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Biomedical subjects

D M Taylor

Publications and source records attributed to D M Taylor.

At least 19 recordsLinked to original sources
PubMed2006

Inactivation of transmissible spongiform encephalopathy agents during the manufacture of dicalcium phosphate from bone.

Dicalcium phosphate was prepared from industrial crushed bone artificially contaminated with transmissible spongiform encephalopathy agents in two experiments carried out in an accurately scaled-down laboratory model of the industrial manufacturing process. In one experiment, 10 g of mouse brain infected with the 301V strain of mouse-passaged bovine spongiform encephalopathy agent was added to the crushed bone; in the other experiment, 10 g of hamster brain infected with the 263K strain of hamster-passaged scrapie agent was added. Samples of the infectious brain and dried dicalcium phosphate were assayed for the amount of 301V or 263K infectivity present. The titre of infectivity of the 301V-infected brain was 10(7.7) intracerebral ID50/g; that of the 263K-infected brain was 10(8.0) intracerebral ID50/g. The titres of the dried samples of dicalcium phosphate were 10(2.5) ID50/g in the experiment spiked with 301V and 10(2.7) ID50/g in the experiment spiked with 263K. The calculated clearance factors were 10(3.9) for the experiment with 301V and 10(3.8) for the experiment with 263K.

Animal Feed↗
PubMed2006

Health resource utilization associated with switching to risperidone long-acting injection.

OBJECTIVE: Studies have shown oral risperidone and conventional depot antipsychotics decrease direct healthcare costs largely by reducing hospitalization. Our aim was to assess the effect on bed stay of risperidone injection prescribed in normal clinical practice. METHOD: Patients prescribed risperidone long-acting injection (RLAI) were identified and followed-up for 1 year. Resource use data were collected for 3 years before and for 1 year after the initiation of RLAI. The main outcome measure was bed stay before and after the prescription of RLAI. RESULTS: Outcome data were available for 250 subjects. Eighty-one subjects (32.4%) completed 1 year's treatment. Days spent in hospital increased from (mean number/patient) 31 in year -3 to 44 in year -2 to 90 in year -1 to 141 in year +1. Direct healthcare costs increased accordingly. Outcome for RLAI continuers was similar to that of discontinuers. CONCLUSION: Switching to RLAI was associated with a continuation of the trend for increased bed stay and use of healthcare resources.

Administration, Oral↗
PubMed2005

Inactivation of the BSE agent by the heat and pressure process for manufacturing gelatine.

Dietary exposure to the bovine spongiform encephalopathy (BSE) agent is the probable cause of variant Creutzfeldt-Jakob disease in people. The industrial manufacturing process for the production of gelatine and colloidal protein by the heat and pressure process was downscaled accurately and its capacity to remove or inactivate bse infectivity was investigated. Gelatine was made from bones experimentally contaminated with mouse brain infected with the 301V strain of mouse-passaged bse agent in which the infective titre was 10(8.7) ID50/g. No infectivity was detected in the extracted protein (> or =10(0.45) ID50/g), and the calculated clearance factor was 10(6.5) ID50 or more.

Animals↗
PubMed2005

Phase locking and supermode selection in multicore photonic crystal fiber lasers with a large doped area.

We report on the laser properties of multicore photonic crystal fiber lasers. A stable phase locking of six- and seven-core structures through evanescent coupling is observed. Effective supermode selection is obtained by using both diffraction losses and the Talbot effect. A pure in-phase supermode is obtained (1.1 times diffraction limited). The laser operating in this mode has a slope efficiency of 70% with up to 44 W of output power. The modal area of the in-phase supermode multicore fiber is 1150 microm2, which makes it, to our knowledge, the single-mode fiber laser with the largest mode field area. In-phase laser action is stable when the fiber is bent.

Journal Article↗
PubMed2005

Treatment of accidental intakes of plutonium and americium: guidance notes.

The scientific basis for the treatment of the contamination of the human body by plutonium, americium and other actinides is reviewed. Guidance Notes are presented for the assistance of physicians and others who may be called upon to treat workers or members of the public who may become contaminated internally with inhaled plutonium nitrate, plutonium tributyl phosphate, americium nitrate or americium oxide.

Americium↗
PubMed2005

Aripiprazole in schizophrenia: consensus guidelines.

Schizophrenia is a chronic disabling disease which in the majority of cases requires long-term treatment with antipsychotic medication. Before the development of atypical antipsychotics, treatment choice was restricted to conventional (or typical) antipsychotics, which are known to cause a range of side effects including extrapyramidal symptoms. Although atypical agents provide a favourable alternative (advocated by the National Institute of Clinical Excellence in the UK), they are associated with side effects. These differ between agents, but can include weight gain, sedation and hyperprolactinaemia. Aripiprazole is a newly available atypical antipsychotic for the treatment of schizophrenia. With the apparent imitations of currently available medications, aripiprazole provides clinicians with another treatment option. The purpose of these guidelines is to outline the consensus reached by the Schizophrenia Innovation Working Group on best practice in prescribing and appropriate use of aripiprazole in the UK.

Antipsychotic Agents↗
PubMed2004

Radionuclide biokinetics database (RBDATA-EULEP): an update.

The main activity of the RBDATA-EULEP project is the development of an electronic database of information on the biokinetics of radionuclides after intake by inhalation, ingestion or injection. It consists of linked tables of publications and experiments, with details and comments on the materials, procedures and results. By March 2004 it contained information on more than 1600 experiments from 600 publications. It will be extended and Internet access will also be provided.

Body Burden↗
PubMed2003

Oxygen sensitivity of NMDA receptors: relationship to NR2 subunit composition and hypoxia tolerance of neonatal neurons.

Neonatal rats survive and avoid brain injury during periods of anoxia 25 times longer than adults. We hypothesized that oxygen activates and hypoxia suppresses NMDA receptor (NMDAR) responses in neonatal rat neurons, explaining the innate hypoxia tolerance of these cells. In CA1 neurons isolated from neonatal rat hippocampus (mean postnatal age [P] 5.8 days), hypoxia (PO(2) 10 mm Hg) reduced NMDA receptor-channel open-time percentage and NMDA-induced increase in [Ca(2+)](i) (NMDA DeltaCa(2+)) by 38 and 68% (P<0.01), respectively. In P20 neurons the reductions were not significant. In P3-10 CA1 neurons within intact hippocampal slices, hypoxia reduced NMDA DeltaCa(2+) by 52% (P=0.002) and decreased NMDA-induced death by 45% (P=0.004). Phalloidin, a microtubule stabilizer, prevented hypoxia-induced inhibition of NMDA DeltaCa(2+) in P3-10 neurons. To test whether NMDARs prevalent in neonates (NR1 plus NR2B or NR2D subunits) are inhibited by hypoxia compared with those in mature neurons (NR2A and NR2C), we expressed these receptors in Xenopus oocytes. Compared with responses in 21% O(2), hypoxia (PO(2) 17 mm Hg) reduced currents from neonatal type NR1/NR2D receptors by 25%, increased currents from NR1/NR2C by 18%, and had no effect on NR1/NR2A or NR1/NR2B. Modulation of NMDARs by hypoxia may play an important role in the hypoxia tolerance of the mammalian neonate. In addition, oxygen sensing by NMDARs could play a significant role in postnatal brain development.

Aging↗
PubMed2003

Inactivation of TSE agents: safety of blood and blood-derived products.

Evidence relating to whether the blood of individuals with sporadic Creutzfeldt-Jakob disease is infectious is discussed. The conclusion is that this is unproven. Similar consideration is given to the blood of individuals with variant Creutzfeldt-Jakob disease; it is concluded that there is no convincing evidence that the blood is infectious but reasons for caution are presented. There is discussion regarding factors that add to the safety of plasma-derived therapeutic products, including the capacity of the manufacturing processes to inactivate or remove infectivity by the chemical and physical processes involved. There is extended discussion regarding the inactivation of these types of agents and the few reliable options available in worst-case scenarios such as the processing of instruments used neurosurgically on known or suspected cases. The most effective method is exposure to 1 M sodium hydroxide during autoclaving at 121 degrees C. The inappropriateness of applying any of the most effective methods to blood and blood-products because they are harsh and denaturing is discussed. Nevertheless, such procedures have potential application to the plant used in the manufacture of plasma-products. Evidence is presented which suggests that even more modest treatments (the use of lower concentrations of sodium hydroxide at lower temperatures) are effective when applied to surfaces that are free from any tissue contamination, as is the case with plant used to manufacture plasma-derived products. This evidence has come from studies carried out by the gelatin manufacturers of Europe regarding the capability of their manufacturing systems to inactivate the causal agent of bovine spongiform encephalopathy.

Animals↗
PubMed2003

Antipsychotics and QT prolongation.

OBJECTIVE: To evaluate literature relating to cardiac QT prolongation and the use of antipsychotic drugs. METHOD: Literature searches of EMBASE, Medline, PsychLIT were performed in December 2001 and reference sections of retrieved papers scrutinized for further relevant reports. RESULTS: The Cardiac QTc interval is difficult to measure precisely or accurately but appears to be a useful predictor of risk of dysrhythmia (specifically torsade de pointes) and sudden death. It is less clear that drug-induced QTc prolongation gives rise to similar risks but data are emerging, linking antipsychotic use to increased cardiac mortality. Many antipsychotics have been clearly associated with QTc prolongation. Methodological considerations arguably preclude assuming that any antipsychotic is free of the risk of QTc prolongation and dysrhythmia. CONCLUSION: Available data do not allow assessment of relative or absolute risk of dysrhythmia or sudden death engendered by antipsychotics but caution is advised. Risk of dysrhythmia can very probably be reduced by careful prescribing of antipsychotics in low doses in simple drug regimens which avoid metabolic interactions. Electrocardiographic monitoring may also help to reduce risk but review by specialist cardiologist may be necessary.

Antipsychotic Agents↗
PubMed2003

A generic biokinetic model for predicting the behaviour of the lanthanide elements in the human body.

Information on the biokinetics of the 15 elements of the lanthanide series, 57La to 71Lu, is too sparse to permit individual development of meaningful biokinetic models to describe the behaviour of each of the elements in humans. The lanthanides show a regular gradation in chemical properties across the series, and animal studies indicate that this is reflected in regular differences in their deposition in tissues such as the liver and skeleton. These regular differences in chemical and biological behaviour have been utilised to construct a generic lanthanide biokinetic model and to define element-specific parameters for each element in the series. This report describes the use of the available biokinetic data for humans and animals to derive the parameters for each of the elements.

Animals↗
PubMed2003

A biokinetic model for predicting the retention of 3H in the human body after intakes of tritiated water.

Scarce published data on the long-term excretion of tritiated water from the human body have been re-evaluated in order to develop a biokinetic model describing the retention in the human body of 3H from tritiated water (HTO) that could be used for both prospective and retrospective radiation protection. A three-component exponential function is proposed to describe the elimination of 3H from HTO with biological half-times of 10 d (99.00%), 40 d (0.98%) and 350 d (0.02%) respectively. The model predicts a committed effective dose of 1.7 x 10(-11) Sv Bq(-1), comparable with that of the current ICRP Publication 56 and 72 models, and estimates the retention of 3H to within a factor of about 2 of the measured values up to 40 d after intake and about 5 at times longer than 100 d. The derivation of the model and the uncertainties associated with the various parameters are discussed.

Absorption↗
PubMed2003

A generic model for 11C labelled radiopharmaceuticals for imaging receptors in the human brain.

A large number of radiopharmaceuticals labelled with 11C (half-time 0.340 h) are being developed for positron emission tomographic studies of different types of receptor in the human brain. For most of these agents, the available biokinetic data are insufficient to construct realistic compound-specific biokinetic models for calculating the internal radiation dose delivered to persons undergoing investigation. A generic model for brain receptor substances that predicts the internal dose with sufficient accuracy for general radiation protection purposes has, therefore, been developed. Biokinetic data for 13 11C-radiopharmaceuticals used clinically for imaging different brain receptors indicate that, despite differences in chemical structure, their uptake and retention in the human brain and other tissues are broadly similar. The proposed model assumes instantaneous deposition of 5% of the injected radioactivity in the brain, with the remaining radioactivity being rapidly and uniformly distributed throughout all other tissues. Elimination from all tissues is assumed to occur with a half-time of 2 h. It is further assumed that 75% of the injected 11C is excreted in the urine, and 25% via the gall bladder, with a half-time of 2 h. This model yields an effective dose of 4.5 x 10(-3) mSv MBq(-1), with doses of 3.2 x 10(-2), 1.7 x 10(-2), 8.7 x 10(-3), 5.2 x 10(-3), and 3.8 x 10(-3) mGy MBq(-1) to the urinary bladder, gall bladder, kidneys, brain and ovaries, respectively. These doses are well within the range of those reported using compound-specific models for the radiopharmaceutals studied.

Brain↗
PubMed2003

RBDATA-EULEP: providing information to improve internal dosimetry.

The overall aim of the concerted action RBDATA-EULEP is to provide information to improve the assessments of intakes of radionuclides and of the resulting doses. This involves a review of the behaviour of radionuclides following intake, and the transfer of expertise on methodology by organising small training workshops. The main activity is the development of an electronic database, effectively an annotated bibliography, but the electronic format used facilitates extension, updating and information retrieval. It consists of linked tables of references and experiments, with details and comments on the materials, procedures and results. By June 2002 it contained information on 524 inhalation, 282 ingestion and 164 injection experiments from 391 references. It will be extended, and Internet access provided. Prospective users include groups developing standards for internal dosimetry, scientists conducting research on radionuclide biokinetics and health physicists assessing the consequences of accidental intakes.

Body Burden↗
PubMed2003

Biokinetics of radionuclides and treatment of accidental intakes.

This paper describes the objectives and reviews the progress of EULEP Working Party 5, convened under the auspices of the European Union's Fifth Framework Programme, to 'cluster' two EU-supported contracts, Biokinetics and Dosimetry of Internal Contamination (BIODOS (EU Contract FIS5-1999-00214)) and Radionuclide Biokinetics Database (EULEP) (RBDATA-EULEP (Concerted Action Contract FIS5-1999-00218), and two non-EU funded projects, Biokinetics of Radionuclides in Human Volunteers (RNHV (non-EU funded project)) and Treatment of Accidental Intakes of Radionuclides (TAIR (part funded by EULEP)).

Chelating Agents↗
PubMed2003

Training in cortical control of neuroprosthetic devices improves signal extraction from small neuronal ensembles.

We have recently developed a closed-loop environment in which we can test the ability of primates to control the motion of a virtual device using ensembles of simultaneously recorded neurons /29/. Here we use a maximum likelihood method to assess the information about task performance contained in the neuronal ensemble. We trained two animals to control the motion of a computer cursor in three dimensions. Initially the animals controlled cursor motion using arm movements, but eventually they learned to drive the cursor directly from cortical activity. Using a population vector (PV) based upon the relation between cortical activity and arm motion, the animals were able to control the cursor directly from the brain in a closed-loop environment, but with difficulty. We added a supervised learning method that modified the parameters of the PV according to task performance (adaptive PV), and found that animals were able to exert much finer control over the cursor motion from brain signals. Here we describe a maximum likelihood method (ML) to assess the information about target contained in neuronal ensemble activity. Using this method, we compared the information about target contained in the ensemble during arm control, during brain control early in the adaptive PV, and during brain control after the adaptive PV had settled and the animal could drive the cursor reliably and with fine gradations. During the arm-control task, the ML was able to determine the target of the movement in as few as 10% of the trials, and as many as 75% of the trials, with an average of 65%. This average dropped when the animals used a population vector to control motion of the cursor. On average we could determine the target in around 35% of the trials. This low percentage was also reflected in poor control of the cursor, so that the animal was unable to reach the target in a large percentage of trials. Supervised adjustment of the population vector parameters produced new weighting coefficients and directional tuning parameters for many neurons. This produced a much better performance of the brain-controlled cursor motion. It was also reflected in the maximum likelihood measure of cell activity, producing the correct target based only on neuronal activity in over 80% of the trials on average. The changes in maximum likelihood estimates of target location based on ensemble firing show that an animal's ability to regulate the motion of a cortically controlled device is not crucially dependent on the experimenter's ability to estimate intention from neuronal activity.

Action Potentials↗