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D Lyons

Publications and source records attributed to D Lyons.

At least 19 recordsLinked to original sources

Preliminary work on the development of a novel detection method for osteoporosis.

Osteoporosis affects both the organic and mineral phases of bone resulting in a decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are used for diagnosing osteoporosis, which is conventionally characterised by a decrease in mineral density. Unfortunately, some patients who suffer osteoporotic fractures have normal bone density, because both the organic and the mineral phase are affected. However, there are currently no methods of evaluating the health of the organic phase. Patients undergoing treatment for osteoporosis have reported hardening of their fingernails. As the properties of nail and bone may be linked in a comparable, measurable way, this work used both mechanical (nano-indentation) and chemical (Raman spectroscopy) methods to evaluate differences between fingernails sourced from osteoporotic and non-osteoporotic patients. The difference in mean modulus between the nails sourced from the groups was 1.1 GPa. The disulphide bond content of fingernail samples from each group was measured by Raman spectroscopy and disulphide bond content of fingernail was found to be significantly lower in the osteoporotic group. It can be concluded that a relationship between the mechanical and chemical properties of nail and bone may exist in a measurable way. This work has suggested that changes in the organic phase of bone are reflected in similar proteins, such as keratin, from which fingernails are composed. Collagen and keratin are two distinct structural proteins, but they share the need for protein sulphation and disulphide bond formation, via cysteine, for their structural integrity. A disorder of either process should lead to disordered collagen and keratin synthesis.

Bone Density↗

Selective AT1 receptor antagonism enhances sympathetically mediated vasoconstriction in man.

The vasoconstrictive action of angiotensin II (AII) is partly, sympathetically mediated and angiotensin-converting enzyme (ACE) inhibitors appear to exert a sympatholytic effect. We examine the effect of an orally administered, selective AT(1) receptor antagonist (losartan 50 mg) on sympathetically mediated vasoconstriction in healthy volunteers in an observer blind crossover study. Seven healthy, normotensive volunteers (21-32 years), were studied on two occasions at the end of each 6-week treatment period (losartan or placebo). Forearm blood flow (FABF) (ml/dl forearm/min) was measured by venous occlusion plethysmography during the application of lower body negative pressure (LBNP) (-20 cm H(2)O) and at the end of each incremental infusion of norepinephrine (60, 120, and 240 pmol/min). Comparison of blood flow changes was by repeated measures analysis of variance; P<0.05 was taken as statistically significant. Losartan did not alter blood pressure compared to placebo. It did significantly enhance LBNP-induced vasoconstriction in both the left arm compared to placebo (-36.6+/-3.4 vs -23.5+/-3.3%; P=0.017) and the right arm compared to placebo (-39.5+/-3.8 vs -21.0+/-3.6%; P=0.005). The FABF response to all doses of infused norepinephrine (60, 120, and 240 pmol/min) was also enhanced by losartan compared to placebo (-35.0+/-2.7 vs -18.2+/-6.0%; -43.6+/-4.3 vs -28.6+/-5.8%, and -53.9+/-3.2 vs -42.5+/-6.8%; P=0.057, respectively. Losartan enhances locally mediated sympathetic vasoconstriction in the forearm circulation of man, probably through its effect on circulating AII concentrations and we postulate that the adrenergic sympathetic constrictor action of AII is not mediated by the AT(1) receptor or is surmountable at this receptor.

Adult↗

A description of an accelerometer-based mobility monitoring technique.

Accurate monitoring of the mobility status of older adults, over the long-term, is important in rehabilitation medicine, as regular physical activity is central to maintaining both physical and mental health, as well as evaluating quality of life. This technical note describes an accelerometer-based mobility monitoring technique, which can distinguish between static and dynamic activities and can detect the basic postures of sitting, standing and lying. The technique allows thresholds for these postures to be set and two different posture threshold methods are described: mid-point and "best estimate". Preliminary results from using these methods are presented. This preliminary evaluation of the technique was carried out over the long-term (>29 h) in an uncontrolled environment and the method used to carry out the evaluation is described in detail. The two different posture thresholding methods were tested on long-term mobility data from one older adult subject. The subject did not have to follow a specific activity protocol during the recording period (4 days) and was shadowed by an observer in order to evaluate the accuracy of this technique. The monitoring hardware consisted of two accelerometer devices, one on the trunk and the other on the thigh and a pocket-sized ambulatory data-logger. Applying 'best estimate' thresholding, as opposed to mid-point thresholding, improved sitting detection accuracy by 18%, to 93% and lying detection accuracy by 5%, to 84%. Thus, based on these preliminary data, an accurate mobility monitoring system for older adults is described and it was observed that the actual posture threshold limits applied have a high impact on the mobility monitoring system's accuracy and are particularly important for accurately detecting postures when used over the long-term, in an uncontrolled environment.

Acceleration↗

The use of fingernails as a means of assessing bone health: a pilot study.

BACKGROUND: Anecdotally, patients volunteer reports of increasing hardness of their fingernails within months of starting diverse treatments for osteoporosis. The properties of both nail and bone may be linked in a comparable, measurable way. METHODS: We examined the fingernails of two groups of patients, with (n = 9) and without (n = 13) osteoporosis at either the hip or lumbosacral spine. We performed nanoindentation to assess the degree of nail brittleness and Raman spectroscopy to assess the disulfide bond content of nail. RESULTS: The mean moduli of fingernails of patients with low bone mineral density (BMD) are lower than those of patients with normal BMD. The mean difference in mean modulus between the groups was found to be 0.996 (p = 0.15 between groups). The spectroscopy data also showed differences between the two sets of nails. The disulfide bond content of the nails sourced from osteoporotic patients was lower than that from healthy patients (p = 0.06 between groups). CONCLUSIONS: Bone collagen and nail keratin are two distinct structural proteins, and both require protein sulfation and disulfide bond formation, via cysteine, for structural integrity. A disorder of either process may lead to disordered collagen and keratin synthesis. This is reflected in the structural abnormalities seen in clinical syndromes in which there is either protein deficiency, disorders of sulfur metabolism, or cystathione beta-synthase deficiency. The relationship between nail and bone may exist in a measurable way. This pilot study should lead to further work to explore this relationship. Could nail prove to be a valuable adjunct to diagnosis or provide a means of more rapid follow-up after commencement of therapy?

Aged↗

Accelerometers in rehabilitation medicine for older adults.

Recent technological developments have led to the production of inexpensive, miniature accelerometer sensors with potential for use in a clinical setting. These sensors can provide reliable information on mobility and objective measurement of gait. They are currently used mainly in a research setting; however, with recent advances, incorporation into clinical practice is possible. For illustrative purposes this paper describes some current applications of accelerometers in gait and balance evaluation, falls risk assessment and mobility monitoring. Accelerometers provide quantitative measures of gait, they are capable of identifying specific gait changes in older adults and in fallers and can be used to objectively quantify ambulatory activity levels. Accelerometers have many potential uses in monitoring of patients in rehabilitation. They provide an added objective and quantitative dimension to gait analysis when combined with clinical assessment. They have the potential in the future to stratify falls risk facilitating early initiation of appropriate therapeutic intervention, thus reducing further falls. The challenge facing clinicians and biomedical engineers is to further harness this technology making it part of everyday clinical practice.

Acceleration↗

Long-term mobility monitoring of older adults using accelerometers in a clinical environment.

OBJECTIVE: To assess the accuracy of accelerometer-based mobility monitoring during extended measurements on older adults in a clinical setting and to evaluate two different approaches to thresholding. DESIGN: The monitoring device consisted of two Analog Devices ADXL202 accelerometers, an ambulatory data-logger and associated cabling. The monitoring system used custom-designed analysis software to detect activities of daily living, namely duration of sitting, standing, lying and moving during the period monitored. An investigator shadowed the subjects throughout the recording period. SUBJECTS AND SETTING: This study monitored five older adults, with varying degrees of mobility, resident in a rehabilitation clinic, over four days. INTERVENTIONS: The accelerometer data were analysed using a MATLAB program that allowed trunk and thigh threshold angles to be set to distinguish between sitting, standing, lying and moving. Two different approaches to setting these thresholds were investigated: (1) using a midpoint tolerance value of 45 degrees and (2) using a 'best estimate' tolerance value. The analysis program generates a summary of activities, which is then compared line-by-line with the manual summary created by the observer. The result was a hit/miss ratio representative of the system's accuracy. RESULTS: The detection accuracies for sitting and lying using a mid-point tolerance value were poor, with an average detection accuracy of 75% obtained. The 'best estimate' approach improved the detection accuracies for sitting and lying by approximately 18% to an average value of 93%. CONCLUSION: In a population of older adults, the static activities of sitting, standing and lying and dynamic activities can be distinguished using the technique and threshold values outlined here to a degree of accuracy of 92% and higher.

Activities of Daily Living↗

The cardiovascular system.

The ageing process is associated with important changes in the responses of the cardiovascular system to pharmacological stimuli. They are not limited to the arterial system, involved in the modulation of cardiac afterload and vascular resistance, but they also involve the low-resistance capacitance venous system and the heart. The main changes include loss of large artery compliance, dysfunction of some of the systems modulating resistance vessel tone, increased activity of the sympathetic nervous system, and reduced haemodynamic responses to inotropic agents. This review focuses on the effects of ageing on arterial and venous reactivity to drugs and hormones, the autonomic nervous system, and the cardiovascular responses to inotropic agents. Some of the age-related changes might be at least partially reversible. This may have important therapeutic implications.

Aging↗

Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis.

Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints. The goal of this phase-I/II study in adults with rheumatoid arthritis (RA) was to evaluate the safety and clinical activity of different doses and schedules of rhIL-11 in patients with active RA for whom treatment with at least one disease-modifying antirheumatic drug had failed. This was a multicenter, randomized, placebo-controlled trial that evaluated the safety and tolerability of rhIL-11 in 91 patients with active RA. rhIL-11 was administered subcutaneously; patients were randomized into one of five treatment groups (ratio of rhIL-11 to placebo, 4:1). Patients were treated for 12 weeks with either 2.5 or 7.5 microg/kg of rhIL-11 or placebo twice per week or 5 or 15 microg/kg of rhIL-11 or placebo once per week. The status of each subject's disease activity in accordance with the American College of Rheumatology (ACR) criteria was assessed before, during, and after completion of administration of the study drug. Administration of rhIL-11 was well tolerated at all doses and schedules. The most frequent adverse event was a reaction at the injection site. The data suggest a statistically significant reduction in the number of tender joints (P < 0.008) at the 15 microg/kg once-weekly dose schedule but showed no overall significant benefit at the ACR criterion of a 20% response. The trial showed rhIL-11 to be safe and well tolerated at a variety of doses and schedules over a 12-week treatment period in patients with active RA. The only adverse event clearly associated with rhIL-11 administration was reaction at the injection site.

Adult↗

Behavioural management of aggression in dementia: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of a brief behaviour management training programme for family carers of patients with dementia and aggressive behaviour. DESIGN: A randomized controlled trial of a four-session, community-based behaviour management programme. The primary outcome measure was the Rating Scale for Aggressive Behaviour in the Elderly. PARTICIPANTS: 62 patients with dementia, and their co-resident carers. RESULTS: There were no significant differences in aggression scores between behaviour management and control groups at follow-up. After adjusting for baseline differences in Rating Scale for Aggressive Behaviour in the Elderly scores, there was a trend towards a reduction in aggressive behaviour in the patients in the behaviour management group compared with those in the control group (F = 3.37, P = 0.071). CONCLUSIONS: This study adds to the small evidence base for the effectiveness of behavioural management strategies in dementia.

Aged↗

Absence of abdominal pain in older persons with endoscopic ulcers: a prospective study.

OBJECTIVE: In a retrospective study we reported absence of abdominal pain in 35% of elderly patients with peptic ulcer disease. We now report a prospective study on this question. METHODS: Patients undergoing upper GI endoscopy were systematically questioned before endoscopy. A reproducible method for identifying the location of symptoms was used. Among patients referred for upper endoscopy, there was no selection of patients for study purposes as all had strong indications, such as pain, dyspepsia, GI bleeding, weight loss, or anemia. Patients were divided into two groups according to age: A younger group consisting of patients <50 yr (mean, 33.6 yr) and an older group >60 yr (mean, 70.9 yr). RESULTS: A total of 277 patients were included in the study. There was no significant difference in reported use of medications, alcohol, or cigarette use between the groups. Of the 106 patients with peptic ulcer, 15 (14.2%) had not experienced pain. Abdominal pain was absent in 5 (6.9%) of the younger patients and 10 (29.4%) of the older patients. The difference was significant using the chi2 method (p = 0.004). A trend toward an even higher proportion of pain-free peptic ulcer disease was noted in the elderly female group (37.5%), but it did not reach statistical significance. CONCLUSIONS: Absence of abdominal pain is confirmed in approximately 30% of elderly patients with peptic ulcer disease.

Abdominal Pain↗

Insulin-like growth factor-1 selectively increases glucose utilization in brains of aged animals.

Previous studies indicate that insulin-like growth factor-1 is an important neurotrophic agent and that decreases in brain concentrations of IGF-1 and the type 1 IGF receptor have an important role in the age-related decline in memory, neuronal function and possibly dendritic architecture. In this study, we assessed the effects of age and IGF-1 replacement on local cerebral glucose utilization (LCGU). Three groups of male Brown-Norway rats (7, 18 and 28 months of age) were implanted with Alzet minipumps and either saline or IGF-1 (50ng/0.5 microliter/hour) was infused into the lateral ventricle for 28 days. On day 28, LCGU was measured by infusion of 2-[(14)C]deoxyglucose during the dark phase of the light/dark cycle. Results indicate that glucose utilization significantly decreased with age throughout the brain including the anterior cingulate, sensorimotor and retrosplenial cortex, CA1, CA3 and dentate gyrus of hippocampus and several regions of the hypothalamus. Administration of IGF-1 to aged animals increased rates of LCGU in the anterior cingulate of the cortex (14.2%), CA1 region of the hippocampus (11.0%) and the arcuate nucleus of the hypothalamus (12.0%). Our results indicate that although glucose utilization decreases with age throughout the brain, the effects of IGF-1 infusion are manifest only in specific brain regions. Since IGF-1 has been shown to reverse the age-related decrease in memory, these results suggest that despite the wide distribution of the type 1 IGF receptor the actions of IGF-1 on glucose utilization are highly localized. Additionally, the close association between glucose utilization and excitatory amino acid activity suggests that IGF-1 may act on specific neural pathways to increase glutamate activity in brain regions associated with learning and memory.

Aging↗

Adults with Incapacity (Scotland) Act 2000: implications for medical practice.

The Scottish Parliament has passed a major piece of Legislation, The Adults with Incapacity (Scotland) Act 2000. Various Sections of this Act will be implemented on a phased basis between April 2001 and April 2002. This article summarises the major provisions of the Act and describes the duties of doctors and the impact on medical treatment and research where the person is incapable of giving consent.

Financial Management↗

Sphingosylphosphorylcholine induces endothelial cell migration and morphogenesis.

Sphingosylphosphorylcholine (SPC) is one of the biologically active phospholipids that may act as extracellular messengers. Particularly important is the role of these lipids in the angiogenic response, a complex process involving endothelial cell migration, proliferation, and morphologic differentiation. Here we demonstrate that SPC and its hydrolytic product, sphingosine, induce chemotactic migration of human and bovine endothelial cells. The response is approximately equal to that elicited by vascular endothelial cell growth factor. The effect of SPC and sphingosine was associated with a rapid down-regulation of Edg1, a sphingosine 1-phosphate (SPP)-specific receptor involved in endothelial cell chemotaxis. Both SPC and sphingosine induced differentiation of endothelial cells into capillary-like structures in vitro. Thus, SPC and sphingosine join SPP among the biologically active lipids with angiogenic potential. Since neuronal abnormalities accompany pathological accumulation of SPC in brain tissue, it is possible that SPC is a modulator of angiogenesis in neural tissue upon its release from brain cells following trauma or neoplastic growth.

Animals↗

The nature and frequency of blood contacts among home healthcare workers.

OBJECTIVE: To estimate the frequency of, and assess risk factors for, percutaneous, mucous membrane, and cutaneous blood contacts sustained by healthcare workers (HCWs) during the delivery of infusion therapy and the performance of procedures involving sharp instruments in the home setting. DESIGN: Prospective surveillance of percutaneous, mucous membrane, and cutaneous blood contacts. SETTING: Eleven home healthcare agencies in the United States and Canada from August 1996 through June 1997. PARTICIPANTS: HCWs who provided home infusion therapy or performed procedures using hollow-bore needles and other sharp instruments in the home setting. METHODS: Each participating worker recorded information about the procedures performed and blood contacts experienced during each of his or her home visits for a 2- to 4-week period using standard questionnaires. HCWs also completed questionnaires regarding job duties, reporting of previous occupational blood contacts, and their use of protective barriers in the home setting. RESULTS: Participating HCWs provided information about 33,606 home visits. A total of 19,164 procedures were performed during 14,744 procedure visits. Fifty-three blood contacts occurred during these visits, for a blood-contact rate of 2.8 blood contacts per 1,000 procedures and 0.6 percutaneous injuries per 1,000 procedures with needles or lancets. Gloves were worn for 52%, masks for 5%, gowns for 3%, and protective glasses or goggles for 2% of all procedure visits. HCWs used barriers for 53% of visits during which at least 1 procedure was performed and for 27% of other visits. CONCLUSIONS: HCWs involved in home health care are at risk for blood contact. Infection control barrier use was low in our study. The majority of skin contacts could have been prevented by glove use.

Blood-Borne Pathogens↗

Orbital and medial prefrontal cortex and psychostimulant abuse: studies in animal models.

One approach to pursuing questions about the neural substrates that support substance abuse-related behaviors involves the use of animal models. Carefully controlled animal experiments can be conducted without the confounds commonly found in studies of human addicts, such as polydrug abuse, variable drug history and premorbid psychiatric conditions. The present paper considers the orbitofrontal and related limbic prefrontal cortex in the context of such models of substance abuse. First, the importance of recognizing the heterogeneous structural and functional nature of orbitofrontal cortex in both rodents and primates is addressed, and the results of studies involving the prefrontal cortex in substance abuse-related behaviors are considered in light of this diversity. Second, data from metabolic mapping studies are described that indicate that the pattern of functional activity within medial and orbitofrontal cortex shifts as the duration of exposure to drugs such as cocaine is extended. These functional differences, in turn, may reflect progressive phases of the addictive process. In order to understand the neurobiological consequences of long-term drug use, it will be important to establish the differing roles played by distinct anatomical territories within orbital and medial prefrontal cortex during the course of chronic substance abuse.

Animals↗