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Biomedical subjects

K Williams

Publications and source records attributed to K Williams.

At least 181 records · Page 10Linked to original sources
PubMed1998

Survival in cerebral palsy: the role of severity and diagnostic labels.

The aim of this study was to review survival and certified causes of death of 584 children on a population-based register of cerebral palsy (CP), and to assess the impact on these of an additional diagnostic label. The register, established in 1985, comprised children with CP born from 1980 to about 1987 who were resident at the time of notification in the south-east of England in a region with between 3 and 4 million population, defined by the boundaries of the regional health authority (North East Thames Regional Health Authority). The current report concerns deaths of residents born between 1980 and 1986, who had been registered but had later died, as well as of eligible children who had not been registered while alive but whose cause of death was CP. These were identified at the Office of Population Censuses and Surveys who also supplied copies of death certificates for this study. For children notified while alive, information about motor severity and other diagnostic labels was sought at entry to the register and again between 3.5 and 4 years and between 7 and 8 years. For this study, children known to have a postneonatal onset, a progressive or non-cerebral cause of motor signs, or minimal motor involvement were excluded. Thirty-nine of 584 children included in this study had died by the end of 1995. No deaths had occurred in children known to have less than four-limb involvement. Survival of the group known to have an additional diagnostic label was significantly lower (86.2%) than that of the group with no known label (96.3%; P=0.01), and remained lower, although not significantly, if only those with severe four-limb involvement were compared (75.3% versus 92.4%; P=0.2). The greater severity of limb involvement in those with an additional diagnosis may not account for this difference. Of the 37 children with death certificates available, CP was mentioned as a cause in only 24.

Cause of Death↗
PubMed1998

Pharmacokinetics of an antisense oligonucleotide injected intravitreally in monkeys.

The kinetics of an intravitreally administered phosphorothioate oligonucleotide, ISIS 2922, were studied in cynomolgus monkeys. Vitreal and retinal concentrations were measured after administration of 11, 57, or 115 microg/eye. ISIS 2922 concentrations in vitreous and retina were compared, after single, weekly, or biweekly doses, for potential accumulation. ISIS 2922 levels were quantified using solid-phase extraction followed by capillary gel electrophoresis. Concentrations of ISIS 2922 in the vitreous were proportional to the dose and were nearly linear with respect to the dose. The ISIS 2922 concentrations 3 days after dosing ranged from 80 nM to approximately 1.5 microM. By 14 days after intravitreal injection, the concentrations were below the limit of quantitation (<10 nM) for all dose groups. There was no accumulation in the vitreous after multiple weekly or biweekly doses. The concentrations of ISIS 2922 in the retina 2 days after a single intravitreal injection ranged from 50 nM to 1.1 microM. The uptake and disposition of ISIS 2922 in the retina appeared to have been saturated between the 57- and 115-microg doses; the average concentrations were 0.71 +/- 0.24 microM (N = 4) and 0.88 +/- 0.27 microM (N = 3) for the two doses, respectively. Electrophoretic profiles of extracts revealed multiple chain-shortened oligonucleotides in the vitreous and retina, suggesting extensive metabolism in both compartments. Analyses from the multiple-dose study suggested that accumulation was dependent on the total administered dose, with accumulation occurring after biweekly dosing in the 115-microg dose group and only after weekly dosing in the 57-microg dose group.

Animals↗
PubMed1998

Self-assessment of clinical competence by general practitioner trainees before and after a six-month psychiatric placement.

BACKGROUND: General practitioners (GPs) are responsible for managing the majority of mental health problems. There is evidence that the recognition and management of mental disorders could be improved. Vocational training schemes including a placement in psychiatry should be a prime opportunity to develop the requisite skills. AIM: To determine whether GP trainees thought that a six-month psychiatric placement had improved their clinical competence. METHOD: Questionnaires were sent to 18 junior doctors in the south-west region entering a senior house officer placement in psychiatry. Trainees rated their perceived competency in 20 skill areas at the beginning and at the end of six months. Comparisons between matched trainees were made using ranking techniques. RESULTS: There was a statistically significant improvement (P < 0.05) in perceived efficacy for matched trainees in 19 of the 20 areas of clinical competency appraised. The exception was in the confidence to identify different types of eating disorders. On completion of training, ability to diagnose depression, take a psychiatric history, and examine mental state were ranked most highly. However, skill levels in dealing with problems such as prescribing in acute psychosis and managing psychiatric emergencies were generally ranked above those dealing with neurotic and psychological problems. Most trainees indicated a favourable impression of their training experience. CONCLUSIONS: Clinical competency appeared to improve in all but one of the areas appraised. However, skills were ranked more highly in dealing with hospital-based problems than those likely to be encountered in primary care. This may have implications for the focus of psychiatric training currently received.

Adult↗
PubMed1997

Report of the Canadian Hypertension Society Consensus Conference: 1. Definitions, evaluation and classification of hypertensive disorders in pregnancy.

OBJECTIVES: To provide Canadian physicians with a standard definition of hypertension in pregnancy, recommendations for laboratory investigations and tests for the assessment and management of hypertensive disorders in pregnancy, and a classification of such disorders. OPTIONS: To improve or not improve Canadian uniformity and standardization in the investigation and classification of hypertensive disorders in pregnancy. OUTCOMES: 1) Accuracy, reliability and practicality of diagnostic clinical criteria for hypertensive disorders in pregnancy. 2) Laboratory tests useful to determine severity and prognosis of disorders as measured by maternal and neonatal adverse outcomes. 3) A classification of disorders for use by Canadian physicians to facilitate uniformity and diffusion of research through a common language. EVIDENCE: Articles on hypertensive disorders in pregnancy published from 1966 to 1996, retrieved through MEDLINE search, related to definitions, tests, diagnostic criteria and classification, as well as documents on diagnosis and classification from authorities in the United States, Europe and Australia and from special interest groups. VALUES: High priority was given to the principle of preventing adverse maternal and neonatal outcomes through the provision of diagnostic criteria for severity and prognosis and through dissemination of reliable and pertinent information and research results using a common language. BENEFITS, HARMS AND COST: Higher degree of vigilance in diagnosing hypertensive disorders in pregnancy, allowing for earlier assessment and intervention, and more efficient dissemination of comparative information through common language. No harm or added cost is perceived at this time. RECOMMENDATIONS: (1) A diastolic blood pressure of 90 mm Hg or more should be the criterion for a diagnosis of hypertension in pregnancy and should trigger investigation and management. Except for very high diastolic readings (110 mm Hg or more), all diastolic readings of 90 mm Hg or more should be confirmed after 4 hours. (2) A regularly calibrated mercury sphygmomanometer, with an appropriate-sized cuff, is the instrument of choice. A rest period of 10 minutes should be allowed before taking the blood pressure. The woman should be sitting upright and the cuff positioned at the level of the heart. (3) Both Korotkoff phase IV and V sounds should be recorded, but the phase IV sound should be used for initiating clinical investigation and management. (4) A urine protein level of more than 0.3 g/d should be the criterion for a diagnosis of proteinuria; 24-hour urine collection should be the standard method for determining proteinuria. (5) Edema and weight gain should not be used as diagnostic criteria. (6) Hypertensive disorders diagnosed during pregnancy should be classified as pre-existing hypertension; gestational hypertension with or without proteinuria; pre-existing hypertension with superimposed gestational hypertension with proteinuria; and unclassifiable antenatally but final classification 42 days after delivery. VALIDATION: Except for expert opinions and reviews solicited for this project, these recommendations need to be field tested and validated in Canada. Guidelines endorsed by the Canadian Hypertension Society and the Society of Obstetricians and Gynaecologists of Canada.

Blood Pressure Determination↗
PubMed1997

Interactions of polyamines with ion channels.

Endogenous polyamines, in particular spermine, have been found to cause block and modulation of a number of types of ion channel. Intracellular spermine is responsible for intrinsic gating and rectification of strong inward rectifier K+ channels by directly plugging the ion channel pore. These K+ channels control the resting membrane potential in both excitable and non-excitable cells, and control the excitability threshold in neurons and muscle cells. Intracellular spermine causes inward rectification at some subtypes of Ca2+-permeable glutamate receptors in the central nervous system, again by plugging the receptor channel pore, and spermine can even permeate the ion channel of these receptors. Extracellular spermine has multiple effects at the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor, including stimulation that increases the size of NMDA receptor currents, and voltage-dependent block. A number of polyamine-conjugated arthropod toxins and synthetic polyamine analogues are potent antagonists of glutamate receptors, and represent new tools with which to study these receptors. Interactions of polyamines with other types of cation channels have been reported. This area of research represents a new biology and a new pharmacology of polyamines.

Animals↗
PubMed1997

Quantitative analysis of GAP-43 expression by neurons in microcultures using cell-ELISA.

A cell-ELISA technique is described which allows the quantification of GAP-43 protein in a large number of microcultures of adult dorsal root ganglion neurons. GAP-43 is measured in the 1-10 ng range, corresponding to the amount of GAP-43 present in fewer than 500 DRG neurons. Specificity of the assay is confirmed using Western blotting and immunocytochemistry. The GAP-43 content of adult DRG microcultures rises during 2 weeks in culture, although the number of surviving neurons decreases. The GAP-43 content of cultured adult DRG neurons is not increased by chronic exposure to added nerve growth factor after 7 days in vitro. However, GAP-43 is increased in DRG taken from animals with prior peripheral nerve injury, and is decreased by chronic exposure to dibutyryl cyclic AMP after 7 days in vitro. The method affords the sensitivity and statistical power to document modest changes in GAP-43 protein abundance in complex cultures.

Animals↗
PubMed1997

Influence of extracellular pH on inhibition by ifenprodil at N-methyl-D-aspartate receptors in Xenopus oocytes.

Ifenprodil is an atypical N-methyl-D-aspartate (NMDA) receptor antagonist that selectively blocks receptors containing the NR2B subunit. It has been proposed that ifenprodil may act at a stimulatory polyamine site on NMDA receptors, although interactions between ifenprodil and polyamines are non-competitive. NMDA receptors are also inhibited by extracellular protons, and an interaction between protons and polyamine stimulation has been described. Using voltage-clamp recording of recombinant NR1/NR2B receptors expressed in oocytes, ifenprodil inhibition was found to be pH sensitive with a smaller inhibition at alkaline pH. Similar effects of pH were seen on inhibition by nylidrin, eliprodil, and haloperidol, which are thought to act at the ifenprodil binding site. The pH sensitivity of ifenprodil block occurs at NR1B/NR2B as well as NR1A/NR2B receptors, suggesting that it is not influenced by the exon-5 insert that is present in NR1B but absent in NR1A. Protons may directly affect the ifenprodil binding site or may alter the coupling of ifenprodil binding to inhibition of channel gating.

Animals↗
PubMed1997

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Humans↗