PubMed Health⌕ Search

Biomedical subjects

Andrew Morris

Publications and source records attributed to Andrew Morris.

At least 19 recordsLinked to original sources
PubMed2006

An approach to the derivation of the cost of UK vehicle crash injuries.

An approach to costing of road crash injury has been developed using data from a 'Willingness-to-pay' survey mapped to injuries listed in the Abbreviated Injury Scale 1998 Revision. The costs derived have been applied to a database of real-world crash injuries that have been collected as part of the UK Cooperative Crash Injury Study (CCIS). The approach has been developed in order to determine future research priorities in vehicle passive safety. When all injuries in all crash-types are examined, the results highlight the cost of 'Whiplash' in the UK. When more serious injuries are considered, specifically those at AIS 2+, the cost of head injuries becomes evident in both frontal and side impacts.

Abbreviated Injury Scale↗
PubMed2005

Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT.

Autism is a highly heritable neurodevelopmental disorder whose underlying genetic causes have yet to be identified. To date, there have been eight genome screens for autism, two of which identified a putative susceptibility locus on chromosome 16p. In the present study, 10 positional candidate genes that map to 16p11-13 were examined for coding variants: A2BP1, ABAT, BFAR, CREBBP, EMP2, GRIN2A, MRTF-B, SSTR5, TBX6, and UBN1. Screening of all coding and regulatory regions by denaturing high-performance liquid chromatography identified seven nonsynonymous changes. Five of these mutations were found to cosegregate with autism, but the mutations are not predicted to have deleterious effects on protein structure and are unlikely to represent significant etiological variants. Selected variants from candidate genes were genotyped in the entire International Molecular Genetics Study of Autism Consortium collection of 239 multiplex families and were tested for association with autism by use of the pedigree disequilibrium test. Additionally, genotype frequencies were compared between 239 unrelated affected individuals and 192 controls. Patterns of linkage disequilibrium were investigated, and the transmission of haplotypes across candidate genes was tested for association. Evidence of single-marker association was found for variants in ABAT, CREBBP, and GRIN2A. Within these genes, 12 single-nucleotide polymorphisms (SNPs) were subsequently genotyped in 91 autism trios (one affected individual and two unaffected parents), and the association was replicated within GRIN2A (Fisher's exact test, P<.0001). Logistic regression analysis of SNP data across GRIN2A and ABAT showed a trend toward haplotypic differences between cases and controls.

4-Aminobutyrate Transaminase↗
PubMed2005

Lipid phosphate phosphatase-1 regulates lysophosphatidic acid-induced calcium release, NF-kappaB activation and interleukin-8 secretion in human bronchial epithelial cells.

LPA (lysophosphatidic acid), a potent bioactive phospholipid, elicits diverse cellular responses through activation of the G-protein-coupled receptors LPA1-LPA4. LPA-mediated signalling is partially regulated by LPPs (lipid phosphate phosphatases; LPP-1, -2 and -3) that belong to the phosphatase superfamily. This study addresses the role of LPPs in regulating LPA-mediated cell signalling and IL-8 (interleukin-8) secretion in HBEpCs (human bronchial epithelial cells). Reverse transcription-PCR and Western blotting revealed the presence and expression of LPP-1-3 in HBEpCs. Exogenous [3H]oleoyl LPA was hydrolysed to [3H]-mono-oleoylglycerol. Infection of HBEpCs with an adenoviral construct of human LPP-1 for 48 h enhanced the dephosphorylation of exogenous LPA by 2-3-fold compared with vector controls. Furthermore, overexpression of LPP-1 partially attenuated LPA-induced increases in the intracellular Ca2+ concentration, phosphorylation of IkappaB (inhibitory kappaB) and translocation of NF-kappaB (nuclear factor-kappaB) to the nucleus, and almost completely prevented IL-8 secretion. Infection of cells with an adenoviral construct of the mouse LPP-1 (R217K) mutant partially attenuated LPA-induced IL-8 secretion without altering LPA-induced changes in intracellular Ca2+ concentration, phosphorylation of IkappaB, NF-kappaB activation or IL-8 gene expression. Our results identify LPP-1 as a key regulator of LPA signalling and IL-8 secretion in HBEpCs. Thus LPPs could represent potential targets in regulating leucocyte infiltration and airway inflammation.

Adenoviridae↗
PubMed2005

Designing the European Road Safety Observatory.

The unavailability of consistent traffic accident data and road safety information limits the opportunities to provide target approaches to reduce road crashes. The European commission has decided to meet the demand for this data by establishing a new Road Safety Observatory. The structure and much of the initial content is being developed within the SafetyNet Integrated Project. This paper describes the structure of its key components.

Accidents, Traffic↗
PubMed2005

Predicting vascular risk in Type 1 diabetes: stratification in a hospital based population in Scotland.

AIMS: To estimate the absolute cardiovascular risk of patients with Type 1 diabetes attending hospital diabetes clinics in Scotland and to develop a method for identifying those at highest risk, thus enabling therapy to be targeted. METHODS: Baseline information was collected for 2136 patients with Type 1 diabetes using the Royal College of Physicians of Edinburgh Diabetes Register. These records were then linked to diagnoses of macrovascular disease in databases of the Information Statistics Division of the Common Services Agency. RESULTS: During six to nine years of follow up 110 patients (5%) developed macrovascular disease. There were significant associations between baseline age (P < 0.00001), blood pressure (P < 0.00001), albuminuria (P < 0.0002), HbA1c (P < 0.001), cholesterol (P < 0.00001) and smoking status (P < 0.00001) with the development of macrovascular disease. A scoring system for future macrovascular risk was developed from a multivariate analysis of this data. CONCLUSIONS: The data confirm the high vascular risk of patients with Type 1 diabetes. The relationship with age is such that those patients above 50 years require only one additional risk factor to reach such a high vascular risk that intervention is indicated. Using these data many patients between the age of 40 and 49 years are also likely to be identified to be at high risk.

Adult↗
PubMed2005

Do losartan and atenolol have differential effects on BNP and central haemodynamic parameters?

INTRODUCTION: It has been suggested that angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) have a differential effect on brachial and aortic haemodynamics. This is why they seem to have beneficial effects that are beyond brachial blood pressure (BP) lowering. We aimed to investigate if this was the case with losartan when compared to atenolol. We also investigated the differential effect of losartan and atenolol on the prognostic marker, brain type natriuretic peptide (BNP). METHODS: We studied 17 patients who were similar to those in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Patients were randomised to receive four months of losartan and atenolol in a crossover fashion. Main outcome measures were BNP and Augmentation index (AIx), which gives an indication of central haemodynamics. Brachial pulse wave velocity (PWV) and time to reflected wave (Tr) were measured as an indication of vascular stiffness. RESULTS: BNP was significantly lower on losartan than atenolol (p=0.007). AIx was lower on losartan than atenolol (p=0.03), however, this result was not significant when heart rate was considered as a covariate (p=0.09). Heart rate was significantly lower on atenolol than losartan (p=0.03). There was no difference between treatments for both brachial PWV and Tr (p=0.2 and p=0.99, respectively). CONCLUSION: The benefits seen when losartan was compared to atenolol in the LIFE trial may be due to a reduction in BNP. We failed to detect a differential effect in central compared to peripheral haemodynamics when losartan was compared to atenolol.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Attenuation of vasopressin-induced antidiuresis in poorly controlled type 2 diabetes.

Renal resistance to vasopressin has been demonstrated in type 1 diabetes and in type 2 diabetes with nephropathy. However, renal response to vasopressin in type 2 diabetes without nephropathy has not been studied. We studied 10 subjects with poorly controlled type 2 diabetes (PCDS; Hb A(1c) >9%), 10 subjects with well-controlled type 2 diabetes (WCDS; Hb A(1c) <7%), and 10 matched nondiabetic control subjects (NDCS) during a euglycemic 8-h water deprivation test. None of the subjects had nephropathy. Water deprivation caused similar rises in plasma vasopressin concentrations in all three groups, but the rise in urine osmolality in PCDS (280.3 +/- 49.7 to 594.4 +/- 88.5 mosmol/kgH(2)O) was lower than in WCDS (360.7 +/- 142.8 to 794.1 +/- 77.3 mosmol/kgH(2)O, P < 0.001) or NDCS (336.0 +/- 123.3 to 786.5 +/- 63.3 mosmol/kgH(2)O, P = 0.019). Total urine output was higher in the PCDS than in WCDS and NDCS (P < 0.05). Linear regression analysis showed that, in PCDS, the osmotic thresholds for thirst (291.9 +/- 4.6 mosmol/kgH(2)O) and vasopressin release (291.1 +/- 2.9 mosmol/kgH(2)O) were higher compared with WCDS (286.6 +/- 1.8 and 286.0 +/- 3.6 mosmol/kgH(2)O, respectively) and NDCS (286.0 +/- 2.4 and 284.1 +/- 4.7 mosmol/kgH(2)O, respectively) (between groups P < 0.001 for both variables). Under conditions of euglycemia, PCDS have impaired renal response to vasopressin and elevated osmotic threshold for thirst and vasopressin release in response to dehydration. Under conditions of chronic hyperglycemia, these abnormalities may significantly contribute to the development of dehydration in PCDS.

Aged↗
PubMed2004

Cohort study of forceps delivery and the risk of epilepsy in adulthood.

OBJECTIVE: The purpose of this study was to investigate the relationship between forceps delivery and epilepsy in adulthood. Study design We conducted a cohort study of 21,441 births with record linkage to data from the Tayside Medicine Monitoring unit (MEMO) and Scottish morbidity records (SMR1). RESULTS: Delivery by forceps was not associated with epilepsy compared with all other deliveries, adjusted odds ratio (OR) 1.0 (95 % CI, 0.6-1.8). Epilepsy in adulthood was associated with a family history of epilepsy, adjusted OR 2.4 (95% CI, 1.7-3.2), increasing social deprivation, adjusted OR 1.1 for each Carstairs score (95% CI, 1.0-1.2), and male gender, adjusted OR 1.4 (95% CI, 1.0-1.8). Preterm birth was associated with an increased risk of epilepsy, adjusted OR 2.0 (95% CI, 1.2-3.2) but no other antenatal, intrapartum, or neonatal risk factors were identified. CONCLUSION: These findings do not suggest an association between forceps delivery and epilepsy in adulthood; however, preterm birth may be an important risk factor.

Adult↗
PubMed2004

A comparison of digital retinal image quality among photographers with different levels of training using a non-mydriatic fundus camera.

PURPOSE: To evaluate the quality of digital retinal images taken by three photographers with different levels of photographic training, using a non-mydriatic fundus camera. METHODS: This study compares 45-degree digital retinal images taken with a non-mydriatic fundus camera by three different photographers with different levels of photographic training: (I) A professional ophthalmic photographer with 20 years of experience; (2) a non-professional photographer with 2 days of photographic training and experience with 50 patients; (3) a non-professional photographer with 1 hour of photographic training and experience with 10 patients. The quality of the photographs was evaluated by the consensus of two retina specialists. RESULTS: Sixty-four (64) eyes of 33 subjects were imaged by the three photographers for a total of 192 images. Thirty-four eyes were photographed in the non-dilated state. The trained ophthalmic photographer and the two non-professional photographers did not have statistically significant differences in image quality based on the image evaluations. (Chi-square P-value: 0.57). This finding was consistent for eyes in both the non-dilated and dilated state. CONCLUSIONS: Fundus image quality for images taken with a non-mydriatic camera were not significantly different among three photographers with different levels of training.

Diabetic Retinopathy↗
PubMed2004

Thoracic aortic injury in motor vehicle crashes: the effect of impact direction, side of body struck, and seat belt use.

BACKGROUND: Using in-depth, real-world motor vehicle crash data from the United States and the United Kingdom, we aimed to assess the incidence and risk factors associated with thoracic aorta injuries. METHODS: De-identified National Automotive Sampling System Crashworthiness Data System (U.S.) and Co-operative Crash Injury Study (U.K.) data formed the basis of this retrospective analysis. Logistic regression was used to assess the level of risk of thoracic aorta injury associated with impact direction, seat belt use and, given the asymmetry of the thoracic cavity, whether being struck toward the left side of the body was associated with increased risk in side-impact crashes. RESULTS: A total of 13,436 U.S. and 3,756 U.K. drivers and front seat passengers were analyzed. The incidence of thoracic aorta injury in the U.S. and U.K. samples was 1.5% (n = 197) and 1.9% (n = 70), respectively. The risk was higher for occupants seated on the side closest to the impact than for occupants involved in frontal impact crashes. This was the case irrespective of whether the force was applied toward the left (belted: relative risk [RR], 4.6; 95% confidence interval [CI], 2.9-7.1; p < 0.001) or the right side (belted: RR, 2.6; 95% CI, 1.4-5.1; p < 0.004) of the occupant's body. For occupants involved in side-impact crashes, there was no difference in the risk of thoracic aorta injury whether the impacting force was applied toward the left or toward the right side of the occupant's body. Seat belt use provided a protective benefit such that the risk of thoracic aorta injury among unbelted occupants was three times higher than among belted occupants (RR, 3.0; 95% CI, 2.2-4.3; p < 0.001); however, the benefit varied across impact direction. Thoracic aorta injuries were found to be associated with high impact severity, and being struck by a sports utility vehicle relative to a passenger vehicle (RR, 1.7; 95% CI, 1.2-2.3; p = 0.001). CONCLUSION: Aortic injuries have been conventionally associated with frontal impacts. However, emergency clinicians should be aware that occupants of side-impact crashes are at greater risk, particularly if the occupant was unbelted and involved in a crash of high impact severity.

Accidents, Traffic↗
PubMed2004

Rapidly progressive dementia due to Mycobacterium neoaurum meningoencephalitis.

Dementia developed in a patient with widespread neurologic manifestations; she died within 5 months. Pathologic findings showed granulomatous inflammation with caseation necrosis, foreign body-type giant cells, and proliferative endarteritis with vascular occlusions. Broad-range polymerase chain reaction identified Mycobacterium neoaurum as the possible pathogen. Central nervous system infection by M. neoaurum may result in rapidly progressive dementia.

Dementia↗
PubMed2003

Involvement of phospholipase D2 in lysophosphatidate-induced transactivation of platelet-derived growth factor receptor-beta in human bronchial epithelial cells.

Lysophosphatidate (LPA) mediates multiple cellular responses via heterotrimeric G protein coupled LPA-1, LPA-2, and LPA-3 receptors. Many G protein-coupled receptors stimulate ERK following tyrosine phosphorylation of growth factor receptors; however, the mechanism(s) of transactivation of receptor tyrosine kinases are not well defined. Here, we provide evidence for the involvement of phospholipase D (PLD) in LPA-mediated transactivation of platelet-derived growth factor receptor-beta (PDGF-R beta). In primary cultures of human bronchial epithelial cells (HBEpCs), LPA stimulated tyrosine phosphorylation of PDGF-R beta and threonine/tyrosine phosphorylation of ERK1/2. The LPA-mediated activation of ERK and tyrosine phosphorylation of PDGF-R beta was attenuated by tyrphostin AG 1296, an inhibitor of PDGF-R kinase, suggesting transactivation of PDGF-R by LPA. Furthermore, LPA-, but not PDGF beta-chain homodimer-induced tyrosine phosphorylation of PDGF-R beta was partially blocked by pertussis toxin, indicating coupling of LPA-R(s) to Gi. Exposure of HBEpCs to LPA activated PLD. Butan-1-ol, which acts as an acceptor of phosphatidate generated by the PLD pathway, blocked LPA-mediated transactivation of PDGF-R beta. This effect was not seen with butan-3-ol, suggesting PLD involvement. The role of PLD1 and PLD2 in the PDGF-R beta transactivation by LPA was investigated by infection of cells with adenoviral constructs of wild type and catalytically inactive mutants of PLD. LPA activated both PLD1 and PLD2 in HBEpCs; however, infection of cells with cDNA for wild type PLD2, but not PLD1, increased the tyrosine phosphorylation of PDGF-R beta in response to LPA. Also, the LPA-mediated tyrosine phosphorylation of PDGF-R beta was attenuated by the catalytically inactive mutant mPLD2-K758R. Infection of HBEpCs with adenoviral constructs of wild type hPLD1, mPLD2, and the inactive mutants of hPLD1 and mPLD2 resulted in association of PLD2 wild type and inactive mutant proteins with the PDGF-R beta compared with PLD1. These results show for the first time that transactivation of PDGF-R beta by LPA in HBEpCs is regulated by PLD2.

Base Sequence↗
PubMed2003

Linkage disequilibrium assessment via log-linear modeling of SNP haplotype frequencies.

Analyses of high-density single-nucleotide polymorphism (SNP) data, such as genetic mapping and linkage disequilibrium (LD) studies, require phase-known haplotypes to allow for the correlation between tightly linked loci. However, current SNP genotyping technology cannot determine phase, which must be inferred statistically. In this paper, we present a new Bayesian Markov chain Monte Carlo (MCMC) algorithm for population haplotype frequency estimation, particularly in the context of LD assessment. The novel feature of the method is the incorporation of a log-linear prior model for population haplotype frequencies. We present simulations to suggest that 1) the log-linear prior model is more appropriate than the standard coalescent process in the presence of recombination (>0.02 cM between adjacent loci), and 2) there is substantial inflation in measures of LD obtained by a "two-stage" approach to the analysis by treating the "best" haplotype configuration as correct, without regard to uncertainty in the recombination process.

Algorithms↗
PubMed2003

DARTS 2000 online diabetes management system: formative evaluation in clinical practice.

RATIONALE, AIMS AND OBJECTIVES: Failure to engage in user-informed evaluation of emergent health informatics tools can have negative consequences for future implementation, related both to poor usability or clinical utility and to suboptimal stakeholder buy-in. This paper describes a formative evaluation in primary care of a multifaceted, web-based resource for diabetes management. The primary aims were to assess the usability and utility of the prototype in order to inform system refinements prior to implementation, and to investigate barriers and facilitators to system use so as to aid the development of a tailored implementation plan. METHODS: A mixed-method approach involving survey, remote observation, semi-structured interviews and electronic feedback. CONTEXT: One Scottish local health care cooperative comprising five general practice surgeries and their staff. RESULTS: A survey following temporary exposure to a dummy site revealed high levels of computer familiarity, welcoming attitudes and positive ratings of usability, format and utility. Comments mainly addressed content accuracy, feature suggestions and usability issues. Key barriers and facilitators to use included time and training. Remote observation following access to live clinical data enabled profiling of usage by individual and professional group. In the 3 month observation period administrators were the most frequent users, followed by GPs and nurses, with clinical and data entry screens accessed most often. Semi-structured interviews with key respondents sampled by professional group and usage frequency provided richer qualitative information on barriers and facilitators to use, patterns of system integration into work routines and system usability, content and utility. Content analysis of electronic feedback revealed mainly technical queries and general expressions of satisfaction. CONCLUSIONS: Evaluation informed a number of important and unforeseen improvements to the prototype and helped refine the implementation plan. Engagement in the process of evaluation has led to high levels of stakeholder ownership and widespread implementation.

Attitude to Computers↗
PubMed2003

A preliminary analysis of aortic injuries in lateral impacts.

Injuries to the aorta are among the more serious injuries that result from vehicle impacts, and often may be fatal. This article examines the incidence of aortic injuries in the United States and United Kingdom by using two international databases of real-world crashes. The main outcome of interest was the level of risk associated with each principal direction of force for drivers and front-seat passengers with respect to sustaining aortic injuries. The results indicate that the risk of sustaining an injury to the aorta is greater for near-side crashes than for far-side crashes. Further it is apparent that, given a near-side crash, the risk of an aortic injury is greater on the left side of the body (and left side of the vehicle) than on the right. It also was found that the delta-V of crashes where occupants sustained an injury to the aorta was considerably higher than crashes where occupants did not sustain aortic injuries. It is speculated that the anatomical asymmetry of the thorax might play a role in the differences seen in injury risk associated with different impact directions. The results presented in this article could be of use to both the emergency physician treating patients involved in motor vehicle collisions as well as the engineer involved in occupant design countermeasures. Limitations and further planned research are discussed.

Abbreviated Injury Scale↗