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Biomedical subjects

M Murray

Publications and source records attributed to M Murray.

At least 37 records · Page 2Linked to original sources

Formation of a dihydropyridine derivative as a potential cross-link derived from malondialdehyde in physiological systems.

Malondialdehyde is a major oxidation product of lipids which is capable of cross-linking the collagen of the cardiovascular system. Identification of cross-links usually involves degradative procedures. In this paper, we use a novel, direct, approach using nuclear magnetic resonance to identify early and labile products. Initial model studies show that malondialdehyde reacts with lysine to form a dihydropyridine derivative rather than the unstable imidopropene Schiff base previously reported. The aldehydes on the pyridine ring could react further to cross-link collagen and stiffen the aorta, thereby promoting further glycation, a process that would be accelerated in diabetes.

Cross-Linking Reagents

Critical interval for rescue of axotomized neurons by transplants.

To determine whether embryonic spinal cord transplants retained the ability to prevent retrograde death of Clarke's nucleus (CN) neurons if supplied after a delay, we hemisected adult rats at the T8 spinal cord segment and placed transplants of fetal tissue into the hemisection cavity immediately or up to 14 days later. Transplants provided in the first 7 days after injury prevented virtually all of the 30% loss of CN neurons at L1 ipsilateral to hemisection that occurs without a transplant. Transplants supplied at 14 days post-hemisection were ineffective. Because prevention of retrograde neuron death is one mechanism by which transplants may contribute to locomotor recovery after spinal cord injury, this window of effectiveness should be considered in the design of clinical trials.

Animals

Neurotrophin-3 prevents death of axotomized Clarke's nucleus neurons in adult rat.

In the present investigation, we studied whether neurotrophin-3 (NT-3) contributes to the rescue of axotomized Clarke's nucleus (CN) neurons in adult rats. A significant (24%) loss of CN neurons occurred at L-1 ipsilateral to T-8 hemisection by 14 days, which reached 31% at 2 months and then stabilized. Axotomized CN neurons had also atrophied by 14 days, but mean cell size did not decrease further. Animals that received gelfoam soaked in nerve growth factor, brain derived neurotrophic factor, or ciliary neurotrophic factor at the lesion site also showed a 30% neuron loss at 2 months, and a 40% reduction in average cell area. Rats receiving NT-3 showed a 15% neuron loss, which was not improved by additional neurotrophins in combination with NT-3. None of the treatments prevented neuron atrophy. Bioassay of the gelfoam showed that NT-3 bioactivity remained at 5 days after surgery but not at 14 days. Additional rats with hemisections that received NT-3 continuously via mini-pump for 2 months showed a 15% neuron loss, the same as with NT-3 given via gelfoam. These results indicate that even limited exposure of axotomized CN neurons to NT-3 produces permanent rescue of 50% of the neurons. The virtually complete rescue that we had previously observed with transplants of fetal central nervous system (CNS) tissues may, therefore, be due at least in part to NT-3, but the exogenous administration of a single neurotrophic factor or a combination of neurotrophic factors is less effective than transplants in producing long-term survival of axotomized CNS neurons.

Animals

Induction of presynaptic reexpression of an adhesion protein in lamina II after dorsal root deafferentation in adult rat spinal cord.

Limbic system-associated membrane protein (LAMP), a 64-kDa membrane protein, is an axon guidance adhesion molecule expressed by neurons in limbic system-related areas of the CNS. During development, LAMP is expressed on growing axons, growth cones, and their target neurons, but in adults it is restricted to membranes of somata and dendrites. In the adult spinal cord, LAMP immunoreactivity is found only on neurons of lamina II, lamina X, and the intermediolateral cell column and its ultrastructural localization is entirely postsynaptic. We studied changes in the expression of LAMP in lamina II of adult rat spinal cord after L1-S2 dorsal rhizotomy, a procedure that partially deafferents lamina II neurons and induces axonal sprouting by spared systems in lamina II. At the light microscopic level, LAMP immunoreactivity in lamina II was decreased in density at 3, 10, and 60 days postoperatively. This decrease in immunoreactivity suggests that LAMP expression by lamina II neurons may normally be regulated by specific afferent activity. Ultrastructurally, in control lamina II and after deafferentation in both control and deafferented lamina II at 3 and 60 days postoperatively, LAMP expression was restricted to postsynaptic membranes. Ten days after deafferentation, however, when axons are actively sprouting, LAMP was expressed on both axonal and postsynaptic membranes. The reexpression of LAMP on axonal profiles after deafferentation may identify axons that undergo sprouting in response to deafferentation.

Afferent Pathways

NK1, NMDA, 5HT1a, and 5HT2 receptor binding sites in the rat lumbar spinal cord: modulation following sciatic nerve crush.

Quantitative receptor binding autoradiography was used to study the NK1, NMDA, 5HT1a, and 5HT2 receptor binding densities in the adult rat lumbar spinal cord from 3 days to 20 weeks following a unilateral crush lesion of the sciatic nerve. NK1 binding density increased unilaterally in the superficial dorsal horn on the side of the sciatic crush to reach levels 60% above controls by 4 weeks following the lesion and returned to control values by 12 weeks. NMDA binding density increased bilaterally and equally in both the dorsal and ventral horns to reach 300% of control values at 2 weeks following the crush and returned to near control values by 20 weeks following the lesion. Serotonergic receptor binding did not change. The changes in NK1 receptor binding density on postsynaptic dorsal horn cells are consistent with a response to the decrease and recovery in the synthesis and transport of tachykinins by the dorsal root ganglion cells following peripheral nerve injury. the bilateral changes in NMDA receptor binding are more likely mediated by polysynaptic pathways in the spinal cord that respond to the changes in metabolic events of the dorsal root ganglion cells evoked by axotomy and regeneration.

Animals

Long-chain alkenes of the haptophytes Isochrysis galbana and Emiliania huxleyi.

The major alkenes of the haptophytes Isochrysis galbana (strain CCAP 927/14) and Emiliania huxleyi (strains CCAP 920/2 and VAN 556) have been identified by nuclear magnetic resonance spectroscopy and by mass spectrometric analysis of their dimethyl disulfide adducts. The dominant alkene in I. galbana is (22Z)-1 ,22-hentriacontadiene, with 1,24-hentriacontadiene and 1,24-tritriacontadiene present in much lower abundance; (22Z)-1,22-hentriacontadiene also occurs in E. huxleyi (strain CCAP 920/2), together with (2Z,22Z)-2,22-hentriacontadliene (the major hydrocarbon) and (3Z,22Z)-3,22-hentriacontadiene. Minor abundances of 2,24-hentriacontadiene and 2,24-tritriacontadiene are also present in this strain. In contrast, the dominant alkene in E. huxleyi (strain VAN 556) is (15 E,22E)-1,16,23-heptatriacontatriene with the related alkatriene 1,15,22-octatriacontatriene also present and (22Z)-1,22-hentriacontadiene occurring as a minor component. From structural relationships (15E,22E)-1,15,22-heptatriacontatriene is proposed to derive from the same biosynthetic pathway as that of the characteristic C37 alkenones which occur in both E. huxleyi and I. galbana. The C31 and C33 dienes likely derive from chain extension and decarboxylation of (Z)-9-octadecenoic acid or (Z)-7-hexadecenoic acid, using a pathway analogous to that elucidated previously in the chlorophyte Botryococcus braunii. Therefore, long-chain dienes and trienes, which can co-occur in haptophytes, may have distinct biosynthetic pathways.

Alkenes

Health-related quality of life assessment in euthymic and depressed patients with bipolar disorder. Psychometric performance of four self-report measures.

The purpose of this study was to evaluate the psychometric properties of selected health-related quality of life (HRQL) self-report measures in 62 euthymic and depressed patients diagnosed with bipolar disorder. Patients completed the Quality of Life in Depression Scale (QLDS), Mental Health Index-17 (MHI-17), Cognitive Function Scale, and Medical Outcomes Study Short Form-36 (SF-36) at baseline and 8 weeks following treatment. Hamilton and Young Rating Scales were used to assess clinical status and validate the HRQL measures. The MHI-17, Cognitive Function Scale, QLDS, and SF-36 social function, vitality, role limitations-emotional, and mental health scales have good reliability and validity, and are responsive to changes in clinical status in patients with bipolar disorder. Although the small sample size limits generalizablity, euthymic and depressed outpatients with bipolar disorder appear to contribute reliable self reports on selected aspects of their quality of life.

Adult

Objective interpretation of bovine clinical biochemistry data: application of Bayes law to a database model.

With the advent of animal-side biochemistry analysers in veterinary practice, the requirement for ready access to reliable means for interpretation of the results is of increasing importance. At the University of Glasgow Veterinary School (GUVS), a large computerised hospital database containing extensive clinical, laboratory, and pathological information has been maintained. A retrospective study was undertaken to investigate plasma biochemistry results and corresponding post mortem diagnosis data from 754 unwell cattle which had presented to GUVS over the study period. Initial analysis of the clinical biochemistry data from this unwell population revealed that the parameters did not follow a normal distribution. This finding suggested that the accepted reference range method for the interpretation of clinical biochemistry data may provide limited information about the unwell animal. By applying a combination of percentile analysis and conditional probability techniques to the hospital data, the development of a means of clinical biochemistry interpretation was developed whereby a clinician could determine whether a value was abnormal, the degree of abnormality, and the most likely associated diseases. For example, a urea value of 30 mmol/l lay within the top 5% of results, and one of the most common diseases associated with this urea value was pyelonephritis. Furthermore, a Bayesian approach allowed the quantification of the relationship between any plasma biochemistry value and disease through the generation of a ratio termed the 'biochemical factor'. Using the same example, given a urea value of 30 mmol/l, pyelonephritis was eight times more likely than before any biochemistry information was known. The results from the study were used to form the basis of a software system which may ultimately be used by the clinical to aid in the recognition, treatment and prevention of disease in the veterinary domain.

Animals

Susceptibility to trypanosomosis of three Bos indicus cattle breeds in areas of differing tsetse fly challenge.

Studies to assess the differences in susceptibility to trypanosomosis among Bos indicus cattle breeds (Maasai Zebu, Orma Boran and Galana Boran) were conducted under conditions of varying tsetse fly challenge at the Nguruman escarpment in south-western Kenya, for a period of 1 year. It was found that under tsetse challenge quantified as high, Maasai Zebu and Orma Boran were less susceptible than Galana Boran to trypanosome infections, as judged by the significantly lower incidence of infection, development of less severe anaemia, fewer requirements for trypanocidal drug treatments, higher growth rates and fewer mortalities. In the area where tsetse challenge was considered low as a result of a tsetse fly control operation using odour-baited traps, only the Maasai Zebu and Orma Boran were compared. No significant differences in the incidence of infection, degree of anaemia or growth rates were observed between the two breeds, but all were significantly different from their counterparts in the high tsetse challenge area. These results suggest that there is variation in resistance to trypanosomosis among Bos indicus cattle breeds that could be exploited as part of the integrated trypanosomosis control programmes in East Africa.

Anemia

The relative accuracy of mercury, Tempa-DOT and FeverScan thermometers.

This project aimed to assess the accuracy of Tempa-DOT and FeverScan for measuring children's temperatures. Tempa-DOT is a small flat chemical thermometer with 50 dots that change colour at specific temperatures. FeverScan is a liquid crystal strip thermometer with temperature sensitive colour bars that change colour when held against the forehead. Two medical students undertook this study in a hospital in Zambia. They saw most children presented to the hospital over a six-week period and on the children's ward. A mercury thermometer was placed in one axilla, a Tempa-DOT thermometer in the other, and the FeverScan was held on the child's forehead. Data were obtained from 1090 children with a median age of two years. The sensitivity of FeverScan to correctly identify febrile children was 89% and the positive predictive value to detect a fever was 57%. The sensitivity of Tempa-DOT to correctly identify febrile children was 92% and the positive predictive value for detecting febrile children was 86%. Tempa-DOT has a much better predictive value than FeverScan for detecting fever.

Adolescent

The influence of dietary supplementation with urea on resilience and resistance to infection with Haemonchus contortus.

Previous research has indicated that supplementing an apparently adequate diet with additional protein improves both host resistance and resilience in lambs infected with Haemonchus contortus. The present study tested the influence of supplementation with non-protein nitrogen (urea). Helminth-naive Hampshire Down lambs were given an apparently adequate basal diet or a diet supplemented with urea. The lambs were then infected with Haemonchus contortus for 10 weeks. Supplementation with urea had no discernible effect on resistance to infection; faecal egg counts, worm burdens, worm lengths and mean number of eggs per adult female worm did not differ between the 2 groups. However, lambs on the supplemented diet showed better resilience; they had greater packed red cell volumes, higher plasma albumin concentrations and increased liveweight gain compared to lambs on the basal diet. The loss of appetite following infection was less in lambs fed the urea-supplemented diet. The observed effect of urea supplementation was seemingly due to greater food consumption as well as the better diet.

Animal Nutritional Physiological Phenomena

Activated protein C resistance, thrombophilia, and inflammatory bowel disease.

Thromboembolic events frequently complicate the clinical course of patients with inflammatory bowel disease (IBD). Hereditary thrombophilia may contribute to this tendency. Resistance to activated protein C is the most recently described thrombophilic state and may account for up to 40% of patients with thrombophilia. Thirty-seven patients with IBD were studied (mean age 44 years, range 18-82 years). Three patients had a history of thrombotic episodes. The 37 controls included 23 men and 17 women (mean age 48 years, range 16-89 years). Disease activity was assessed using the Harvey Bradshaw index for patients with Crohn's disease and the Truelove and Witts grading system for patients with ulcerative colitis. Levels of fibrinogen, antithrombin III (ATIII), protein C, protein S, activated protein C resistance (APCR), and the presence of a lupus anticoagulant (LA) were determined. Median ATIII levels in patients with IBD were significantly lower than controls (98% vs 106%, P = 0.007), while fibrinogen was elevated (4.2 vs 3.3 g/liter, P = 0.026) despite quiescent disease activity. LA was detected in 7/37 patients in the IBD group compared to 0/37 controls. (chi2 = 5.68, P = 0.017). No significant difference was observed in levels of inherited thrombophilic factors and in particular APCR between IBD patients and controls. In conclusion, the presence of inherited thrombophilic defects, in particular APCR, is uncommon in patients with IBD and does not merit routine screening.

Adolescent

Comparison of tacrolimus absorption in transplant patients receiving continuous versus interrupted enteral nutritional feeding.

OBJECTIVE: To determine the effect of enteral nutritional feeding on the absorption of tacrolimus administered through a nasoduodenal tube to organ transplant patients. METHODS: A nonrandomized, prospective study of tacrolimus absorption was performed in 10 liver or lung transplant patients who received Osmolite enteral nutrition through a nasoduodenal feeding tube. Multiple blood samples were collected just prior to and at 30 minutes, 1, 2, 3, 4, 6, 8, 10, and 12 hours after nasoduodenal administration of tacrolimus on 2 consecutive days, once when tacrolimus was administered along with the continuous enteral feeding and the other time when the enteral feeding was withheld 1 hour prior to and 8 hours after tacrolimus administration, to assess tacrolimus absorption. The whole blood tacrolimus concentrations were measured by the microparticulate enzyme immunoassay method. Pharmacokinetic parameters between the two time periods were compared by using a paired t-test at a significance level of a p value of 0.05 or less. RESULTS: The time to reach peak blood concentrations (p = 0.055), dose-normalized trough concentrations (p = 0.617), maximum blood concentrations (p = 0.197), and dose-normalized AUC (p = 0.755) were not significantly different between two study periods. CONCLUSIONS: This study demonstrated that simultaneous administration of Osmolite enteral feedings with tacrolimus did not interfere with tacrolimus absorption in transplant patients.

Absorption

Trypanotolerance, an option for sustainable livestock production in areas at risk from trypanosomosis.

Trypanosomosis is one of the major constraints on animal production in areas of Africa which have the greatest potential for significant increases in domestic livestock populations and livestock productivity. While the eradication of trypanosomosis from the entire continent is an unrealistic goal, considerable effort has been invested in the control of this disease through the use of trypanocidal drugs, management of the vector and exploitation of the genetic resistance exhibited by indigenous breeds. There is little hope that a conventional, anti-infection vaccine will be produced in the near future. Drug resistance is developing faster than generally thought. The control of the tsetse fly has been attempted over many decades. The decreasing efficacy of available trypanocidal drugs and the difficulties of sustaining tsetse control increase the imperative need to enhance trypanotolerance through selective breeding, either within breeds or through cross-breeding. Trypanotolerance has been defined as the relative capacity of an animal to control the development of the parasites and to limit their pathological effects, the most prominent of which is anaemia. A major constraint on selection for trypanotolerance in cattle, for both within-breed and cross-breeding programmes, has been the absence of practical reliable markers of resistance or susceptibility. Distinct humoral immune response to trypanosome infection is the major feature of bovine trypanotolerance. The role that these responses play in the control of infection or disease is being addressed by ongoing research, but remains a matter of speculation at present. Results in recent years have shown that packed cell volume (PCV) in particular and parasitaemia, the two principal indicators of trypanotolerance, are strongly correlated to animal performance. However, although direct effects of trypanosome infections on PCV and growth are obvious, more sensitive diagnostic methods for reflecting parasite control are required so that individual animals can be categorised reliably for their parasite control capability. One key finding is the major contribution made by each of the indicators evaluated to the overall trypanotolerance variance. Preliminary genetic parameters for PCV provide evidence that trypanotolerance is not only a breed characteristic but is also a heritable trait within the N'Dama population; this brings new opportunities for improved productivity through selection for trypanotolerance. More reliable estimation of genetic parameters of the indicators may well show that these parameters must be handled simultaneously for optimal progress. This would require diagnostics for assessing parasite control capability that identify trypanosome species more accurately, especially in mixed infections. A major advantage of trypanotolerant livestock, particularly N'Dama cattle, is the resistance or adaptation of this breed to many of the important pathogenes which prevail in the sub-humid and humid tropics. Research on practical indicators of resistance to these conditions will be required to establish relevant integrated strategies based on disease-resistant livestock. Selective breeding will require the integration of the traits that farmers hold important for their production systems.

Africa

Effect of domperidone on the health-related quality of life of patients with symptoms of diabetic gastroparesis.

OBJECTIVE: To describe the health-related quality of life (HRQOL) of patients with insulin-treated diabetes and symptoms of diabetic gastroparesis and to assess the impact of domperidone on HRQOL in these patients. RESEARCH DESIGN AND METHODS: This two-phase multicenter study was part of a safety and efficacy investigation. Phase I involved 4-week single-blind treatment with domperidone 20 mg q.i.d. (n=269). Patients demonstrating significant symptomatic improvement (n=208) continued to phase 11, a 4-week, double-blind, parallel-group study with patients receiving placebo (n=103) or domperidone (n=105). Patients completed the Medical Outcomes Study Short-Form-36 Health Survey at selection and at the end of each phase. Physical component summary (PCS) and mental component summary (MCS) scores served as primary parameters, and the eight subscales were secondary parameters. RESULTS: HRQOL scores of subjects enrolled in the trial were significantly lower than norms from the general population and people with diabetes (P < 0.001). Subjects experiencing symptomatic improvement after 4 weeks of single-blind treatment demonstrated significant improvement in all HRQOL parameters (P < 0.001); PCS, MCS, and six subscale scores of nonresponders did not change. Between-group change score differences were significant for PCS, MCS, and seven subscales (P < 0.05 to P < 0.001). During phase II, the domperidone group maintained their HRQOL; the placebo group showed a significant decline in PCS and four subscales (P < 0.05). The between-group difference in the PCS score change was statistically significant (-1.77 vs. 0.65, P=0.05). CONCLUSIONS: Results suggest that patients with symptoms of diabetic gastroparesis experience notable HRQOL impairment and that symptomatic relief with domperidone is accompanied by improvements in HRQOL that can be sustained over 4 weeks of treatment.

Adult

A compass for customer needs.

Baldor Electric uses a tool it calls the value formula to help teach its employees to look at their work through the eyes of the customer. In fact, the goal of the value improvement process is to focus everyone on customer value, and the employees, by going through five training courses, learn how improving quality and service and reducing cost and time lead to higher value for the customer.

Consumer Behavior

Assessing a VR-based learning environment for anatomy education.

The purpose of the research proposed herein is to develop an empirical, methodological tool for the assessment of visual depth perception in virtual environments (VEs). Our goal is to develop and employ a behaviorally-based method for assessing the impact of VE design features on the perception of visual depth as indexed by the performance of fundamental perceptual-motor activities. Specifically, in this experiment we will assess the affect of two dimensions of VE system design--(1) viewing condition or "level of immersion", and (2) layout/design of the VE--on the performance of an engaging, game-like task. The characteristics of the task to be employed are as follows--(1) it places no demands on cognition in the form of problem solving, retrieval of previously learned information, or other analytic activity in order to assure that (2) variations in task performance can be exclusively attributed to the extent to which the experimental factors influence visual depth perception. Subjects' performance will be assessed in terms of the speed and accuracy of task performance, as well as underlying dimensions of performance such as workload, fatigue, and physiological well being (i.e., cybersickness). The results of this experiment will provide important information on the effect of VE immersion and other VE design issues on human perception and performance. Further development, refinement, and validation of this behaviorally-based methodology will be pursued to provide user-centered design criteria for the design and use of VE systems.

Anatomy