Suspected adverse reactions, 2003.
Explore the source record for details and available documents.
Adverse Drug Reaction Reporting Systems↗
Biomedical subjects
C Evans
Publications and source records attributed to C Evans.
Action of kappa and Delta opioid agonists on premotor cardiac vagal neurons in the nucleus ambiguus.
Both enkephalin and dynorphin containing fibers are in close proximity to neurons in the nucleus ambiguus, including cardiac vagal neurons. Microinjection of Delta and kappa agonists into the nucleus ambiguus have been shown to evoke decreases in heart rate. Yet little is known about the mechanisms by which Delta and kappa opioid receptors alter the activity of cardiac vagal neurons. This study tests whether kappa and Delta opioid agonists can alter the activity of cardiac vagal neurons by modulating likely opioid targets including voltage gated calcium currents, and both glycinergic and GABA) neurotransmission to cardiac vagal neurons. Cardiac vagal neurons were identified in vitro by a fluorescent tracer and studied using patch clamp techniques. Neither the kappa agonist spiradoline or the Delta agonist [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) modulated the voltage gated calcium currents in cardiac vagal neurons. DPDPE also did not alter either glycinergic or GABAergic synaptic neurotransmission. Spiradoline did not change GABAergic synaptic inputs, but did significantly inhibit glycinergic synaptic inputs to cardiac vagal neurons. At a concentration of 1 microM, spiradoline inhibited the amplitude of glycinergic events, and at a concentration of 5 microM, spiradoline inhibited both glycinergic amplitude and frequency. Spiradoline also inhibited both the amplitude and frequency of glycinergic miniature inhibitory post-synaptic currents, indicating kappa agonists likely act at both presynaptic and postsynaptic sites to inhibit glycinergic neurotransmission to cardiac vagal neurons.
Analgesics, Opioid↗
Imaging in prostate cancer--a reply.
Explore the source record for details and available documents.
Anesthetics, Local↗
Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans.
The major inflammatory cytokines interleukin(IL)1beta, IL6 and tumor necrosis factor alpha (TNFalpha) play a crucial role in infection, inflammation and stress responses. Previously, three coding genes were resequenced, identifying promoter polymorphisms that were used in association studies of neurodegenerative diseases, metabolic disorders and cancer. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: IL1B-511 C>T, IL6-174 G>C and TNF-308 G>A provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for IL1B, IL6 and TNF/LTA that included the known functional marker but also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 26 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations, a single block with little evidence of historical recombination was observed in IL1B, IL6 and TNF/LTA. For each gene, haplotypes captured the information content of each functional locus, even if that locus was not genotyped, and presumably haplotypes would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using gene haplotype maps and marker panels as tools for linkage studies on related phenotypes.
Black or African American↗
The emerging role of the emergency care practitioner.
OBJECTIVES: To examine the emerging role of the emergency care practitioner (ECP) with comparisons to paramedic practice. Key activities were identified of newly appointed ECPs using qualitative methodology and a qualitative and quantitative comparison of patient treatment was made. METHOD: A constructivist methodology taking account of stakeholder input and drawing upon the constant comparisons of different group's construction of reality. Four practitioners completed reflective patient case studies and adapted patient report forms, which were compared with a second case group of 11 paramedics. In addition individual and focus groups interviews were performed with key stakeholders. RESULTS: In the comparison between ECP and paramedic roles, 331 paramedic incidents were compared with 170 ECP reports. ECPs treated 28% of patients on scene compared with 18% by paramedics (p = 0.007). Fifty per cent of ECPs patients were conveyed compared with 64% of paramedics (p = 0.000). Analysis of the 269 reflective reports and 14 stakeholder interviews revealed four key themes. Firstly, ECPs had a beneficial impact on the deployment of resources, especially relating to non-conveyance. Secondly, their training and education improved their decision making repertoire and developed their confidence for a leadership role. Thirdly, inter-agency collaboration and cooperation was improved, and finally, care benefits were increased especially relating to immediacy of treatment and referral mechanisms. CONCLUSIONS: The results indicate that an investment in the ECP role could be beneficial, however, more work is required to evaluate the development of practice, the quality of care, and cost benefits.
Adolescent↗
The investigation of short stature: a survey of practice in Wales and suggested practical guidelines.
AIM: To survey the investigation of short stature in Wales and suggest guidelines to improve practice. METHODS: Questionnaires were circulated to paediatricians and consultant clinical biochemists or consultant chemical pathologists at 13 Welsh hospitals where children with short stature are investigated. RESULTS: A 100% response was obtained from laboratory and clinical staff. Clinicians screened 1-50 patients each year (median, 10). Growth hormone (GH) deficiency was subsequently diagnosed in 0-30% (median, 10%) and GH treatment started in 30-100% (median, 100%) of patients. Five paediatricians and eight laboratories had written investigative protocols. Investigation of GH secretion was initiated in some centres before a complete clinical evaluation was carried out. Various screening tests for GH deficiency, including insulin-like growth factor 1 (IGF-1), random GH, and exercise tests were used. The clonidine stimulation test was used to assess the GH axis in most centres but eight different protocols were described. GH was measured in four Welsh laboratories using two automated immunoassay methods. However, nine different ranges of cutoff values for defining abnormal GH responses were quoted, and in three centres laboratories and paediatricians quoted different cutoffs. CONCLUSION: This survey demonstrates the need for practical guidelines for the investigation and management of short stature in children, agreed by paediatricians and their laboratory colleagues. The guidelines should encompass the initial clinical investigation, assessment of the GH-IGF-1 axis (using standardised protocols), and provision for the transition to adult management. This article presents practical guidelines based on published points for good practice.
Child↗
Potent thyrotrophin receptor-blocking antibodies: a cause of transient congenital hypothyroidism and delayed thyroid development.
OBJECTIVE: We describe an infant with surprisingly severe neonatal hypothyroidism due to transplacental passage of thyrotrophin receptor (TSH-R)-blocking antibodies (TBAb). DESIGN AND METHODS: TBAb were detected using a cell line which stably expresses the human TSH-R and a cAMP-responsive luciferase reporter by their ability to inhibit TSH-stimulated luciferase expression. Potent TBAb were detected in maternal serum and initially in the infant's serum but, in the latter, TBAb decreased over time to within the reference range by 3-4 months of age, illustrating the transient nature of this condition. RESULTS: The thyroid function of this child did not return to normal on withdrawal of thyroxine therapy at 16 months of age when he developed transient compensated hypothyroidism. CONCLUSIONS: We propose that the presence of potent TBAb in utero and in the first weeks of life may have implications for the development of a normally sized thyroid gland. We have demonstrated the presence of TBAb in the mother's milk and, as far as we are aware, this is the first such report. However, the TBAb in the milk probably did not contribute significantly to hypothyroidism in the child, given the reducing antibody titre in his circulation.
Autoantibodies↗
Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies.
Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers (P trend.0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers.
Adult↗
Mu-opioid receptors are located postsynaptically and endomorphin-1 inhibits voltage-gated calcium currents in premotor cardiac parasympathetic neurons in the rat nucleus ambiguus.
Activation of opioid receptors in the CNS evokes a dramatic decrease in heart rate which is mediated by increases in inhibitory parasympathetic activity to the heart. Injection of opiates into the nucleus ambiguus, where premotor cardiac parasympathetic nucleus ambiguus neurons are located elicits an increase in parasympathetic cardiac activity and bradycardia. However, the mechanisms responsible for altering the activity of premotor cardiac parasympathetic nucleus ambiguus neurons is unknown. This study examined at the electron microscopic level whether premotor cardiac parasympathetic nucleus ambiguus neurons possess postsynaptic opioid receptors and whether mu-opioid receptor agonists alter voltage-gated calcium currents in these neurons. Premotor cardiac parasympathetic nucleus ambiguus neurons were identified in the rat using retrograde fluorescent tracers. One series of experiments utilized dual-labeling immunocytochemical methods combined with electron microscopic analysis to determine if premotor cardiac parasympathetic nucleus ambiguus neurons contain mu-opioid receptors. In a second series of experiments whole cell patch clamp methodologies were used to determine whether activation of postsynaptic opioid receptors altered voltage-gated calcium currents in premotor cardiac parasympathetic nucleus ambiguus neurons in brainstem slices. The perikarya and 78% of the dendrites of premotor cardiac parasympathetic nucleus ambiguus neurons contain mu-opioid receptors. Voltage-gated calcium currents in premotor cardiac parasympathetic nucleus ambiguus neurons were comprised nearly entirely of omega-agatoxin-sensitive P/Q-type voltage-gated calcium currents. Activation of mu-opioid receptors inhibited these voltage-gated calcium currents and this inhibition was blocked by pretreatment with pertusis toxin. The mu-opioid receptor agonist endomorphin-1, but not the mu-opioid receptor agonist endomorphin-2, inhibited the calcium currents. In summary, mu-opioid receptors are located postsynaptically on premotor cardiac parasympathetic nucleus ambiguus neurons. The mu-opioid receptor agonist endomorphin1 inhibited the omega-agatoxin-sensitive P/Q-type voltage-gated calcium currents in premotor cardiac vagal nucleus ambiguus neurons. This inhibition is mediated via a G-protein mediated pathway which was blocked by pretreatment with pertusis toxin. It is possible that the inhibition of calcium currents may act to indirectly facilitate the activity of premotor cardiac parasympathetic nucleus ambiguus neurons by disinhibition, such as by a reduction in inhibitory calcium activated potassium currents.
Analgesics, Opioid↗
Resuscitation Predictor Scoring Scale for inhospital cardiac arrests.
OBJECTIVES: The purpose of this study was to determine the key factors influencing survival from cardiopulmonary resuscitation attempts and to produce a survival predictor scale for use during a resuscitation attempt. METHOD: Bivariate analysis of individual survival predictors and a prospective analysis of survival based on logistic regression models. Included in this seven year study (1993-2000) were 2567 inhospital resuscitation calls of which 1633 received full cardiopulmonary resuscitation. Immediate, 24 hour and discharge survival rates were the main outcome measures with additional analysis for the development of the Resuscitation Predictor Scoring Scale (RPS Scale). RESULTS: The immediate survival rate was 41%, 28% at 24 hours, and 19% by discharge. Multivariate analysis showed the main factors influencing 24 hour survival to be the duration of the arrest, primary arrhythmia (VT, VF, asystole, or PEA), age, and the primary mode of arrest (respiratory or cardiac). The RPS Scale was developed from these key predictors giving resuscitation teams an accurate prediction of survival 15 minutes into a resuscitation attempt. CONCLUSION: Data collection and analysis of cardiopulmonary resuscitation attempts are essential for the formulation of survival indicators. In this case the data have enabled the formulation of a survival predictor scale that will quantify the decision making process regarding the termination of cardiopulmonary resuscitation attempts.
Adult↗
Learning to karyotype in the university environment: a computer-based virtual laboratory class (KaryoLab) designed to rationalize time for the tutor/researcher and to encourage more students to engage in cytogenetics.
The ability to karyotype G-banded chromosome preparations is an essential skill for chromosome biologists. For this reason, the teaching of the rudiments of G banding analysis forms an integral part of the curriculum in many biology and genetics degree courses. The way in which karyotyping is usually taught involves providing the students with a photograph of G-banded chromosomes, a pair of scissors and some glue from which they can cut out the chromosomes and build the karyotype. This has the disadvantage that large amounts of time are taken in cutting and pasting and comparatively little in learning pattern recognition of individual chromosomes. In this paper we describe the development of a computer-based student practical class "KaryoLab". To the best of our knowledge, this is the first report of a teaching tool that combines instruction in cytogenetic analysis with both formative and summative feedback to the student and a virtual elimination of marking time for the tutor. Chromosome research and diagnostics will only continue while there are sufficiently motivated and trained individuals to perform it. We see the software developed here as a significant step towards training and motivating students in cytogenetics.
Computer-Assisted Instruction↗
Objectivity in psychoanalytic assessment of couple relationships.
BACKGROUND: Clinicians claim that partners in a couple can be understood to share a mode of relating, at an unconscious level. Assessment of this depends on inference from observable data. This study tests the viability and reliability of a modification of the Personal Relatedness Profile (PRP) for this purpose. AIMS: To test the interrater reliability and construct validity of a joint PRP score for couples. METHOD: Seven therapists independently rated couples' interactions using the 30-item PRP and segments of videotaped interviews with 19 couples. RESULTS: Interrater reliability was good and correlations between items clearly supported the underlying Kleinian bipolar model used (paranoid-schizoid/ depressive positions). CONCLUSIONS: Psychoanalytic couple psychotherapists agree in independent judgements of the nature of couple functioning, these judgements being based on envisaging couples in terms of an unconsciously shared state of mind.
Couples Therapy↗
The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population.
Congenital hypothyroidism (CH) occurs in approximately 1 in 3000 births and can be caused by mutations in 9 known genes, including that encoding the TSH receptor (TSHR). We report on two Welsh siblings, detected by neonatal screening, who had normal sized and placed glands but negative isotope uptake. Genomic DNA was obtained from both siblings and parents, the TSHR amplified using pairs of intronic and/or overlapping exonic primers and the PCR products sequenced automatically. Both siblings were homozygous for a previously described G to A transition producing a missense mutation, W546X, in the fourth membrane spanning region of the TSHR, rendering it unresponsive to TSH. Both parents were heterozygous and unrelated; furthermore, the W546X has been described in three further families (one of which is Welsh), suggesting that it may be a relatively common mutation. We genotyped 368 euthyroid Welsh individuals using single nucleotide primer extension, and found 366 homozygous wild-type (G:G) and 2 heterozygous (G:A) for the mutation. In conclusion, CH in the siblings is due to the missense mutation, W546X, in their TSHR gene. The W546X allele was detected in approximately 1 in 180 individuals and may be a major contributor to hypothyroidism in the Welsh population.
Alleles↗
Thyroglobulin: current aspects of its role in autoimmune thyroid disease and thyroid cancer.
Thyroglobulin (Tg) is a large glycoprotein (molecular weight: 660000) with 2 polypeptide chains of approximately 2768 amino acids each. It functions both as a pro-hormone and storage hormone for thyroid hormones. The complete Tg gene sequence has been determined for human, rat and bovine species. Tg is one of the thyroid autoantigens recognised in patients with autoimmune thyroid disease (AITD). Antibodies to Tg (TgAb) are present in the serum of patients with AITD and are also sometimes present in healthy euthyroid subjects. Though at least 40 antigenic epitopes on human Tg have been identified, only 2 or 3 of these bind TgAb. Epitope mapping studies suggest that TgAb in AITD patients express a restricted binding pattern while TgAb in the serum of healthy individuals do not show such specific binding. There is evidence to suggest that iodination of Tg may alter these epitope binding patterns. TgAb IgG on the other hand, do not appear to be subclass restricted. Several Tg fragments capable of inducing a T-cell response have been described. Tg is routinely used in the postoperative monitoring of patients with differentiated thyroid cancer. Its use has been limited by problems with assay methods which include poor inter-laboratory standardisation, poor inter-assay variation, low functional sensitivity of the assays, hook effects, and interference from TgAb present in patients serum. The use of rh-TSH in stimulating Tg prior to testing has improved the sensitivity of Tg values in the suppressed state.
Autoantibodies↗
Evaluation of a commercial line probe assay for identification of mycobacterium species from liquid and solid culture.
The performance of a commercial line probe assay (LiPA) (Inno-LiPA Mycobacteria; Innogenetics, Belgium) for the detection and identification of Mycobacterium species from liquid and solid culture was evaluated at five routine clinical laboratories. The LiPA method is based on the reverse hybridization principle, in which the mycobacterial 16S-23S ribosomal RNA (rRNA) spacer region is amplified by polymerase chain reaction (PCR). Amplicons are subsequently hybridized with oligonucleotide probes arranged on a membrane strip and detected by a colorimetric system. The test detects the presence of Mycobacterium species and specifically identifies Mycobacterium tuberculosis complex, Mycobacterium kansasii, Mycobacterium xenopi, Mycobacterium gordonae, Mycobacterium avium complex, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium scrofulaceum, and Mycobacterium chelonae - Mycobacterium abscessus complex. The results of LiPA were compared with the results obtained using traditional biochemical and molecular tests (DNA probe-based techniques, PCR restriction enzyme analysis of the 65 kDa heat-shock protein gene, and sequencing of the 16S rDNA). A total of 669 isolates, 642 of which were identified as Mycobacterium species and 27 as non- Mycobacterium species, were tested by LiPA. After analysis of 14 initially discordant results and exclusion of one isolate, concordant results were obtained for 636 of 641 Mycobacterium isolates (99.2% accuracy). All Mycobacterium species reacted with the MYC ( Mycobacterium species) probe (100% sensitivity), and all non- Mycobacterium species were identified as such (100% specificity).
Bacterial Typing Techniques↗
Regulating dental nursing in the UK.
There has been much discussion about the impending legislation for compulsory registration of dental nurses. A questionnaire survey of Oxfordshire dental practices found that 60% (153/254) of dental nurses had no formal qualifications. Of these 49% (75/153) were already on a training course or planning to apply for one although those who achieve mediated entry may discontinue training. Overall, 40% (62/153) were planning to apply for mediated entry. Previous research indicates that there may be similarly high proportions of unqualified dental nurses throughout the UK. There are concerns that a rigid training programme and compulsory examinations will compound existing recruitment problems, and create a national shortfall of dental nurses. Proponents believe that formal training will better equip dental nurses to handle the demands of modern dental practice and bring them in line with other auxiliary health personnel. Training needs to be co-ordinated nationally to ensure adequate access and consistent standards. Dental nurses and practices should be consulted and supported throughout the implementation period.
Dental Assistants↗
Arginine vasopressin enhances GABAergic inhibition of cardiac parasympathetic neurons in the nucleus ambiguus.
Previous studies have shown that arginine vasopressin is an important neuropeptide that can modulate the reflex control of blood pressure and heart rate. The nucleus ambiguus, where cardiac parasympathetic neurons are located, receives dense arginine vasopressin projections. However the mechanisms by which arginine vasopressin alters cardiac parasympathetic activity are unknown. We tested the hypothesis that arginine vasopressin can alter the activity of cardiac parasympathetic neurons by altering the spontaneous GABAergic input to these neurons. Experiments were conducted using whole cell patch clamp recordings of cardiac parasympathetic neurons in an in vitro slice preparation in rats. The results of this study demonstrate that arginine vasopressin increases the frequency and amplitude of GABAergic inhibitory post-synaptic currents in cardiac parasympathetic neurons. Arginine vasopressin did not alter the GABAergic currents evoked by exogenous application of GABA. Similarly, in the presence of tetrodotoxin, arginine vasopressin did not alter the frequency, amplitude or decay time of GABAergic miniature synaptic events evoked by high osmolarity. These results indicate that arginine vasopressin likely acts on neurons precedent to cardiac parasympathetic neurons and that arginine vasopressin likely acts not at the synaptic terminal but at the soma or dendrites of the precedent neuron. Oxytocin and agonists for the V(2)-arginine vasopressin and V(1b)-arginine vasopressin receptors had no effect. By contrast, the arginine vasopressin-evoked responses were completely abolished by a selective V(1a)-arginine vasopressin receptor antagonist indicating arginine vasopressin responses are mediated by V(1a)-arginine vasopressin receptors. We conclude that the V(1a)-arginine vasopressin receptor-mediated increase in frequency and amplitude of inhibitory GABAergic activity to cardiac parasympathetic neurons may be at least one mechanism by which central arginine vasopressin may increase heart rate and inhibit reflex bradycardia.
Animals↗
Endomorphin-2 inhibits GABAergic inputs to cardiac parasympathetic neurons in the nucleus ambiguus.
The nucleus ambiguus is an area containing cardiac vagal neurons, from which originates most of the parasympathetic control regulating heart rate and cardiac function. GABAergic pathways to these neurons have recently been described, yet modulation of this GABAergic input and its impact upon cardiac vagal neurons is unknown. The nucleus ambiguus has been shown to contain mu-opioid receptors and endomorphin-1 and endomorphin-2, the endogenous peptide ligands for the mu-receptor, whilst microinjections of opioids in the ambiguus area evoke bradycardia. The present study therefore examined the effects of endomorphin-1, endomorphin-2 and DAMGO (a synthetic, mu-selective agonist) on spontaneous GABAergic IPSCs in cardiac parasympathetic neurons. Only endomorphin-2 (100 microM) produced a significant inhibition, of both the frequency (-22.8%) and the amplitude (-30.5%) of the spontaneous IPSCs in cardiac vagal neurons. The inhibitory effects of endomorphin-2 were blocked by naloxonazine (10 microM), a selective mu(1) receptor antagonist. Naloxonazine alone (10 microM) had a potentiating effect on the frequency of the GABAergic IPSCs (+161.43%) but not on the amplitude, indicating that GABA release to cardiac vagal neurons may be under tonic control of opioids acting at the mu(1) receptor. Endomorphin-2 did not reduce the responses evoked by exogenous application of GABA. These results indicate that endomorphin-2 acts on mu(1) receptors located on precedent neurons to decrease GABAergic input to cardiac vagal neurons located in the nucleus ambiguus. The subsequent increase in parasympathetic outflow to the heart may be one mechanism by which mu-selective opioids act to induce bradycardia.
Action Potentials↗