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Biomedical subjects

R Watkins

Publications and source records attributed to R Watkins.

At least 19 recordsLinked to original sources
PubMed2006

'Coming out' with Alzheimer's disease: changes in awareness during a psychotherapy group for people with dementia.

This paper forms part of the second phase of a project looking at those changes that occurred for participants during a series of time-limited psychotherapy groups for people with dementia. Using the Assimilation of Problematic Experiences Scale (APES), the accounts of one participant (Robert) are analyzed across the course of the group. Robert moves from a position in which he wards off awareness that he has dementia of the Alzheimer's type, to being able to joke about having brain changes that are symptomatic of the illness. This change in his discourse about Alzheimer's disease was accompanied by an increase in Robert's levels of affect. However, reflecting on the changes that had occurred for him, Robert commented that before he came to the group he had been frightened, thinking that 'I'm going crazy?...?what am I going to be like in another five years?'. For Robert, coming to the group had meant that this fear had been replaced by the knowledge that he was not alone. In the light of the move towards early diagnosis, the importance of this model of change in awareness as a means of increasing understanding of the process of emotional development is discussed.'...?but I think that a lot of people who I have met who have come out about Alzheimer's were quite shocked because I said that. It did help, it may not have helped others, but I suppose that it helps overcome a feeling of being different.'Janet, session six.

Aged↗
PubMed2004

Mapping of the prostate in endorectal coil-based MRI/MRSI and CT: a deformable registration and validation study.

The endorectal coil is being increasingly used in magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) to obtain anatomic and metabolic images of the prostate with high signal-to-noise ratio (SNR). In practice, however, the use of endorectal probe inevitably distorts the prostate and other soft tissue organs, making the analysis and the use of the acquired image data in treatment planning difficult. The purpose of this work is to develop a deformable image registration algorithm to map the MRI/MRSI information obtained using an endorectal probe onto CT images and to verify the accuracy of the registration by phantom and patient studies. A mapping procedure involved using a thin plate spline (TPS) transformation was implemented to establish voxel-to-voxel correspondence between a reference image and a floating image with deformation. An elastic phantom with a number of implanted fiducial markers was designed for the validation of the quality of the registration. Radiographic images of the phantom were obtained before and after a series of intentionally introduced distortions. After mapping the distorted phantom to the original one, the displacements of the implanted markers were measured with respect to their ideal positions and the mean error was calculated. In patient studies, CT images of three prostate patients were acquired, followed by 3 Tesla (3 T) MR images with a rigid endorectal coil. Registration quality was estimated by the centroid position displacement and image coincidence index (CI). Phantom and patient studies show that TPS-based registration has achieved significantly higher accuracy than the previously reported method based on a rigid-body transformation and scaling. The technique should be useful to map the MR spectroscopic dataset acquired with ER probe onto the treatment planning CT dataset to guide radiotherapy planning.

Algorithms↗
PubMed2001

MMR vaccine in HIV-infected children -- potential hazards?

Although given routinely as prophylaxis against wild-type measles to HIV-infected children, the live attenuated measles component of the MMR triple vaccine also possesses potential for disease. We document a case of measles proven to be caused by vaccine strain in a HIV-infected child here in the UK and discuss the clinical and immunological aspects. We also consider the new guidelines for MMR vaccination in HIV-infected children adopted last year in the USA.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Muscarinic agonists and antagonists in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment and personality changes. The development of drugs for the treatment of the cognitive deficits of AD has focused on agents which counteract loss in cholinergic activity. Although symptoms of AD have been successfully treated with acetylcholinesterase inhibitors (tacrine, donepezil. rivastigmine, galanthamine), limited success has been achieved with direct M1 agonists, probably due to their lack of selectivity versus other muscarinic receptor subtypes. Muscarinic M2 antagonists have been reported to increase synaptic levels of acetylcholine after oral administration to rats (e.g. BIBN-99, SCH-57790), but their selectivity versus other muscarinic receptor subtypes is modest. Exploration of a series of piperidinylpiperidines has yielded the potent and selective M2 antagonist SCH-217443. This antagonist has excellent bioavailability in rats and dogs and shows activity in a rat model of cognition.

Alzheimer Disease↗
PubMed2001

Antioxidant properties of evening primrose seed extracts.

The antioxidant activity of extracts of evening primrose seeds (SE) and a commercially extracted filter cake (FC) were determined. The SE and FC were extracted with methanol/water (9:1) followed by evaporation and concentration. Extracts were tested in a bulk oil system and an oil-in-water emulsion using safflower oil as the major source of lipids. The antioxidant activity of the extracts was compared to that of a control and to that of butylated hydroxytoluene (BHT), singly, and in combination. Antioxidant activity was measured by the co-oxidation of beta-carotene, an oxidative stability instrument, conjugated dienes, and headspace analysis of hexanal. The SE extract had greater antioxidant activity than the FC extract. The SE extract was more effective in controlling the oxidation in the oil-in-water model system than in the bulk oil system. The activity of SE was concentration dependent, and at higher concentrations the SE was as effective as BHT, but it required higher concentrations because of its lack of purity. Synergism between SE and BHT was demonstrated in both model systems.

Antioxidants↗
PubMed2001

Epstein-Barr virus infectious mononucleosis.

The Epstein-Barr virus (EBV) is the aetiological agent of classical infectious mononucleosis. This review article describes the antigenicity of the virus, the specific antibody response and the stimulated polyclonal heterophile antibody production in the host. The diagnostic tests for EBV infection are discussed, with particular attention drawn to the pitfalls of the Monospot test. Complications are listed and management strategies are outlined. The uses and complications of steroids are discussed. The importance of avoidance of contact sport and the association with splenic rupture is described.

Antibodies, Heterophile↗
PubMed2001

Evaluation of the quality of generic polymethylmethacrylate intraocular lenses marketed in India.

PURPOSE: To determine the quality of single-piece, allpolymethylmethacrylate (PMMA) Intraocular lenses (IOLs) from eght generic manufacturers marketing their product in India. This assessment of quality was made with respect to compliance with internationa standards for the manufacture of IOLs, specifically those parameters most likely to affect patient postoperat ve visual acuity and the long-term biocompatibility of the implanted lens. METHODS: Ten IOLs from each of eight manufacturers were purchased randomly from commercial retail outlets in India. Each IOL, in a masked fashion, had its physical dimensions, optical performance and cosmetic appearance assessed, using the methods prescribed in ISO 11979-2 and 11979-3. Validation of manufacturing process controls were determined by statistical process contro techniques. Four IOLs from each manufacturer were also tested for the presence of unpolymerized PMMA using gas chromatography. RESULTS: Only lenses from two IOL manufacturers complied with the optical and mechanical standards. All other manufacturers' lenses failed one or more of these tests. Intraocular lenses from only two producers met with surface quality and bulk homogeneity standards. All others exhibited defects such as surface contamination and scratches, poor polishing, and chipped or rough positioning holes. Lenses from two producers exhibited high levels of methylmethacrylate monomer (MMA). CONCLUSIONS: Non-clinical grade PMMA starting material may have been used in the manufacture of IOLs by some producers. Critical manufacturing defects occurred in the IOLs from five of the eight producers tested. Only one manufacturer's IOLs met all specifications, and on statistical analysis demonstrated good manufacturing process contro with respect to the properties tested. With the widespread acceptance of IOL implantation in developing countries, such as India, it is essential that in the rush to make this the norm, the quality of implants used not be overlooked.

Biocompatible Materials↗
PubMed2001

Peculiar velocity surveys: optimal moments analysis.

A new formalism to analyze peculiar velocity surveys is presented. Results from these surveys are shown to be dominated by small-scale noise, aliasing, and incomplete cancellations. The formalism allows us to filter out the signal from scales that are not of interest and thus provides us with a clean signal that probe large scales. We use maximum likelihood techniques to analyze the filtered data and compare it to the analysis of the full dataset. The filtered analysis gives a much better parameter estimation than the full analysis, leading us to conclude that, indeed, the large-scale signal is obscured by small-scale noise.

Journal Article↗
PubMed2001

Intraocular pressure and pulsatile ocular blood flow after retrobulbar and peribulbar anaesthesia.

AIMS: This study investigated the effect of peribulbar and retrobulbar local anaesthesia on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF), as such anaesthetic techniques may adversely affect these parameters. METHODS: 20 eyes of 20 patients who were to undergo phacoemulsification cataract surgery were prospectively randomised to receive peribulbar or retrobulbar anaesthesia. The OBF tonometer (OBF Labs, Wiltshire, UK) was used to simultaneously measure IOP and POBF before anaesthesia and 1 minute and 10 minutes after anaesthesia. Between group comparisons of age, baseline IOP, and baseline POBF were performed using the non-parametric Mann-Whitney test. Within group comparisons of IOP and POBF measured preanaesthesia and post-anaesthesia were performed using the non-parametric Wilcoxon signed ranks test for both groups. RESULTS: There was no statistically significant IOP increase post-anaesthesia in either group. In the group receiving peribulbar anaesthesia, there was a significant reduction in POBF initially post-anaesthesia which recovered after 10 minutes. In the group receiving retrobulbar anaesthesia, there was a persistent statistically significant reduction in POBF. CONCLUSIONS: Retrobulbar and peribulbar injections have little effect on IOP. Ocular compression is not needed for IOP reduction when using local anaesthesia for cataract surgery. Conversely, POBF falls, at least for a short time, when anaesthesia for ophthalmic surgery is administered via a retrobulbar route or a peribulbar route. This reduction may be mediated by pharmacologically altered orbital vascular tone. It may be safer to use other anaesthetic techniques in patients with ocular vascular compromise.

Aged↗
PubMed1999

Biosynthesis of inositol trisphosphate receptors: selective association with the molecular chaperone calnexin.

A prominent labelled polypeptide having the same mobility as type-I inositol trisphosphate receptor (IP(3)R) was immunoprecipitated from WB-cell lysates by antibodies to calnexin, an ER integral membrane chaperone. The identity of this polypeptide was confirmed by re-immunoprecipitation of the radioactive polypeptides released from calnexin-antibody immunoprecipitates with type-I IP(3)R antibody. The interaction of calnexin with newly synthesized type-I IP(3)R was transient and inhibited by treatment of the cells with dithiothreitol or the glucosidase inhibitor N-methyldeoxynojirimicin. In similar experiments, there was no evidence for the binding of type-I IP(3)R to calreticulin, an ER luminal chaperone. Calnexin (but not calreticulin) associated with newly synthesized FLAG (DYKDDDDK epitope)-tagged type-III IP(3)R expressed in COS-7 cells. In order to further define the mechanism of interaction of nascent IP(3)R with chaperones, we have utilized an in vitro rabbit reticulocyte translation assay programmed with RNA templates encoding the six putative transmembrane (TM) domains of IP(3)Rs. In accordance with the known preference of calnexin for monoglucosylated oligosaccharide chains, calnexin antibody preferentially immunoprecipitated a proportion of glycosylated type-I translation product. Addition of glucosidase inhibitors prevented the association of calnexin with in vitro translated type-I TM construct. Using truncated RNA templates we found that calnexin did not associate with the first four TM domains but retained affinity for the construct encoding TM domains 5 and 6, which contains the glycosylation sites. We propose that calnexin is a key chaperone involved in the folding, assembly and oligomerization of newly synthesized IP(3) receptors in the ER.

Animals↗
PubMed1999

Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver.

We investigated the possibility that the flavonoid mixture, silymarin (SY), administered as the compound Silymarin Phytosome (PHYTO), could protect the fetus from maternally ingested EtOH. Seventy-six female rats were randomly assigned to one of seven groups: pair-fed control; chow fed control; EtOH; and four groups receiving EtOH and PHYTO in varying dosages. All groups except the chow-fed control were maintained on a liquid diet. On day 1 of pregnancy the dams began the treatment protocol. On day 21 of pregnancy the rats were sacrificed and the fetuses removed. Gamma glutamyl transpeptidase (GGTP) activity was determined for liver and brain tissue from both the fetuses and the dams. GGTP activity in the EtOH/silymarin treatment groups did not differ significantly from that observed for the pair-fed control group. The observed GGTP activity levels for the EtOH-only group were significantly higher than those attained by the pair-fed control group. Although GGTP activity did not vary significantly with the quantity of PHYTO administered, as PHYTO dose was increased, GGTP activity decreased.

Animals↗
PubMed1997

Synthesis and evaluation of polycyclic pyrazolo[3,4-d]pyrimidines as PDE1 and PDE5 cGMP phosphodiesterase inhibitors.

Polycyclic pyrazolo[3,4-d]pyrimidines (represented by 3 and 4) were synthesized as analogues of the recently reported polycyclic guanine phosphodiesterase (PDE) inhibitors. From the structure-activity relationship (SAR) development of a series of compounds, it was discovered that C-3 benzyl and N-2 methyl disubstitution on the pyrazole ring gave the best combination of potency and selectivity for PDE1 and PDE5 cGMP PDEs as represented by compound 4c: PDE1, IC50 = 60 nM; PDE3, IC50 = 55,000 nM; PDE5, IC50 = 75 nM. These compounds were also evaluated in vivo and found to be good orally active antihypertensives in laboratory animal models. Finally, comparisons were made of the in vitro and in vivo profiles of the pyrazolo-[3,4-d]pyrimidine compound 4c with those of two representative guanine compounds.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Determination of a cyclic guanine monophosphate phosphodiesterase inhibitor (SCH 51866) in rat serum using capillary zone electrophoresis.

A capillary zone electrophoretic (CZE) assay was developed for the determination of cis-5,6a,7,8,9,9a-hexahydro-2-[4-(trifluoromethyl)phenylmethyl]-5-methyl - cyclopent[4,5]imidazo[2,1-b]purin-4(3H)-one, SCH 51866 (I), a cyclic guanine monophosphate phosphodiesterase inhibitor, in rat serum using acetonitrile deproteination as a clean-up step before injection. The calibration curve was linear over a serum concentration range of 0.5 to 10 micrograms/ml serum with a correlation coefficient (r) > 0.99. The limit of quantitation (LOQ) was established at 0.5 micrograms/ml. Fifty microliters of serum were used for analysis, which allowed serial bleeding (8 samples) from a single rat to characterize the pharmacokinetic profile of I after either oral or intravenous drug administration. In traditional pharmacokinetic and toxicokinetic studies in rodents, one animal provides only one serum sample since 1 to 2 ml of sample volume is required for chromatographic analysis, resulting in the use of a large number of animals per study. This assay yields a significant reduction in the use of animals, hence providing a large reduction in resources and time in drug discovery and development.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1995

Optimal temporal frequencies in oscillatory movement hyperacuity measurements of visual function in cataract patients.

Hyperacuity tasks have been suggested for the assessment of potential visual function in the presence of cataracts. To test this suggestion, hyperacuity thresholds for an oscillating bar were measured in 30 subjects with idiopathic cataract and in 24 age-matched normals over a range of oscillation frequencies. Each subject's cataract was categorized using the Oxford Clinical Cataract Classification and Grading System. Cataract was found to have a significant effect on thresholds, although a differential morphological effect on thresholds was equivocal. Thresholds at higher temporal frequencies were significantly raised when compared to the normal group. The main conclusion to be drawn from this study is that motion hyperacuity thresholds appear unaffected by cataract at low oscillation frequencies and should be used in preference to higher frequencies in the assessment of such patients.

Aged↗