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Biomedical subjects

Richard Morris

Publications and source records attributed to Richard Morris.

At least 19 recordsLinked to original sources

Memories for life: a review of the science and technology.

This paper discusses scientific, social and technological aspects of memory. Recent developments in our understanding of memory processes and mechanisms, and their digital implementation, have placed the encoding, storage, management and retrieval of information at the forefront of several fields of research. At the same time, the divisions between the biological, physical and the digital worlds seem to be dissolving. Hence, opportunities for interdisciplinary research into memory are being created, between the life sciences, social sciences and physical sciences. Such research may benefit from immediate application into information management technology as a testbed. The paper describes one initiative, memories for life, as a potential common problem space for the various interested disciplines.

Computer Simulation↗

Trauma case management: improving patient outcomes.

BACKGROUND: The purpose of the study was to measure the effect of trauma case management (TCM) on patient outcomes, using practice-specific outcome variables such as in-hospital complication rates, length of stay, resource use and allied health service intervention rates. METHODS: TCM was provided 7 days a week to all trauma patient admissions. Data from 754 patients were collected over 14 months. These data were compared with 777 matched patients from the previous 14 months. RESULTS: TCM greatly improved time to allied health intervention (p<0.0001). Results demonstrated a decrease in the occurrence of deep vein thrombosis (p<0.038) and a trend towards decreased patient morbidity, unplanned admissions to the intensive care unit and operating suite. A reduced hospital stay LOS, particularly in the paediatric and 45-64 years age group was noted. Six thousand six hundred twenty-one fewer pathology tests were performed and the total number of bed days was 483 days less than predicted from the control group. CONCLUSION: The introduction of TCM improved the efficiency and effectiveness of trauma patient care in our institution. This initiative demonstrates that TCM results in improvements to quality of care, trauma patient morbidity, financial performance and resource use.

Adolescent↗

Differential uptake of molecules from the circulation and CSF reveals regional and cellular specialisation in CNS detection of homeostatic signals.

The uptake of hydroxystilbamidine (OHSt, FluoroGold equivalent) and wheat germ agglutinin (WGA), into the hypothalamus, two hours after injections into either the circulation or the cerebrospinal fluid, were compared in adult rats. Following intravenous injection, OHSt was found in astrocytes of the median eminence and medial part of the arcuate nucleus whereas WGA intensely labelled the blood vessels and ependymal cells throughout the hypothalamus. In complete contrast, intracerebroventricular (icv) injection into the lateral ventricle resulted in OHSt uptake by ependymocytes and astrocytes in the area adjacent to the third ventricle, with virtually no uptake in regions taking up this dye following systematic injections, i.e., the median eminence and medial arcuate. Following icv injection WGA labelling was intense in all parts of the ependymal layer of the third ventricle, including the alpha- and beta-tanycytes. Injections into the cisterna magna gave a different pattern of uptake with OHSt being found only in astrocytes in the ventral part of the hypothalamus lateral to the arcuate nucleus whilst WGA uptake was virtually absent. This highlights the regional and cellular specialisation for uptake of molecules from the circulation and CSF. The median eminence and medial arcuate take up molecules from the circulation, with different cell types taking up different molecules. As the CSF flows through the ventricular system, different cells lining the ventricular and subarachnoid spaces take up molecules differentially. Molecules in the CSF appear to be excluded from the median eminence and medial arcuate region.

Animals↗

Prediction of depression in European general practice attendees: the PREDICT study.

BACKGROUND: Prevention of depression must address multiple risk factors. Estimating overall risk across a range of putative risk factors is fundamental to prevention of depression. However, we lack reliable and valid methods of risk estimation. This protocol paper introduces PREDICT, an international research study to address this risk estimation. METHODS/DESIGN: This is a prospective study in which consecutive general practice attendees in six European countries are recruited and followed up after six and 12 months. Prevalence of depression is assessed at baseline and each follow-up point. Consecutive attendees between April 2003 and September 2004 who were aged 18 to 75 were asked to take part. The possibility of a depressive episode was assessed using the Depression Section of the Composite International Diagnostic Interview. A selection of presumed risk factors was based on our previous work and a systematic review of the literature. It was necessary to evaluate the test-retest reliability of a number of risk factor questions that were developed specifically, or adapted, for the PREDICT study. In a separate reliability study conducted between January and November 2003, consecutive general practice attendees in the six participating European countries completed the risk factor items on two occasions, two weeks apart. The overall response rate at entry to the study was 69%. We exceeded our expected recruitment rate, achieving a total of 10,048 people in all. Reliability coefficients were generally good to excellent. DISCUSSION: Response rate to follow-up in all countries was uniformly high, which suggests that prediction will be based on almost a full cohort. The results of our reliability analysis are encouraging and suggest that data collected during the course of PREDICT will have a satisfactory level of stability. The development of a multi-factor risk score for depression will lay the foundation for future research on risk reduction in primary care. Our data will also provide the necessary evidence base on which to develop and evaluate interventions to reduce the prevalence of depression.

Adolescent↗

Behavioural testing and histological assessments of rabbit spinal cord following intrathecal administration of ondansetron.

1. Intrathecal injection of ondansetron has the potential to reduce opioid-related side-effects. The aim of the present study was to determine whether this route of administration produces neuraxial injury. 2. Adult, non-pregnant female New Zealand white rabbits received a single bolus injection of a low (40 microg) or high (4.0 mg) dose of ondansetron into the intrathecal space between the 4th and 5th lumbar vertebrae. In some cases, ondansetron was coadministered with morphine (5 microg/kg). Control animals received a bolus injection of normal saline. Behavioural assessments were conducted at 1 and 24 h to determine overt changes in arousal and mobility, followed by histological evaluation of the excised spinal cord. 3. Of 45 animals investigated, 10 rabbits exhibited modest behavioural evidence of spinal injury, the incidence of which was equally distributed between the treatment groups. Haematoxylin and eosin, along with HAM56, staining of cross-sections of the cervical, thoracic and upper and lower lumbar areas revealed mild signs of inflammation. This, too, was equally distributed between the treatment groups, suggesting that any observed neuraxial injury was the result of needle trauma and not ondansetron neurotoxicity. 4. Collectively, these negative findings support conducting further experiments to fully assess the clinical usefulness of intrathecal ondansetron administration.

Animals↗

Do perceptions of neighbourhood environment influence health? Baseline findings from a British survey of aging.

OBJECTIVES: To investigate the relation between perceived neighbourhood environment, social contact and support, and self efficacy, on the health of older people. DESIGN: British cross sectional population survey of people aged 65 and over. PARTICIPANTS: 999 people aged 65 plus living at home in Britain. RESULTS: Regression modelling showed that high self efficacy had a strong independent association with better self rated health status and physical functioning. Indicators of perceived neighbourhood environment that showed strong associations with both good health and functioning were: perceptions of good quality facilities in the area (social/leisure, facilities for people aged 65+, rubbish collection, health services, transport, closeness to shops, somewhere nice to walk), and high levels of neighbourliness (knows/trusts people). Perceptions of problems in the area (noise, crime, air quality, rubbish/litter, traffic, graffiti) were also predictive of poorer health. Measures of social contact and support did not show any independent associations with health or functioning. CONCLUSIONS: The unique value of this paper is in the simultaneous analysis of associations between perceived neighbourhood, social contact and support, self efficacy, and health. The consistent strength of older people's perceptions of the quality of facilities in their neighbourhoods shows that responsive reinforcement of local infrastructures might have wider health benefits. Also of interest was the strength of self efficacy as a predictor of self rated health and physical functioning. The results have implications for both neighbourhood level interventions and self management programmes in chronic illness.

Aged↗

Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent dye from the circulation express leptin receptors and neuropeptide Y Y1 receptors.

Following systemic injection, several different dyes and markers are found to accumulate rapidly in cells in the arcuate nucleus and median eminence, and the capillaries in this region appear specialised for exchange of molecules. The present study used hydroxystilbamidine (FluoroGold equivalent) to identify cells that take up molecules from the circulation in these regions; 2-6 h following injection, uptake was seen in the external and intermediate zones of the median eminence and the adjacent ventral part of the arcuate nucleus, but not in other regions of the hypothalamus. The labelled cells were small; double-labelling experiments revealed that they expressed glial fibrillary acid protein (GFAP), but not NeuN, Agouti-related protein (AgRP) or beta-endorphin. They had the morphology of astrocytes and were readily distinguished from tanycytes by staining for vimentin. Many of these labelled astrocytes also expressed leptin receptors and neuropeptide Y Y1 receptors. The surrounding neurons that expressed these receptors did not take up this dye. This demonstrates that astrocytes take up molecules from the circulation in the median eminence and adjacent arcuate nucleus, and may have a significant signalling role in regulation of food intake.

Animals↗

Aerodynamic analysis of male-to-female transgender voice.

The attainment of a feminine-sounding voice is a highly desirable goal among male-to-female transgender (MFT) persons, but this goal may be difficult for many to accomplish. The characteristics associated with a feminine vocal quality include increases in fundamental frequency and in vocal breathiness. In this study, we used inverse-filtering of the airflow signal to indirectly assess vocal fold function in 13 MFT persons. Each participant was asked to sustain the vowel /a/ first in her biological male voice and then again in her female voice. In addition, these vowel productions were compared with vowels produced by age-matched biologic women and men. The results of the study revealed a significant increase in maximum flow declination rate during female voice production. Perceptual ratings of a feminine voice were associated with a fundamental frequency (F0) of 180 Hz or greater, although F0 did not differ significantly between male and female voice production. These results are discussed relative to the mechanisms that obtained a feminine-sounding voice.

Adult↗

Glial-mediated neuroprotection: evidence for the protective role of the NO-cGMP pathway via neuron-glial communication in the peripheral nervous system.

The NO-cGMP pathway has emerged as a neuroprotective signaling system involved in communication between neurons and glia. We have previously shown that axotomy or nerve growth factor (NGF)-deprivation of dorsal root ganglion (DRG) neurons leads to increased production of NO and at the same time an increase in cGMP production in their satellite glia cells. Blockade of NO or its receptor, the cGMP synthesizing enzyme soluble guanylate cyclase (sGC), results in apoptosis of neurons and glia. We now show that co-culture of neonatal DRG neurons with either Schwann cells pre-treated with an NO donor or a membrane-permeant cGMP analogue; or neurons maintained in the medium from Schwann cell cultures treated in the same way, prevents neuronal apoptosis. Both NO donor and cGMP treatment of Schwann cells results in synthesis of NGF and NT3. Furthermore, if the Schwann cells are previously infected with adenoviral vectors expressing a dominant negative sGC mutant transgene, treatment of these Schwann cells with an NO donor now fails to prevent neuronal apoptosis. Schwann cells treated in this way also fail to express neither cGMP nor neurotrophins. These findings suggest NO-sGC-cGMP-mediated NGF and NT3 synthesis by Schwann cells protect neurons.

Animals↗

Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery.

BACKGROUND: Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery. METHODS: One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury. RESULTS: A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005). CONCLUSION: In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.

Acute Kidney Injury↗

Effect of ethnicity and gender on performance in undergraduate medical examinations.

OBJECTIVE: To assess the effect of ethnicity and gender on medical student examination performance. DESIGN: Cohort study of Year 3 medical students in 2002 and 2003. SETTING: Royal Free and University College Medical School, Imperial College School of Medicine. SUBJECTS: A total of 1216 Year 3 medical students, of whom 528 were male and 688 female, and 737 were white European and 479 Asian. OUTCOME MEASURE: Performance in summative written and objective structured clinical examinations (OSCEs) in July 2002 and 2003. RESULTS: White females performed best in all OSCEs and in 3 out of 4 written examinations. Mean scores for each OSCE and 2 out of 4 written examinations were higher for white students than for Asian students. The overall size of the effect is relatively small, being around 1-2%. CONCLUSION: Students of Asian origin, of both genders, educated in the UK, using English as their first language, continue to perform less well in OSCEs and written assessments than their white European peers.

Asian People↗

SMART tubing presents an increased risk of disconnection during extracorporeal circulation.

A number of products exhibiting biocompatible features have been developed for use in extracorporeal blood circuits during cardiopulmonary bypass procedures. While attention has been focused on biocompatibility features of the blood-circuit interface, a number of issues applicable in clinical use of these circuits have arisen. Surface Modifying Additive Technology (SMART; Cobe Cardiovascular, Arvarda, CO) is one such technology. In this product, the structure of normal polyvinylchloride (PVC) tubing is altered through the blending of two copolymers to give a more biocompatible blood to plastic interface. In this study, we examined the in vitro mechanical ability of random samples (n = 10) of SMART and standard PVC tubing to withstand axial tension when the tubing was placed over a single barb of a connector. The tension required to remove the SMART tubing from the connector (83.3 +/- 7.3 [SD] N), was significantly less than standard PVC tubing (115.6 +/- 15.9 N; p < .0001, unpaired t test). The SMART tubing exhibited a 28% reduction in tubing to connector adhesion, which may have a significant effect on extracorporeal circuit disconnection and overall patient safety.

Accident Prevention↗

Either nitric oxide or nerve growth factor is required for dorsal root ganglion neurons to survive during embryonic and neonatal development.

During early embryonic (E12) development almost all dorsal root ganglion (DRG) neurons express the neuronal isoform of nitric oxide synthase (nNOS). At this stage, the axons of these neurons are rudimentary and have not made contact with peripheral tissue targets. As their axons establish contact with peripheral targets such as the skin, the number of neurons expressing nNOS decrease that correspond to increased immunoreactivity for nerve growth factor (NGF) in the skin, and its high affinity receptor, tyrosine kinase A (trkA) in both skin and DRG neurons. During late postnatal development, very few DRG neurons express nNOS; however, axotomy or NGF deprivation of cultured DRG neurons induce nNOS and NOS blockade causes neuronal death. In contrast, NGF-deprived embryonic and neonatal DRG neurons die by apoptosis, while NOS blockade has no effect. Overall, these observations suggest that NGF and nitric oxide (NO) interact during embryonic and postnatal development to facilitate neuronal selection and survival. The roles of NO, NGF and its receptor trkA in DRG neurons during different stages of development are discussed.

Age Factors↗

Methodology for estimating regional and global trends of child malnutrition.

BACKGROUND: Child malnutrition is an important indicator for monitoring progress towards the Millennium Development Goals (MDG). This paper describes the methodology developed by the World Health Organization (WHO) to derive global and regional trends of child stunting and underweight, and reports trends in prevalence and numbers affected for 1990-2005. METHODS: National prevalence data from 139 countries were extracted from the WHO Global Database on Child Growth and Malnutrition. A total of 419 and 388 survey data points were available for underweight and stunting, respectively. To estimate trends we used linear mixed-effect models allowing for random effects at country level and for heterogeneous covariance structures. One model was fitted for each United Nation's region using the logit transform of the prevalence and results back-transformed to the original scale. Best models were selected based on explicit statistical and graphical criteria. RESULTS: During 1990-2000 global stunting and underweight prevalences declined from 34% to 27% and 27% to 22%, respectively. Large declines were achieved in Eastern and South-eastern Asia, while South-central Asia continued to suffer very high levels of malnutrition. Substantial improvements were also made in Latin America and the Caribbean, whereas in Africa numbers of stunted and underweight children increased from 40 to 45, and 25 to 31 million, respectively. CONCLUSION: Linear mixed-effect models made best use of all available information. Trends are uneven across regions, with some showing a need for more concerted and efficient interventions to meet the MDG of reducing levels of child malnutrition by half between 1990 and 2015.

Child↗

Estimates of global prevalence of childhood underweight in 1990 and 2015.

CONTEXT: One key target of the United Nations Millennium Development goals is to reduce the prevalence of underweight among children younger than 5 years by half between 1990 and 2015. OBJECTIVE: To estimate trends in childhood underweight by geographic regions of the world. DESIGN, SETTING, AND PARTICIPANTS: Time series study of prevalence of underweight, defined as weight 2 SDs below the mean weight for age of the National Center for Health Statistics and World Health Organization (WHO) reference population. National prevalence rates derived from the WHO Global Database on Child Growth and Malnutrition, which includes data on approximately 31 million children younger than 5 years who participated in 419 national nutritional surveys in 139 countries from 1965 through 2002. MAIN OUTCOME MEASURES: Linear mixed-effects modeling was used to estimate prevalence rates and numbers of underweight children by region in 1990 and 2015 and to calculate the changes (ie, increase or decrease) to these values between 1990 and 2015. RESULTS: Worldwide, underweight prevalence was projected to decline from 26.5% in 1990 to 17.6% in 2015, a change of -34% (95% confidence interval [CI], -43% to -23%). In developed countries, the prevalence was estimated to decrease from 1.6% to 0.9%, a change of -41% (95% CI, -92% to 343%). In developing regions, the prevalence was forecasted to decline from 30.2% to 19.3%, a change of -36% (95% CI, -45% to -26%). In Africa, the prevalence of underweight was forecasted to increase from 24.0% to 26.8%, a change of 12% (95% CI, 8%-16%). In Asia, the prevalence was estimated to decrease from 35.1% to 18.5%, a change of -47% (95% CI, -58% to -34%). Worldwide, the number of underweight children was projected to decline from 163.8 million in 1990 to 113.4 million in 2015, a change of -31% (95% CI, -40% to -20%). Numbers are projected to decrease in all subregions except the subregions of sub-Saharan, Eastern, Middle, and Western Africa, which are expected to experience substantial increases in the number of underweight children. CONCLUSIONS: An overall improvement in the global situation is anticipated; however, neither the world as a whole, nor the developing regions, are expected to achieve the Millennium Development goals. This is largely due to the deteriorating situation in Africa where all subregions, except Northern Africa, are expected to fail to meet the goal.

Body Weight↗

Spinal dorsal horn neurone targets for nociceptive primary afferents: do single neurone morphological characteristics suggest how nociceptive information is processed at the spinal level.

It has become increasingly clear that nociceptive information is signalled by several anatomically distinct populations of primary afferents that target different populations of neurones in the spinal cord. It is probable that these different systems all give rise to the sensation pain and hence, an understanding of their separate roles and the processes that they employ, may offer ways of selectively targeting pain arising from different causes. The review focuses on what is known of the anatomy of neurones in LI-III of the spinal dorsal horn that are implicated in nociception. The dendritic geometry and synaptic input of the large LI neurones that receive input from primary afferents containing substance P that express neurokinin 1 (NK(1)) receptors suggests that these neurones may monitor the extent of injury rather than the specific localisation of a discrete noxious stimulus. This population of neurones is also critically involved in hyperalgesia. In contrast neurones in LII with the morphology of stalked cells that receive primary afferent input from glomerular synapses may be more suitable for fine discrimination of the exact location of a noxious event such as a sting or parasite attack. The review focuses as far as possible on precisely defined anatomy in the belief that only by understanding these anatomical relationships will we eventually be able to interpret the complex processes occurring in the dorsal horn. The review attempts to be an accessible guide to a sometimes complex and highly specialised literature in this field.

Afferent Pathways↗

Evaluating the impact of population and high-risk strategies for the primary prevention of cardiovascular disease.

AIMS: To estimate the potential effectiveness of different "high-risk" and "population" approaches to the primary prevention of cardiovascular disease (CVD) in middle-aged British men, after correction for regression dilution bias. METHODS AND RESULTS: We used a combination of cohort and randomised controlled trial evidence to estimate the effectiveness of high-risk strategies, based on the identification of high-risk factors or high absolute risk, and strategies based on population-wide reductions in cholesterol and blood pressure. High-risk strategies were potentially effective but would need to be used widely to have a substantial effect on CVD in the population. Aggressive pharmacological treatment (using statins, beta-blockers, ACE-inhibitors and aspirin) in individuals with a 10-year Framingham event risk of >or=30% (6% of population) would have reduced major CVD by at most 11%. This figure increased to 34% at a >or=20% treatment threshold (26% of population). In contrast, modest downwards shifts in the population distributions of serum total cholesterol and systolic blood pressure led to marked expected reductions in major CVD. Taking regression dilution bias into account, 10% reductions in long-term mean blood cholesterol and blood pressure could have reduced major CVD by 45%. CONCLUSIONS: If high-risk strategies are to have a major impact on CVD in the population, they need to be more widely used than previously envisaged. Population-wide reduction of major risk factors is needed if CVD is to be substantially reduced.

Cardiovascular Diseases↗