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Biomedical subjects

E Dawson

Publications and source records attributed to E Dawson.

At least 19 recordsLinked to original sources
PubMed2003

Arm blood flow and oxygenation on the transition from arm to combined arm and leg exercise in humans.

The cardiovascular response to exercise with several groups of skeletal muscle implies that work with the legs may reduce arm blood flow. This study followed arm blood flow (Yarm) and oxygenation on the transition from arm cranking (A) to combined arm and leg exercise (A+L). Seven healthy male subjects performed A at approximately 80 % of maximum work rate (Wmax) and A at ~80 % Wmax combined with L at approximately 60 % Wmax. A transition trial to volitional exhaustion was performed where L was added after 2 min of A. The Yarm was determined by constant infusion thermodilution in the axillary vein and changes in biceps muscle oxygenation were measured with near-infrared spectroscopy. During A+L Yarm was lowered by 0.38 +/- 0.06 l min-1 (10.4 +/- 3.3 %, P < 0.05) from 2.96 +/- 1.54 l min-1 during A. Total (HbT) and oxygenated haemoglobin (HbO2) concentrations were also lower. During the transition from A to A+L Yarm decreased by 0.22 +/- 0.03 l min-1 (7.9 +/- 1.8 %, P < 0.05) within 9.6 +/- 0.2 s, while HbT and HbO2 decreased similarly within 30 +/- 2 s. At the same time mean arterial pressure and arm vascular conductance also decreased. The data demonstrate reduction in blood flow to active skeletal muscle during maximal whole body exercise to a degree that arm oxygen uptake and muscle tissue oxygenation are compromised.

Adult↗
PubMed2003

beta-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation.

We have mapped and sequenced both chromosome breakpoints of a balanced t(6;11)(q14.2;q25) chromosome translocation that segregates with a schizophrenia-like psychosis. Bioinformatics analysis of the regions revealed a number of confirmed and predicted transcripts. No confirmed transcripts are disrupted by either breakpoint. The chromosome 6 breakpoint region is gene poor, the closest transcript being the serotonin receptor 1E (HTR1E) at 625 kb telomeric to the breakpoint. The chromosome 11 breakpoint is situated close to the telomere. The closest gene, beta-1,3-glucuronyltransferase (B3GAT1 or GlcAT-P), is 299 kb centromeric to the breakpoint. B3GAT1 is the key enzyme during the biosynthesis of the carbohydrate epitope HNK-1, which is present on a number of cell adhesion molecules important in neurodevelopment. Mice deleted for the B3GAT1 gene show defects in hippocampal long-term potentiation and in spatial memory formation. We propose that the translocation causes a positional effect on B3GAT1, affecting expression levels and making it a plausible candidate for the psychosis found in this family. More generally, regions close to telomeres are highly polymorphic in both sequence and length in the general population and several studies have implicated subtelomeric deletions as a common cause of idiopathic mental retardation. This leads us to the hypothesis that polymorphic or other variation of the 11q telomere may affect the activity of B3GAT1 and be a risk factor for schizophrenia and related psychoses in the general population.

Base Sequence↗
PubMed2003

Cardiac troponin T in female athletes during a two-day mountain marathon.

BACKGROUND: Equivocal studies exist on the potential of cardiac damage following prolonged endurance exercise. AIMS: The aim of the study was to examine humoral markers of cardiac damage in female athletes during a 2-day mountain endurance race. METHODS: Venous blood samples were drawn from seven female competitors prior to, and immediately following day-1 and day-2 of the event. The serum was analysed for total creatine kinase (CK), creatine kinase isoenzyme MB (CKMB), and cardiac troponin T (cTnT). RESULTS: Elevations in CK and CKMB were apparent following day-1 of the event (mean +/- SD; CK 84.1 +/- 54.6 mg/L vs. 387 +/- 276.7 mg/L, CKMB 2 +/- 1.7 mg/L vs. 5.9 +/- 1.7 mg/L) and subsequently rose further following race completion (CK 743 +/- 500 mg/L, CKMB 11.9 +/- 4.9 mg/L). Elevations in cTnT were noted in three competitors following day-1 cTNT (range 0.013-0.044 mg/L) and remained elevated in two competitors following day-2 (range 0.014-0.017 mg/L). CONCLUSIONS: The elevations in cTnT likely represent release from the cytosolic fraction. The mechanism responsible for such release is yet to be elucidated.

Adult↗
PubMed2002

Evidence of exercise-induced cardiac dysfunction and elevated cTnT in separate cohorts competing in an ultra-endurance mountain marathon race.

Cardiac damage has recently been implicated in the aetiology of "exercise induced cardiac dysfunction". The humoral markers of cardiac damage that have been utilised to date are not sufficiently cardio-specific to investigate this hypothesis. The aim of the present study was to examine cardiac function following prolonged exercise, and investigate the contention of cardiac damage utilising a new highly cardio-specific marker. Thirty-seven competitors in the 2-day Lowe Alpine Mountain Marathon 2000 volunteered for the study. Competitors were sub-divided into 2 groups. Group 1 (n = 11) were examined using echocardiography pre and post the event, examining left ventricular diastolic and systolic function. Group 2 (n = 26) had venous blood samples drawn prior to the event and immediately following day-1 and day-2. Blood samples were analysed for total creatine kinase activity (CK), creatine kinase isoenzyme MB(mass) (CK-MB(mass)), and cardiac troponin T. Echocardiographic results indicated left ventricular diastolic and systolic dysfunction following cessation of exercise. CK and CK-MB(mass) were both elevated following day-1, and immediately following race completion. Cardiac troponin T levels were below the 99th percentile (0.01 microg/L) in all subjects prior to the event, following day-1 cTnT was elevated above 0.01 microg/L in 13 subjects, but returned to below 0.01 microg/L following race completion on day-2. However, no individual data reached clinical cut-off levels for acute myocardial infarction (AMI) (0.1 microg/L). Two days arduous exercise over mountainous terrain resulted in cardiac dysfunction, and significant skeletal muscular degradation. The elevation of cTnT above the 99th percentile in the present study is suggestive of minimal myocardial damage. The clinical significance of and exact mechanism responsible for such damage remains to be elucidated.

Adult↗
PubMed2001

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Chromosomes, Human, Pair 1↗
PubMed2001

Active management in patients with ocular manifestations of myasthenia gravis.

PURPOSE: Myasthenia gravis can cause variable strabismus with disabling diplopia and/or poor cosmesis. A retrospective study of a group of patients with myasthenia gravis or 'myasthenia gravis like' syndromes was made. METHODS: The study group consisted of patients who had undergone botulinum toxin treatment and/or surgery for disabling diplopia, poor cosmesis or both. Surgical treatment was by conventional techniques including recess/resect, posterior fixation, superior oblique tenotomy and adjustable sutures. RESULTS: There were 9 patients in the study group (8 female, 1 male). Age at surgery ranged from 21 to 59 years (mean 46 years). Six were symptom-free following treatment. Two, although symptomatically improved, had occasional diplopia. One patient failed treatment and required an occlusive contact lens. CONCLUSIONS: The ocular manifestations of myasthenia gravis or 'myasthenia gravis like' syndromes may respond to surgery and/or botulinum toxin injection. Active intervention should be considered when deviations become stable. To our knowledge this is the first report of the use of botulinum toxin in such patients.

Adolescent↗
PubMed2001

Botulinum toxin to the lateral rectus for the treatment of esotropia with paradoxical diplopia.

A retrospective review of six patients with paradoxical diplopia in the presence of esotropia was carried out. All patients were treated with botulinum toxin to the lateral rectus of the affected side. Five patients had no diplopia post toxin and the remaining patient had diplopia which could be ignored. The number of injections per patient ranged between 3 and 34. Three patients went on to have surgery to increase the angle of esotropia, with relief of diplopia. We conclude that botulinum toxin has a role in the treatment of esotropic patients with paradoxical diplopia.

Adolescent↗
PubMed2001

Squint surgery in the over sixties.

We examined the indications for strabismus surgery in patients 60 years of age or older. A retrospective review was carried out of 111 case records of such patients operated on between January 1992 and May 1999. There were 59 females and 52 males, ranging in from 60 to 90 years (mean 67.3 years). The diagnoses were varied: the largest groups were cranial nerve palsies and consecutive strabismus. Fifty-six patients demonstrated binocular potential pre-operatively and 60 post-operatively. Twenty-three patients underwent reoperation. Twenty-eight patients also received botulinum toxin. The mean follow-up was 15 months, 54 patients were discharged within 6 months. Elective strabismus surgery in this age group constituted 7% of strabismus surgery activity (single surgeon). There were no complications. There is a demand for strabismus surgery in this ever increasing age group.

Aged↗
PubMed2001

Adjustable squint surgery in children.

The adjustable suture technique in adult strabismus surgery is well established. The aim of this study was to assess its feasibilty/outcome in a younger age group. A retrospective review of 359 case notes of patients, under the age of 16 years, who underwent squint surgery between 1992 and 1999 was carried out. Of these, 45 (13%) had undergone surgery with the adjustable suture technique. Post-operatively, 34 patients achieved an angle of +/- 10 pd and required no further treatment. We sought co-operation from the parents and encouraged their active participation during adjustment. It was not necessary for any child to return to the operating theatre to finalise adjustment. We conclude that this is an effective treatment in motivated children, as 76% (34/45) obtained an excellent result.

Adolescent↗
PubMed2001

A SNP resource for human chromosome 22: extracting dense clusters of SNPs from the genomic sequence.

The recent publication of the complete sequence of human chromosome 22 provides a platform from which to investigate genomic sequence variation. We report the identification and characterization of 12,267 potential variants (SNPs and other small insertions/deletions) of human chromosome 22, discovered in the overlaps of 460 clones used for the chromosome sequencing. We found, on average, 1 potential variant every 1.07 kb and approximately 18% of the potential variants involve insertions/deletions. The SNPs have been positioned both relative to each other, and to genes, predicted genes, repeat sequences, other genetic markers, and the 2730 SNPs previously identified on the chromosome. A subset of the SNPs were verified experimentally using either PCR-RFLP or genomic Invader assays. These experiments confirmed 92% of the potential variants in a panel of 92 individuals. [Details of the SNPs and RFLP assays can be found at http://www.sanger.ac.uk and in dbSNP.]

Base Composition↗
PubMed2001

A cardiac prevention and rehabilitation programme for all patients at first presentation with coronary artery disease.

OBJECTIVE: To develop and test a cardiac prevention and rehabilitation programme for achieving sustained lifestyle, risk factor, and therapeutic targets in patients presenting for the first time with exertional angina, acute coronary syndromes, or coronary revascularisation. DESIGN: A descriptive study. SETTING: A hospital based 12 week outpatient programme. INTERVENTIONS: A multiprofessional family based programme of lifestyle and risk factor modification. MAIN OUTCOME MEASURES: Non-smoking status, body mass index, blood pressure, plasma cholesterol, use of prophylactic drugs. RESULTS: 158 patients (82% of 194 possible cases) were recruited over 15 months, with 72% completing the programme. Targets for achieving non-smoking status, blood pressure < 140/90 mm Hg, and total cholesterol < 4.8 mmol/l were achieved in 92%, 73%, and 62%, respectively, and the proportion on aspirin, beta blockers, and lipid lowering treatment was 95%, 58%, and 64% on referral back to general practice for continuing care. CONCLUSIONS: A comprehensive cardiac prevention and rehabilitation programme can be offered to all patients presenting for the first time with coronary heart disease, including those with exertional angina who are normally managed in primary care. Lifestyle, risk factor, and therapeutic targets can be successfully achieved in most patients with such a hospital based programme.

Adult↗
PubMed2001

Increased binocular enhancement of contrast sensitivity and reduced stereoacuity in Duane syndrome.

PURPOSE: To compare the binocular enhancement of contrast sensitivity and stereoacuity in patients with Duane syndrome and normal subjects. METHODS: Monocular and binocular contrast sensitivity functions were determined using a two-alternative, forced-choice method in 14 patients with Duane syndrome and 14 normal subjects. Monocular and binocular log minimum angle of resolution (logMAR) acuities were measured, and stereoacuity was determined using the Titmus and TNO stereotests. RESULTS: In the patients with Duane syndrome, the binocular enhancement of contrast sensitivity was increased across all spatial frequencies, although stereoacuity was reduced compared to that of the normal subjects. The increased enhancement was caused by a reduction in monocular contrast sensitivity rather than an increase in binocular contrast sensitivity. The patients with Duane syndrome also showed a generalized reduction of contrast sensitivity at high spatial frequencies. CONCLUSIONS: It is suggested that the combination of reduced stereoacuity and increased binocular enhancement of contrast sensitivity seen in Duane syndrome can be explained by a partial loss of binocular cortical cells, caused by intermittent misalignment of the eyes during early visual development.

Adolescent↗
PubMed2000

The extent of linkage disequilibrium in four populations with distinct demographic histories.

The design and feasibility of whole-genome-association studies are critically dependent on the extent of linkage disequilibrium (LD) between markers. Although there has been extensive theoretical discussion of this, few empirical data exist. The authors have determined the extent of LD among 38 biallelic markers with minor allele frequencies >.1, since these are most comparable to the common disease-susceptibility polymorphisms that association studies aim to detect. The markers come from three chromosomal regions-1,335 kb on chromosome 13q12-13, 380 kb on chromosome 19q13.2, and 120 kb on chromosome 22q13.3-which have been extensively mapped. These markers were examined in approximately 1,600 individuals from four populations, all of European origin but with different demographic histories; Afrikaners, Ashkenazim, Finns, and East Anglian British. There are few differences, either in allele frequencies or in LD, among the populations studied. A similar inverse relationship was found between LD and distance in each genomic region and in each population. Mean D' is.68 for marker pairs <5 kb apart and is.24 for pairs separated by 10-20 kb, and the level of LD is not different from that seen in unlinked marker pairs separated by >500 kb. However, only 50% of marker pairs at distances <5 kb display sufficient LD (delta>.3) to be useful in association studies. Results of the present study, if representative of the whole genome, suggest that a whole-genome scan searching for common disease-susceptibility alleles would require markers spaced < or = 5 kb apart.

Africa↗
PubMed2000

An SNP map of human chromosome 22.

The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.

Cell Line↗
PubMed2000

Refinement of an ovarian cancer tumour suppressor gene locus on chromosome arm 22q and mutation analysis of CYP2D6, SREBP2 and NAGA.

Loss of heterozygosity on chromosome 22q was detected in 53% of 123 ovarian carcinomas, suggesting the presence of at least one tumour suppressor gene. We have refined the location of one possible tumour suppressor gene to the region between the microsatellite markers D22S299 and CYP2D. Located within this region are the genes SREBP2 (sterol regulatory element binding protein 2) and NAGA (N-acetyl-alpha-D-galactosaminidase). Investigation of the coding exons of these genes by single stranded conformational polymorphism/heteroduplex analysis failed to identify any somatic genetic alterations in 57 ovarian tumours which exhibited LOH on 22q13. The CYP2D gene locus straddles the distal boundary of the candidate region. Germline variants of the active CYP2D6 gene with differing abilities to metabolise specific substrates have been implicated in the development of various cancers. Comparison of the frequency of the two common germline mutations among 258 ovarian tumours and 231 non-cancer controls did not reveal any significant differences between the two groups. This suggests that the known polymorphic variants of CYP2D6 are not involved in ovarian cancer predisposition. We also conclude that neither NAGA nor SREBP2 are likely to be mutated in ovarian carcinomas.

Chromosome Mapping↗