or severe (EDSS 6-10). PCR-based genotyping was performed using DNA extracted from lymphocytes. Significant associations between GST genotypes and clinical outcome were corrected for gender, onset age, and disease duration using logistic regression. RESULTS: We found that the GSTM3 AA genotype was associated with severe disability in patients with a disease duration of more than 10 years (p = 0.027, n = 177, OR = 2.4, 95% CI = 1.1-5.0). Homozygosity for both GSTM1*0 and GSTP1*Ile105 containing allele was associated with severe disability in patients with a disease duration greater than 10 years (p = 0.022, n = 179, OR = 5.0, 95% CI = 1.3-19.8). CONCLUSIONS: Our results suggest that long-term prognosis in MS is influenced by a genetically determined ability to remove the toxic products of oxidative stress.

Adult↗
PubMed2000

Correlation of MRI lesions with visual psychophysical deficit in secondary progressive multiple sclerosis.

The aim of this work was, first, to clarify the nature of the relationship between the sensory deficit in the demyelinated visual pathway and morphological changes revealed by MRI and, secondly, to test whether there was a preferential effect of demyelination for either the magnocellular or parvocellular pathway in established multiple sclerosis. Twenty-four patients with secondary progressive multiple sclerosis were studied psychophysically and by MRI of the optic nerve and brain. MRI was performed with a Phillips (0.5T) scanner. Visual pathway MRI lesion load was evaluated independently using the total optic nerve lesion length and lesion area seen on STIR (short inversion time inversion recovery) images of the optic nerve and the total post-chiasmal lesion area on T(1)-, T(2)- and proton-density-weighted images of the brain. Psychophysical tests determined 75%-seeing thresholds for horizontal gratings consisting of isoluminant red and green sinusoids of the same spatial frequency combined out-of-phase for preferential stimulation of the parvocellular system and in-phase for preferential stimulation of the magnocellular system. It was found that, in this group of patients, visual psychophysical loss was significantly correlated with lesion area seen on proton density MRI sequences of the post-chiasmal visual pathway, and that the parvocellular pathway was more affected than the magnocellular pathway, especially at lower spatial frequencies.

Adolescent↗
PubMed2000

Polymorphisms of apolipoprotein E; outcome and susceptibility in multiple sclerosis.

Allelic variants of the apolipoprotein E (APOE) gene influence the course of several neurological diseases. In multiple sclerosis the concentration of APOE in cerebrospinal fluid and its intrathecal synthesis is reduced. Specific isoforms of APOE may also be important and it has been suggested that possession of the epsilon4 allele may be associated with a more aggressive disease process. These data prompted us to re-examine, in a large group of patients with multiple sclerosis, the proposal that allelism in the apolipoprotein gene influences disease course. Genotypes were determined in a well-defined group of 370 unrelated Caucasians with clinically definite multiple sclerosis and in 159 healthy controls. Age at onset, sex, disease duration, disease subtype were recorded. Disability was measured using the Kurtzke expanded disability status score in patients with a disease duration of 10 years or greater. There was no significant difference in APOE allele or genotype frequencies between patients and controls, between disease subtypes or between genders. APOE genotype did not significantly influence age of onset, and no significant relationship between genotype, allele frequency and disease severity was found. This study suggests that individual APOE alleles or genotypes do not determine disease susceptibility or the clinical course of multiple sclerosis.

Adult↗
PubMed1998

MRI of optic nerve and postchiasmal visual pathways and visual evoked potentials in secondary progressive multiple sclerosis.

We studied the relationship between abnormalities shown by MRI and functional disturbances in the visual pathway as assessed by the visual evoked potential (VEP) in 25 patients with established multiple sclerosis (MS); only 4 of whom had a history of acute optic neuritis. Optic nerve MRI was abnormal in 19 (76%) and is thus useful in detecting subclinical disease. Optic nerve total lesion length and area on the STIR sequence was found to correlate significantly with prolongation of the VEP latency. This may reflect a predominantly demyelinating rather than inflammatory origin for the signal change in the optic nerve.

Adult↗