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Biomedical subjects

A Roberts

Publications and source records attributed to A Roberts.

At least 91 records · Page 5Linked to original sources

An audit of clinical nurse practitioner led thrombolysis to improve the treatment of acute myocardial infarction.

BACKGROUND: The aim of the study was to audit the impact of cardiac nurse practitioner led thrombolysis as a method of reducing call to needle times for acute myocardial infarction (AMI) in a single district hospital. METHODS: This was a prospectively planned, observational study, comparing time delay between arrival at hospital and the administration of thrombolysis ('door to needle' time) in patients presenting with AMI in a district general hospital serving a population of 270000. The 6 months before and 6 months after initiation of the scheme were compared. RESULTS: There were 151 consecutive patients (undergoing 163 thrombolysis episodes). The median door to needle time fell from 60 min (range 42-110 min) to 30 min (range 20-61 min) (p<0.01). In those patients eligible for immediate thrombolysis the number of cases treated within 30 min of arrival rose from 10/58 (17 per cent) to 48/64 (75 per cent) (p<0.01). The proportion of cases where there was an initial delay as a result of non-diagnostic ECG or possible contra-indication to therapy remained constant, 20/78 (25 per cent) cases before and 21/85 (25 per cent) cases after initiation of the scheme. The number of cases of inappropriate thrombolysis fell from 73 per cent to 30 per cent. CONCLUSION: The provision of i.v. thrombolysis by cardiac nurse practitioners is safe and should be considered as a method for achieving acceptable door to needle times in the management of acute myocardial infarction.

Aged↗

Glycoprotein exchange vectors based on vesicular stomatitis virus allow effective boosting and generation of neutralizing antibodies to a primary isolate of human immunodeficiency virus type 1.

Live recombinant vesicular stomatitis viruses (VSVs) expressing foreign antigens are highly effective vaccine vectors. However, these vectors induce high-titer neutralizing antibody directed at the single VSV glycoprotein (G), and this antibody alone can prevent reinfection and boosting with the same vector. To determine if efficient boosting could be achieved by changing the G protein of the vector, we have developed two new recombinant VSV vectors based on the VSV Indiana serotype but with the G protein gene replaced with G genes from two other VSV serotypes, New Jersey and Chandipura. These G protein exchange vectors grew to titers equivalent to wild-type VSV and induced similar neutralizing titers to themselves but no cross-neutralizing antibodies to the other two serotypes. The effectiveness of these recombinant VSV vectors was illustrated in experiments in which sequential boosting of mice with the three vectors, all encoding the same primary human immunodeficiency virus (HIV) envelope protein, gave a fourfold increase in antibody titer to an oligomeric HIV envelope compared with the response in animals receiving the same vector three times. In addition, only the animals boosted with the exchange vectors produced antibodies neutralizing the autologous HIV primary isolate. These VSV envelope exchange vectors have potential as vaccines in immunizations when boosting of immune responses may be essential.

AIDS Vaccines↗

Circadian rhythms of body temperature and activity levels during 63 h of hypoxia in the rat.

The hypothermic response of rats to only brief ( approximately 2 h) hypoxia has been described previously. The present study analyzes the hypothermic response in rats, as well as level of activity (L(a)), to prolonged (63 h) hypoxia at rat thermoneutral temperature (29 degrees C). Mini Mitter transmitters were implanted in the abdomens of 10 adult Sprague-Dawley rats to continuously record body temperature (T(b)) and L(a). After habituation for 7 days to 29 degrees C and 12:12-h dark-light cycles, 48 h of baseline data were acquired from six control and four experimental rats. The mean T(b) for the group oscillated from a nocturnal peak of 38.4 +/- 0.18 degrees C (SD) to a diurnal nadir of 36.7 +/- 0.15 degrees C. Then the experimental group was switched to 10% O(2) in N(2). The immediate T(b) response, phase I, was a disappearance of circadian rhythm and a fall in T(b) to 36.3 +/- 0.52 degrees C. In phase II, T(b) increased to a peak of 38.7 +/- 0.64 degrees C. In phase III, T(b) gradually decreased. At reoxygenation at the end of the hypoxic period, phase IV, T(b) increased 1.1 +/- 0.25 degrees C. Before hypoxia, L(a) decreased 70% from its nocturnal peak to its diurnal nadir and was entrained with T(b). With hypoxia L(a) decreased in phase I to essential quiescence by phase II. L(a) had returned, but only to a low level in phase III, and was devoid of any circadian rhythm. L(a) resumed its circadian rhythm on reoxygenation. We conclude that 63 h of sustained hypoxia 1) completely disrupts the circadian rhythms of both T(b) and L(a) throughout the hypoxic exposure, 2) the hypoxia-induced changes in T(b) and L(a) are independent of each other and of the circadian clock, and 3) the T(b) response to hypoxia at thermoneutrality has several phases and includes both hypothermic and hyperthermic components.

Activity Cycles↗

Responses of young Xenopus laevis tadpoles to light dimming: possible roles for the pineal eye.

When the light is dimmed, the pineal eye of hatchling Xenopus laevis tadpoles excites the central pattern generator for swimming, but the behavioural significance of pineal excitation is unclear. We show that tadpoles spend 99 % of their time hanging from the surface meniscus or solid objects using mucus secreted by a cement gland on the head. Attachment inhibits swimming, but unattached tadpoles swim spontaneously. Provided that their pineal eye is intact, they attach closer to the water surface in the dark than in the light and attach preferentially to the underside of floating objects that cast shadows. Dimming causes tadpoles swimming horizontally to turn upwards and is very effective in initiating upward swimming in unattached tadpoles. Similar pineal-dependent responses during swimming are present up to stage 44. Pinealectomy blocks responses to dimming at all stages. Recordings from immobilised tadpoles reveal that light dimming induces faster fictive swimming and that pineal activity is increased for up to 20 min during sustained light dimming. We suggest that the increase in pineal discharge during dimming increases the probability of upward swimming and, in this way, increases the probability of tadpoles attaching to objects higher in the water column that cast shadows.

Aging↗

Simple mechanisms organise orientation of escape swimming in embryos and hatchling tadpoles of Xenopus laevis.

Many amphibian tadpoles hatch and swim before their inner ears and sense of spatial orientation differentiate. We describe upward and downward swimming responses in hatchling Xenopus laevis tadpoles from stages 32 to 37/38 in which the body rotates about its longitudinal axis. Tadpoles are heavier than water and, if touched while lying on the substratum, they reliably swim upwards, often in a tight spiral. This response has been observed using stroboscopic photography and high-speed video recordings. The sense of the spiral is not fixed for individual tadpoles. In 'more horizontal swimming' (i.e. in directions within +/-30 degrees of the horizontal), the tadpoles usually swim belly-down, but this position is not a prerequisite for subsequent upward spiral swimming. Newly hatched tadpoles spend 99 % of their time hanging tail-down from mucus secreted by a cement gland on the head. When suspended in mid-water by a mucus strand, tadpoles from stage 31 to 37/38 tend to swim spirally down when touched on the head and up when touched on the tail. The three-dimensional swimming paths of stage 33/34 tadpoles were plotted using simultaneous video images recorded from the side and from above. Tadpoles spiralled for 70 % of the swimming time, and the probability of spiralling increased to 1 as swim path angles became more vertical. Tadpoles were neutrally buoyant in Percoll/water mixtures at 1.05 g cm(-)(3), in which anaesthetised tadpoles floated belly-down and head-up at 30 degrees. In water, their centre of mass was ventral to the muscles in the yolk mass. A simple mathematical model suggests that the orientation of tadpoles during swimming is governed by the action of two torques, one of which raises the head (i.e. increases the pitch) and the other rotates (rolls) the body. Consequently, tadpoles (i) swim belly-down when the body is approximately horizontal because the body is ballasted by dense yolk, and (ii) swim spirally at more vertical orientations when the ballasting no longer stabilises orientation. Measurements in tethered tadpoles show that dorsal body flexion, which could produce a dorsal pitch torque, is present during swimming and increases with tailbeat frequency. We discuss how much of the tadpole's behaviour can be explained by our mathematical model and suggest that, at this stage of development, oriented swimming responses may depend on simple touch reflexes, the organisation of the muscles and physical features of the body, rather than on vestibular reflexes.

Animals↗

Improved blood cellular biocompatibility with heparin coated circuits during cardiopulmonary bypass.

BACKGROUND: The clinical use of heparinized surfaces in the extracorporeal circuit was studied to find out if there was any blood cell rheologic benefit to support its use in routine low risk cardiac surgery. METHODS: In a prospective single blind study, 39 patients were operated upon with the heart lung machine for angina pectoris by coronary bypass grafting and were randomized to a control group or a heparin group. Blood cell rheology was analysed using the St. George filtrometer where damage to the red blood cells and white blood cells was estimated by assessing deformability reductions, transit, time increases and clogging rate and clogging particle changes. RESULTS: At the end of cardiopulmonary bypass, in the heparin group, the red cell filterability (rFR) and the white cell filterability (WFR) were 8% better than in the control group (p=0.0079 and p=0.027 respectively). The red cell transit time was 19% slower in the control group (p=0.0351). The red cell clogging rate (RCR) and clogging particles (RCP) were significantly lower in the heparin group (p=0.0212 and p=0.0409 respectively. The white cell clogging rate (WCR) and clogging particles (WCP) showed a similar pattern. CONCLUSIONS: In spite of these significant differences the clinical outcome was similar in the groups. Thus heparin coating of the extracorporeal circuit reduces blood cell rheologic damage significantly in low risk patients undergoing routine bypass surgery for angina but this use did not lead to any clinical benefit postoperatively. Therefore the use of such circuits for routine low risk cardiac surgery cannot be recommended.

Aged↗

NLP techniques associated with the OpenGALEN ontology for semi-automatic textual extraction of medical knowledge: abstracting and mapping equivalent linguistic and logical constructs.

This research project presents methodological and theoretical issues related to the inter-relationship between linguistic and conceptual semantics, analysing the results obtained by the application of a NLP parser to a set of radiology reports. Our objective is to define a technique for associating linguistic methods with domain specific ontologies for semi-automatic extraction of intermediate representation (IR) information formats and medical ontological knowledge from clinical texts. We have applied the Edinburgh LTG natural language parser to 2810 clinical narratives describing radiology procedures. In a second step, we have used medical expertise and ontology formalism for identification of semantic structures and abstraction of IR schemas related to the processed texts. These IR schemas are an association of linguistic and conceptual knowledge, based on their semantic contents. This methodology aims to contribute to the elaboration of models relating linguistic and logical constructs based on empirical data analysis. Advance in this field might lead to the development of computational techniques for automatic enrichment of medical ontologies from real clinical environments, using descriptive knowledge implicit in large text corpora sources.

Electronic Data Processing↗

Having our cake and eating it too: how the GALEN Intermediate Representation reconciles internal complexity with users' requirements for appropriateness and simplicity.

Clinical terminologies are complex objects, getting more complex as the requirements on them grow, and as more complex technologies are used in their construction. But to the clinical end-user, functionality and utility is important, not inherent complexity--the simpler a clinical terminology can be for the end-user, the better. To reconcile these contradictory requirements, the GALEN Programme has developed an Intermediate Representation that allows the OpenGALEN Clinical Terminology to retain a high degree of internal complexity, whilst allowing it to be efficiently maintained, and easily used. This paper describes the elements of the Intermediate Representation, how it works, and some experience of its use.

Abstracting and Indexing↗

Motoneurons of the axial swimming muscles in hatchling Xenopus tadpoles: features, distribution, and central synapses.

Xenopus tadpole motoneurons make cholinergic synapses within the spinal cord. This excitation changes with longitudinal position and contributes to the excitation that controls motor activity and its longitudinal spread during swimming. To explore the anatomic constraints on this excitation, backfilling has been used to examine the anatomy and distribution of the whole population of spinal motoneurons, to define the extent of their central axons and to find where they make synapses. Motoneuron features show considerable variation but do not allow their separation into primary and secondary. Most motoneurons have descending central axons and it is likely that central synapses are made from these axons as longitudinal dendritic extent is very limited. Motoneuron density reaches a broad plateau over the mid-trunk region at 12-13 per 100 microm. Soma size does not change with longitudinal position, but the dorsoventral extent of the dendrites decreases caudally, whereas the central axon length increases. Motoneuron distribution data were used to estimate the longitudinal distribution of central motoneuron axons. This has a broad plateau at 12-14 per 100 microm over much of the trunk and only decreases significantly caudal to the anus. This distribution correlates with cholinergic excitation during swimming. Transmission electron microscopy of motoneurons backfilled with horseradish peroxidase was used to show that central motoneuron axons make en passant synapses with motoneuron dendrites and the dendrites of other unstained neurons. By using measures of synapse frequency and total dendrite length, trunk motoneurons are estimated to each receive 100-200 synapses.

Acetylcholine↗

Teaching hospitals. University challenge.

The position of large teaching hospitals in the NHS is being challenged by changing patterns of medical education and the expansion of services offered by acute hospitals. The clinical activity of teaching hospitals is now similar to that of district general hospitals. The future of teaching hospitals may lie in becoming centres of research excellence.

Clinical Clerkship↗

Role of elevated plasma transforming growth factor-beta1 levels in wound healing.

Transforming growth factor (TGF)-beta1 plays a central role in wound healing. Wounds treated with neutralizing antibody to TGF-beta1 have a lower inflammatory response, reduced early extracellular matrix deposition, and reduced later cutaneous scarring, indicating the importance of local tissue TGF-beta1. By contrast, increasing the local, tissue levels of TGF-beta1 increases the early extracellular matrix deposition but does not alter scar formation. Increased levels of plasma TGF-beta1 correlate with increased fibrogenesis in the lung, kidneys, and liver. The aim of the present study was to investigate the role of elevated systemic levels of TGF-beta1 on wound healing. We used transgenic mice that express high levels of active TGF-beta1 and have elevated plasma levels of TGF-beta1 and wild-type mice of the same strain as controls. Incisional wounds and subcutaneously implanted polyvinyl alcohol (PVA) sponges were analyzed. Surprisingly, cutaneous wounds in transgenic, TGF-beta1-overexpressing mice healed with reduced scarring accompanied by an increase in the immunostaining for TGF-beta3 and TGF-beta-receptor RII and a decrease in immunostaining for TGF-beta1 compared with wounds in control mice. By contrast, the PVA sponges showed the opposite response, with PVA sponges from transgenic mice demonstrating an enhanced rate of cellular influx and matrix deposition into the sponges accompanied by an increase in the immunostaining for all three TGF-beta isoforms and their receptors compared with PVA sponges from control mice. Together, the data demonstrate that increased circulating levels of TGF-beta1 do not always result in increased expression or activity in selected target tissues such as the skin. The two wound models, subcutaneously implanted PVA sponges and cutaneous incisional wounds, differ significantly in terms of host response patterns. Finally, the data reinforce our previous observations that the relative ratios of the three TGF-beta isoforms is critical for control of scarring.

Animals↗

Liver function tests and glucose and lipid metabolism in growth-restricted fetuses.

OBJECTIVE: To assess hematologic and biochemical blood variables in growth-restricted fetuses and relate them to biophysical measurements. METHODS: Blood was sampled from 22 growth-restricted fetuses. All had normal karyotypes and no congenital infections. Venous pH, partial pressure of oxygen, hematocrit, glucose, uric acid, urea, creatinine, total protein, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase, creatinine kinase, triglycerides, and cholesterol were measured and compared with our reference range. RESULTS: Ultrasound measurements of abdominal circumference correlated with fetal pH (r = 0.64), partial pressure of oxygen (r = 0.52), glucose (r = 0.67), total bilirubin (r = -0.54), lactic dehydrogenase (r = -0.48), and triglyceride levels (r = -0.65). Compared with fetuses with present end-diastolic velocities in the umbilical artery, the eight with absent end-diastolic velocities had lower pH (median z score -4.31), partial pressure of oxygen (median z score = -2.39), glucose (median z score = -2.01), and cholesterol (median z score = -2.34), and higher gamma-glutamyltransferase (median z score = 2.43), lactic dehydrogenase (median z score = 3.75), urea (median z score = 1.33), creatinine (median z score = 1.23), and triglyceride levels (median z score = 1.71). Only triglycerides correlated with abdominal circumference, independent of Doppler results. CONCLUSION: Growth-restricted fetuses with absent end-diastolic velocities in the umbilical artery had more marked acidemia, hypoxemia, hypoglycemia, and abnormal liver function than those with end-diastolic velocities. Triglyceride levels were inversely related to fetal size independent of Doppler results. High triglyceride levels might reset fetal homeostatic mechanisms, leading to disturbances of lipid metabolism in later life.

Acid-Base Equilibrium↗