On the evidence. Dental restoration.
Explore the source record for details and available documents.
Clinical Competence↗
Biomedical subjects
R Richardson
Publications and source records attributed to R Richardson.
Clinical governance. PA for the course?
Explore the source record for details and available documents.
Evidence-Based Medicine↗
The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation.
The suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and they act as a negative feedback loop by subsequently inhibiting the JAK/STAT pathway either by direct interaction with activated JAKs or with the receptors. These interactions are mediated at least in part by the SH2 domain of SOCS proteins but these proteins also contain a highly conserved C-terminal homology domain termed the SOCS box. Here we show that the SOCS box mediates interactions with elongins B and C, which in turn may couple SOCS proteins and their substrates to the proteasomal protein degradation pathway. Analogous to the family of F-box-containing proteins, it appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway.
Amino Acid Sequence↗
Macronutrient preference, dietary intake, and substrate oxidation among stable cirrhotic patients.
Anorexia in liver disease is common; however, its association with aberrant metabolism and the type of cirrhosis has not been considered. Dietary intake, nutritional status, fasting substrate oxidation, and macronutrient preference were examined in controls (n = 18) and 65 patients with hepatocellular (n = 31) or biliary cirrhosis (n = 34). Energy intakes were lowest in hepatocellular patients (controls: 9.0 +/- 0.48 megajoules/day compared with biliary: 7.0 +/- 0.40 MJ/day, P <.05; controls compared with hepatocellular 6.5 +/- 0.39 megajoules/day, P <.01). Triceps skinfold was lower only in hepatocellular patients (controls: 109 +/- 9.2% compared with hepatocellular 79 +/- 5.6%, P <.05). The fasting rate of lipid oxidation was elevated in hepatocellular patients when compared with controls and biliary patients (controls: 40.9 +/- 15.1 mg/min compared with hepatocellular 62.8 +/- 16.8 mg/min, P <.001, and biliary : 45.5 +/- 17.0 mg/min compared with hepatocellular, P <.001). Control subjects exhibited a greater preference for the high fat, moderate carbohydrate food (controls: median 7.0 IQR 2.0 compared with biliary: median 5.0 interquartile range [IQR] 4.7, P <.01) (controls compared with hepatocellular: median 6.0 IQR 4.0, P <.01). Cirrhotic patients' spontaneous dietary intake is lower than that of controls and recommended intakes. Although macronutrient preference ratings were different within cirrhotic patient groups it remains unclear whether associated nutrient deficits are metabolically driven and dictated by primary cause.
Diet Records↗
Suppressors of cytokine signaling (SOCS): negative regulators of signal transduction.
SOCS-1 was originally identified as an inhibitor of interleukin-6 signal transduction and is a member of a family of proteins (SOCS-1 to SOCS-7 and CIS) that contain an SH2 domain and a conserved carboxyl-terminal SOCS box motif. Mutation studies have established that critical contributions from both the amino-terminal and SH2 domains are essential for SOCS-1 and SOCS-3 to inhibit cytokine signaling. Inhibition of cytokine-dependent activation of STAT3 occurred in cells expressing either SOCS-1 or SOCS-3, but unlike SOCS-1, SOCS-3 did not directly interact with or inhibit the activity of JAK kinases. Although the conserved SOCS box motif appeared to be dispensable for SOCS-1 and SOCS-3 action when overexpressed, this domain interacts with elongin proteins and may be important in regulating protein turnover. In gene knockout studies, SOCS-1(-/-) mice were born but failed to thrive and died within 3 weeks of age with fatty degeneration of the liver and hemopoietic infiltration of several organs. The thymus in SOCS-1(-/-) mice was small, the animals were lymphopenic, and deficiencies in B lymphocytes were evident within hemopoietic organs. We propose that the absence of SOCS-1 in these mice prevents lymphocytes and liver cells from appropriately controlling signals from cytokines with cytotoxic side effects.
Animals↗
A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy.
Recently intronic and exonic mutations in the Tau gene have been found to be associated with familial neurodegenerative syndromes characterized not only by a predominantly frontotemporal dementia but also by the presence of neurological signs consistent with the dysfunction of multiple subcortical neuronal circuitries. Among families, the symptomatology appears to vary in quality and severity in relation to the specific Tau gene mutation and often may include parkinsonism, supranuclear palsies, and/or myoclonus, in addition to dementia. We carried out molecular genetic and neuropathological studies on two patients from a French family presenting, early in their fifth decade, a cognitive impairment and supranuclear palsy followed by an akinetic rigid syndrome and dementia. The proband died severely demented 7 years after the onset of the symptoms; currently, his brother is still alive although his disease is progressing. In both patients, we found a Tau gene mutation in exon 10 at codon 279, resulting in an asparagine to lysine substitution (N279K). Neuropathologically, widespread neuronal and glial tau accumulation in the cortex, basal ganglia, brain stem nuclei as well as in the white matter were the hallmark of the disease. These deposits were shown by immunohistochemistry and immunoelectron microscopy, using a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes present in multiple tau regions. In the neocortex, tau-immunopositive glial cells were more numerous than immunopositive neurons; the deeper cortical layers as well as the white matter adjacent to the cortex contained the largest amount of immunolabeled glial cells. In contrast, some brain stem nuclei contained more neurons with tau deposits than immunolabeled glial cells. The correlation of clinical, neuropathological and molecular genetic findings emphasize the phenotypic heterogeneity of diseases caused by Tau gene mutations. Furthermore, to test the effect of the N279K mutation and compare it with the effect of the P301L exon 10 mutation on alternative splicing of Tau exon 10, we used an exon amplification assay. Our results suggest that the N279K mutation affects splicing similar to the intronic mutations, allowing exon 10 to be incorporated more frequently in the Tau transcript.
Adult↗
Dopamine antagonists in the orbital prefrontal cortex reduce prepulse inhibition of the acoustic startle reflex in the rat.
Schizophrenia is characterized by, among other things, (a) information processing deficits that have been indexed by a number of measures, including deficits in prepulse inhibition (PPI) of the acoustic startle reflex; and (b) pathophysiology of the frontal lobe. Recent studies have implicated the prefrontal cortex (PFC) in the modulation of PPI in rats. These studies suggest that dopamine (DA) ablation of the PFC (using 6-OHDA) leads to disruption of PPI. To better understand the role of DA type 1 (D1) and type 2 (D2) receptors in the modulation of PPI, we investigated the effects of two pharmacologically distinct DA antagonists on the modulation of PPI. Microinjection of SCH23390 (a D1 antagonist) into the orbital PFC markedly decreased PPI (at 0.1, 0.5, and 1.5 microg), whereas raclopride (a D2 antagonist) decreased PPI at some doses (0.1 and 0.5 mg/ml) but not at others (5.0 microg). We conclude that both D1 and D2 receptors mediate the cortical modulation of PPI.
Acoustic Stimulation↗
A practical approach to vascular access for hemodialysis and predictors of success.
PURPOSE: The long-term results and predictors of success for vascular access at The Toronto Hospital were studied. This report describes the access program and emphasizes the role of the vascular access coordinator. METHODS: A total of 384 consecutive patients underwent 466 vascular access procedures. The access program is centered around a dedicated, full-time vascular access coordinator, who is a registered nurse and is responsible for all aspects of access care, including follow-up. Outcome variables were collected prospectively. Primary, primary-assisted, and secondary success was determined by means of Kaplan-Meier analysis, and the stepwise Cox proportional hazards model was used for multivariate analysis of the factors that were independently predictive of primary success. RESULTS: There were 235 autogenous arteriovenous fistulae (AVFs) and 231 arteriovenous grafts (AVGs). The cumulative primary, assisted-primary, and secondary success (patent and functional for effective dialysis) at 24 months for all 466 cases combined was 36% +/- 3%, 54% +/- 3%, and 66% +/- 3%, respectively. The primary success for AVFs and AVGs at 2 years was 54% +/- 4% and 18% +/- 4%, respectively (P <.001; log-rank test); the primary-assisted success for AVFs and AVGs at 2 years was 62% +/- 4% and 44% +/- 6%, respectively (P <.001; log-rank test); and the secondary success for AVFs and AVGs at 2 years was 70% +/- 4% and 60% +/- 5%, respectively (P =.331; log-rank test). Stratification of variables revealed significant benefit for AVFs (P =.001), the female sex (P =.014), and the absence of diabetes mellitus (P =.001). Multivariate analysis with Cox regression determined that access type (AVF vs AVG; P =.001) and diabetes mellitus (P =.024) were independently predictive of primary success. The improved clinical coordination of access patients with the initiation of the vascular access program resulted in a significant reduction in length of hospital stay before and after the program was organized (2.5 +/- 0.06 vs 1.1 +/- 0.03 days; P =.001). CONCLUSION: The organization of a vascular access program in a practical and cost-effective way for reduced length of hospital stay is streamlined through a dedicated access coordinator, who ensures an integrated, multidisciplinary approach. The results for the Cox model is useful when discussing the anticipated results of access procedures with individual patients.
Algorithms↗
Developmental changes in seizure susceptibility during ethanol withdrawal.
It has recently been established that adolescence may represent a developmentally sensitive period with respect to the effects of ethanol, particularly within the NMDA neurotransmitter system. However, the same may also be true of the GABA system. There is evidence to suggest that the number of GABA receptors and their kinetics may change across development. The purpose of this study was to determine if GABA-mediated seizure susceptibility during ethanol withdrawal differed between adolescent and adult animals. Results indicate that adult animals pretreated with ethanol were more likely to achieve maximal tonic-clonic seizure activity and spent more time in stage 3 (or higher) seizure activity than all other groups. These data lend additional support to the contention that adolescent and adult animals differ in their susceptibility to the effects of ethanol and that this susceptibility is transmitter dependent.
Age Factors↗
Conditioned odor potentiation of startle in rats.
An odor previously paired with shock was shown to be an effective stimulus for potentiating the startle response in rats (Experiments 1 and 2). This effect required more than 1 odor-shock pairing (Experiment 3), was relatively long lasting (Experiment 4), and was specific to the odor previously paired with shock (Experiment 5). The implications of these findings for the startle probe procedure and for neural models of learning and memory based on results obtained with that procedure are discussed.
Animals↗
The contextual change paradox is still unresolved: comment on Bouton, Nelson, and Rosas (1999)
According to the contextual change theory of memory loss, spontaneous forgetting reflects a retrieval impairment due to subtle and unprogrammed shifts in environmental cues over a retention interval. However, Riccio, Richardson, and Ebner (1984) noted an apparent paradox in this model; specifically, laboratory studies inducing explicit shifts in contextual cues found less disruption of performance as retention intervals increased. Bouton, Nelson, and Rosas (1999) critiqued several of the claims made by Riccio et al. and concluded that the contextual cue theory is still a valid account of spontaneous forgetting. In this comment, the authors address the 3 major criticisms offered by Bouton et al., point out an inconsistency in their argument, and conclude that the original paradox still poses problems for the contextual change theory of forgetting.
Animals↗
The glenolabral articular disruption lesion: MR arthrography with arthroscopic correlation.
OBJECTIVE: The purpose of this study was to describe the MR arthrography appearance of the glenolabral articular disruption (GLAD) lesion. Proper diagnosis of this lesion is important because it can be a source of persistent shoulder pain that requires surgical repair and because it is often difficult to diagnose clinically. MATERIALS AND METHODS: Findings on MR arthrography were retrospectively correlated with the clinical histories and physical examination findings of six patients in whom we saw the typical appearance of the GLAD lesion. Four of these patients underwent follow-up arthroscopy that included surgical proof of GLAD lesions. RESULTS: Five of the six patients had a documented glenohumeral impaction injury associated with an abducted externally rotated shoulder. All six patients had persistent shoulder pain, but their shoulders were stable during routine examination. In all patients, MR arthrography showed a superficial tear of the anteroinferior labrum with an adjacent articular cartilage injury. The torn labrum remained firmly attached to the anterior scapular periosteum, and contrast material was seen to extend into the labral tear and cartilaginous defect. CONCLUSION: The MR arthrography findings of GLAD lesions include a nondisplaced tear of the anteroinferior labrum with an adjacent chondral injury. The pattern of chondral injury can range from a cartilaginous flap tear to a depressed osteochondral injury of the articular cartilage and underlying bone.
Adult↗
Implementing evidence-based practice.
Traditional methods of disseminating research findings through publication has had only a limited impact on clinical practice. Issues of time and professional territorialism may be barriers to change. More active interventions are needed to ensure that findings are implemented.
Attitude of Health Personnel↗
Opiates transdeactivate chemokine receptors: delta and mu opiate receptor-mediated heterologous desensitization.
An intact chemotactic response is vital for leukocyte trafficking and host defense. Opiates are known to exert a number of immunomodulating effects in vitro and in vivo, and we sought to determine whether they were capable of inhibiting chemokine-induced directional migration of human leukocytes, and if so, to ascertain the mechanism involved. The endogenous opioid met-enkephalin induced monocyte chemotaxis in a pertussis toxin-sensitive manner. Met-enkephalin, as well as morphine, inhibited IL-8-induced chemotaxis of human neutrophils and macrophage inflammatory protein (MIP)-1alpha, regulated upon activation, normal T expressed and secreted (RANTES), and monocyte chemoattractant protein 1, but not MIP-1beta-induced chemotaxis of human monocytes. This inhibition of chemotaxis was mediated by delta and micro but not kappa G protein-coupled opiate receptors. Calcium flux induced by chemokines was unaffected by met-enkephalin pretreatment. Unlike other opiate-induced changes in leukocyte function, the inhibition of chemotaxis was not mediated by nitric oxide. Opiates induced phosphorylation of the chemokine receptors CXCR1 and CXCR2, but neither induced internalization of chemokine receptors nor perturbed chemokine binding. Thus, inhibition of chemokine-induced chemotaxis by opiates is due to heterologous desensitization through phosphorylation of chemokine receptors. This may contribute to the defects in host defense seen with opiate abuse and has important implications for immunomodulation induced by several endogenous neuropeptides which act through G protein-coupled receptors.
Cells, Cultured↗
An increase in extracellular glutamate is a sensitive method of detecting ischaemic neuronal damage during cranial base and cerebrovascular surgery. An in vivo microdialysis study.
All patients undergoing neurological surgery are at risk for serious complications. Ischaemic damage presenting with hemiparesis or speech difficulties occurs in up to 6% of patients undergoing cerebral bypass procedures and other complicated neurosurgical procedures. Currently available methods for detection of such damage include the use of somatosensory evoked potentials (SSEPs) and electro-encephalography (EEG). Unfortunately, these techniques have false positives and may remain normal in the presence of severe focal neurological deficits. Early detection of potential deficits may prevent or minimize damage through a change in operative or anaesthetic strategy. With the availability of several potential neuroprotective compounds, it is also possible to treat patients at risk of developing ischaemic complications if the individuals are identified early. The excitatory neurotransmitter glutamate is not only a metabolic product, but is also thought to promote ischaemia induced cell injury if released into the extracellular space. It may be a significant parameter for ischaemic brain metabolism. In this report we describe 10 patients who underwent extracranial-intracranial (EC-IC) high flow bypass procedures with routine intra-operative monitoring (IOM) as well as intra-operative in-vivo microdialysis measurement of glutamate. Our aim was to compare intra-operative microdialytic findings and IOM findings with respect to patients' early postoperative clinical courses. Three patients had significant intra-operative glutamate increases indicating ischaemia. Two of these patients awoke with a new neurological deficit (hemiparesis). Routine IOM findings were either normal or showed only transient changes during the time the glutamate levels were high. Our study shows that an increase in extracellular glutamate, as monitored by in-vivo microdialysis, is an excellent early market of neuronal damage. While our glutamate measurements were done off-line, it may be possible to get in future continuous on-line measurements to serve as an early warning system for potential ischaemic damage.
Adult↗
Effects of home-nest odors on the startle response in preweanling rats.
The present study examined the effects of a highly preferred, biologically relevant olfactory stimulus (i.e., home-nest odors) on the startle response in preweanling rats. Although the rats detected the odor (as revealed by reductions in ultrasound vocalizations) it had no effect on either the initial magnitude of the startle response or habituation of this response across 80 test trials. These results are discussed in relation to recent studies on modulation of the startle response in developing rats, the effects of olfactory stimuli on the startle response, and the pleasure-attenuation of startle in nonhuman subjects.
Animals↗
Shock sensitization of startle in rats: the role of contextual conditioning.
The role of contextual conditioning in the shock sensitization of startle effect was examined in 2 experiments with rats. Experiment 1 showed that shock sensitized the startle response only if it was given in the test context, and Experiment 2 showed that the sensitization effect was abolished in subjects preexposed to the test context. Taken together, these results show that shock sensitization of startle is mediated by contextual conditioning. The implications of this finding for using the shock sensitization of startle procedure as a model preparation for examining the neural and pharmacological bases of unconditioned fear are discussed.
Analysis of Variance↗
The role of personal tutor in nurse education: towards an understanding of practice in a college of nursing and midwifery at a particular point in time.
This paper describes an inquiry to increase understanding of the role of personal tutor in a college of nursing and midwifery. Concepts of tutor and role are discussed in relation to their historical influences and an over view is provided of the research process which included document analysis and reflective audio-taped interviews with student nurses, teachers and education managers. Five conceptual categories are identified and critically analysed in relation to personal, institutional and social contexts and the factors which influence them. The first two categories identified reflect the concepts discussed in the literature. The third category reflects the uncertainties and confusion which surround differing perceptions of the role. The fourth category suggests the misunderstandings which may occur through taking for granted apparently shared concepts. The fifth category suggests the significance of personal theory in practice and the extent to which roles are taken or made. Traditional values concerning theory and practice are thus challenged. The reflective evidence provided by the participants suggests a theory, generated by them through the meanings they give to their views and actions, concerning their roles and the situation in which they find themselves at a particular point in time.
Education, Nursing, Baccalaureate↗