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Biomedical subjects

C A Graham

Publications and source records attributed to C A Graham.

At least 19 recordsLinked to original sources
PubMed1999

Lack of association of transforming growth factor (TGF)-beta 1 and beta 2 gene polymorphisms with multiple sclerosis (MS) in Northern Ireland.

OBJECTIVE: To examine the influence of TGF-beta genes on MS susceptibility. BACKGROUND: TGF-beta, of which three homologous isoforms exist (1, 2 and 3), is a strongly immunosuppressive cytokine-inhibiting expression of pro-inflammatory cytokines and blocking cytokine induction of adhesion molecules. TGF-beta delays onset of EAE and TGF-beta 1 gene knockout mice develop fatal multifocal inflammatory disease. High TGF-beta levels exist during MS remission whilst E-selectin, whose expression is inhibited by TGF-beta, is found at higher levels in primary progressive disease (PPMS) and it is postulated that the unremitting course of PPMS may be due to low levels of TGF-beta. METHODS: Gene association studies using separate polymorphic microsatellite markers for TGF-beta 1 and TGF-beta 2 were performed, incorporating 151 relapsing-remitting or secondary progressive MS (RR/SPMS) patients, 104 PPMS patients and 159 normal controls (Nor). Forward primers were 5' end-labelled with 6-Fam, PCR products were analysed on an Applied Biosystems 373A fluorescent fragment analyser and Genescan 672 software was used for allele sizing. RESULTS: No significant differences existed in allele frequencies between either MS group and controls regarding the TGF-beta 1 marker: RR/SPMS vs Nor (P = 0.48, df = 8); PPMS vs Nor (P = 0.34, df = 8). Similarly there were no associations demonstrated with the TGF-beta 2 marker: RR/SPMS vs Nor (P = 0.24, df = 2); PPMS vs Nor (P = 0.53, df = 2). CONCLUSION: These data indicate that TGF-beta 1 and beta 2 genes are not loci influencing MS susceptibility, either RR/SPMS or PPMS, in this population.

Alleles↗
PubMed1998

Genotype/phenotype correlations in familial hypercholesterolaemia.

It is now possible to identify the specific gene defect in the majority of patients with familial hypercholesterolaemia. A potential benefit of this knowledge, in addition to helping with family screens, is to be able to predict the future clinical course. In order to do this, detailed genotype/phenotype correlation studies are required.

Apolipoproteins B↗
PubMed1998

Restricting extensions to permitted licensing hours does not influence the numbers of alcohol or assault related attendances at an inner city accident and emergency department.

OBJECTIVE: To determine the effect of restricting extensions to permitted licensing hours on the numbers of alcohol or assault related attendances at an inner city accident and emergency (A&E) department. METHODS: Prospective data collection on consecutive attendances between 17.00 and 09.00 h during three study periods: two weeks before the introduction of the restriction, two weeks immediately afterwards, and for a two week period beginning five weeks after the change. Blood alcohol concentration was measured with a pocket alcohol meter. RESULTS: Overall 56.5% of patients (n = 2836) provided a breath sample, and 28.9% (819) were positive. The proportion of patients testing positively peaked between 02.00 and 04.00 h. A very high proportion of assault cases who were tested (260) were positive (67.3%). Assault cases comprised 19.1% of all attendances between 24.00 and 04.00 h. No significant changes in the pattern of alcohol or assault related attendances followed the restriction in extensions to permitted licensing hours. CONCLUSIONS: A policy of uniform closing times of licensed premises does not influence the profile of alcohol or assault related attendances at an inner city A&E department.

Alcohol Drinking↗
PubMed1997

Tumour necrosis factor microsatellites show association with multiple sclerosis.

The TNF alpha and beta genes are located between the class I and class III HLA loci and have been implicated in the pathogenesis of multiple sclerosis. We carried out allelic association analysis using four microsatellite markers localised within a 20 kb region around the TNF genes. The study was performed on DNA samples from 189 clinically definite MS patients and 206 normal controls, all of Northern Irish origin. The allele distributions for the TNFa and b markers were significantly different between the MS patients and controls (P = 0.014, df 8 and 0.0019, df 4, respectively). The difference could largely be attributed to increases in the TNFa 118 bp allele and the TNFb 127 bp allele in MS patients, with a conserved MS associated haplotype (130:118:127 TNF d:a:b). Of the 19 patients homozygous for this haplotype, 17 were HLA typed and results suggested that the TNF haplotype association can occur independently of inheritance of DR2. Transmission disequilibrium testing (TDT) also supported the TNFa 118 bp association. These results suggest that in this population TNF is possibly one of the genetic factors contributing to MS susceptibility.

Alleles↗
PubMed1997

Anaesthesia for the management of distal radius fractures in adults in Scottish hospitals.

The objective of this study was to determine the methods of anaesthesia used for the reduction of distal radius fractures in adults in Scotland and to compare this with the UK situation. The method used was a telephone questionnaire of accident and emergency doctors in 25 Scottish hospitals dealing with trauma. Thirty-two per cent still use general anaesthesia routinely for these procedures despite its cost, complexity and need for admission in the majority of cases. Forty-four per cent now use the Bier's block technique of regional anaesthesia, with the attendant advantages of ease of use, rapid recovery and no need for admission in the majority of patients. Twelve per cent use intravenous sedation and 12% use haematoma blocks for manipulations. It is concluded that Bier's block may be the anaesthetic method of choice for the management of distal radius fractures both in efficiency and economic terms in Scotland. However, training for Bier's blocks needs to be standardized and improved.

Adult↗
PubMed1997

Prehospital emergency rapid sequence induction of anaesthesia.

OBJECTIVE: To determine the number of and reasons for rapid sequence inductions done by accident and emergency (A&E) doctors out of hospital as part of the activities of the MEDIC 1 Flying Squad. "Rapid sequence induction" was defined as any attempted endotracheal intubation accompanied by use of drugs to assist intubation and ventilation, including opiates, benzodiazepines, intravenous and topical anaesthetics, and neuromuscular blocking drugs. METHODS: Retrospective study of all MEDIC 1 and A&E records over the period 1 February 1993 to 28 February 1996 (37 months). The anaesthetic technique used, drugs used, complications, difficulties, reasons for induction out of hospital, and grade of doctor performing the technique were determined. RESULTS: Various anaesthetic techniques were used to secure the airway definitively by endotracheal intubation. Several difficulties were encountered in the prehospital setting, all of which were dealt with successfully. CONCLUSIONS: The lack of complications related to rapid sequence induction in prehospital care suggests that this technique is safe when done by A&E doctors on appropriate patients.

Anesthesia↗
PubMed1997

APO E genotype and familial hypercholesterolaemia.

Apolipoprotein E genotypes were measured in 83 patients with familial hypercholesterolaemia (FH) and in 175 blood donor controls. Following DNA extraction from peripheral blood, each sample was genotyped for the Apo E polymorphism by polymerase chain reaction. No significant differences were found in the levels of the epsilon 2 and epsilon 3 alleles between the two groups, while the epsilon 4 allele was approximately twice as prevalent in the FH patients as in controls (P = 0.006, df = 1). Of the FH patients, 8.4% were homozygous for the epsilon 4 allele while this genotype was rare in controls (P = 0.009, df = 1). These results suggest that the epsilon 4 allele is over represented in the FH population and may contribute to increased cholesterol levels and consequent vascular disease.

Adolescent↗
PubMed1996

Mutation characterization of CFTR gene in 206 Northern Irish CF families: thirty mutations, including two novel, account for approximately 94% of CF chromosomes.

A variety of mutation detection techniques, including restriction endonuclease digestion, allele specific oligonucleotides, and automated fluorescent sequencing, were used in the identification of 15 CFTR mutations representing 86.7% of CF chromosomes in 206 Northern Irish cystic fibrosis (CF) families. A systematic analysis of the 27 exons and intron/exon boundaries of the CFTR gene was performed using denaturing gradient gel electrophoresis (DGGE) in an attempt to characterise the 55 unknown CF mutations in 51 patients. Twenty different mutations were detected by DGGE on 30 chromosomes accounting for a further 7.3% of CF alleles. Fifteen of these mutations had not previously been found in Northern Ireland, and two are novel, M1I(G > T) and V562L. In total, 30 CFTR mutations account for 93.9% of the 412 Northern Irish CF chromosomes tested. The three major CF mutations in Northern Ireland are delta F508, G551D, and R117H with respective frequencies of 68.0%, 5.1%, and 4.1%. The efficacy of the DGGE technique was proven by the detection of 77 out of 77 control variants from all the CFTR exons. DGGE is a highly efficient and sensitive method for mutation screening especially in large genes where the mutation spectrum is known to be heterogeneous.

Alleles↗
PubMed1996

A novel single base deletion in the LDLR gene (211delG): Effect on serum lipid profiles and the influence of other genetic polymorphisms in the ACE, APOE and APOB genes.

A single base deletion (211delG) in the low density lipoprotein receptor (LDLR) gene was shown to cause familial hypercholesterolaemia (FH) in a large family from Northern Ireland. Twenty-four of 52 family members tested had this mutation, 13 of which were newly diagnosed. Mutation-positive individuals had significantly higher mean total-cholesterol (TC) and LDL-cholesterol (LDL-C) than those without 211delG. LDL-C was a more accurate indicator of disease status than TC. When TC levels alone were considered, in individuals over 16 years, a false negative rate (TC < 7.5 mmol/l) of 40% was found; however this fell to 13% based on inclusion of LDL-C levels. Individuals with coronary artery disease (CAD) had significantly higher TC levels than those without CAD and tended to have tendinous xanthomas (TX) and corneal arcus (CA). Generic polymorphisms in the angiotensin converting enzyme (ACE) and apolipoprotein (apo) B genes did not appear to be associated with lipid levels or with the clinical severity of the disease; however, the apo E epsilon4 allele did show a lipid-raising effect in individuals with the mutation.

Adolescent↗
PubMed1996

Cardiopulmonary resuscitation training for UK undergraduate dental students.

Cardiopulmonary resuscitation (CPR) is a vital skill which must be mastered by all health care professionals. The General Dental Council recommends that it is taught to all UK dental undergraduates. This study was done to elicit how many schools teach aspects of Basic and Advanced Life Support to their students, how often and whether they assess their students. All UK schools teach Basic Life Support (BLS) at least once, but a lower proportion assess their students formally and only three schools teach BLS in each year of the course. Only 64% (9/14) of respondents thought their students received enough training to be able to cope with the initial stages of an emergency on their own. Thus, although the level of BLS training is probably acceptable at present, further improvement of CPR training in UK Dental Schools is advisable.

Cardiopulmonary Resuscitation↗
PubMed1996

A survey of advanced trauma life-support training for trainees in acute surgical specialties.

There have been few published data describing the demand for and amount of Advanced Trauma Life Support (ATLS) training received by trainees in acute surgical specialties. We undertook a survey on aspects of ATLS training, questioning all senior house officers in accident and emergency (A & E) medicine, general surgery and orthopaedic surgery in the west of Scotland in January 1995. More general surgical trainees were ATLS trained than orthopaedic or A & E trainees. Ninety-seven per cent of respondents felt ATLS was essential training for FRCS. There were few problems gaining study leave for the courses, but concern was expressed regarding the long waiting lists. ATLS training is therefore thought to be essential for surgical trainees, and the number of ATLS courses needs to be increased to cope with the demand.

Attitude of Health Personnel↗
PubMed1996

T-cell receptor alpha, beta, gamma, and delta chain gene microsatellites show no association with multiple sclerosis.

Genetic predisposition to multiple sclerosis (MS) is determined, in part, by certain HLA genotypes, but the contribution of T-cell receptor (TCR) germline polymorphisms to MS susceptibility is less clear. Reports of disease associations with restriction fragment length polymorphisms of TCR alpha and beta chain genes have been difficult to confirm, and little data is available on the influence of the TCR gamma delta germline in MS. We investigated the TCR alpha, beta, gamma, and delta chain genes of Northern Irish patients with MS using four microsatellite markers of high heterozygosity. There were similar allele frequencies in patients and controls for all microsatellites studied. We conclude there is no convincing evidence for an association of MS with TCR alpha, beta, gamma, and delta chain gene polymorphisms.

Alleles↗
PubMed1996

Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats.

Abnormal CAG expansions in the IT-15 gene are associated with Huntington disease (HD). In the diagnostic setting it is necessary to define the limits of the CAG size ranges on normal and HD-associated chromosomes. Most large analyses that defined the limits of the normal and pathological size ranges employed PCR assays, which included the CAG repeats and a CCG repeat tract that was thought to be invariant. Many of these experiments found an overlap between the normal and disease size ranges. Subsequent findings that the CCG repeats vary by 8 trinucleotide lengths suggested that the limits of the normal and disease size ranges should be reevaluated with assays that exclude the CCG polymorphism. Since patients with between 30 and 40 repeats are rare, a consortium was assembled to collect such individuals. All 178 samples were reanalyzed in Cambridge by using assays specific for the CAG repeats. We have optimized methods for reliable sizing of CAG repeats and show cases that demonstrate the dangers of using PCR assays that include both the CAG and CCG polymorphisms. Seven HD patients had 36 repeats, which confirms that this allele is associated with disease. Individuals without apparent symptoms or signs of HD were found at 36 repeats (aged 74, 78, 79, and 87 years), 37 repeats (aged 69 years), 38 repeats (aged 69 and 90 years), and 39 repeats (aged 67, 90, and 95 years). The detailed case histories of an exceptional case from this series will be presented: a 95-year-old man with 39 repeats who did not have classical features of HD. The apparently healthy survival into old age of some individuals with 36-39 repeats suggests that the HD mutation may not always be fully penetrant.

Adult↗