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Biomedical subjects

R Richardson

Publications and source records attributed to R Richardson.

At least 19 recordsLinked to original sources

Carbachol injections into the nucleus accumbens disrupt acquisition and expression of fear-potentiated startle and freezing in rats.

The nucleus accumbens is involved in different types of emotional learning, ranging from appetitive instrumental learning to Pavlovian fear conditioning. In previous studies, we found that temporary inactivation of the nucleus accumbens blocked both the acquisition and expression of conditioned fear. This was not due to altered dopaminergic activity as we have also found that intra-nucleus accumbens infusions of the dopamine agonist amphetamine do not affect either the acquisition or the expression of conditioned fear. Therefore, in the present study we examined whether cholinergic activity in the nucleus accumbens is involved in the acquisition and expression of conditioned fear. Specifically, the effect of intra-nucleus accumbens infusions of the unselective cholinergic agonist carbachol on the acquisition and expression of conditioned fear was assessed. Across several experiments, we measured fear to visual and acoustic conditioned stimuli and to the experimental context. Further, two different measures of conditioned fear were recorded: fear potentiation of startle and freezing. Intra-nucleus accumbens carbachol infusions disrupted acquisition as well as expression of conditioned fear, regardless of the modality of the fear-eliciting stimulus or of the specific measure of conditioned fear. This disruption of conditioned fear was not simply a by-product of enhanced motor activity which also occurred after intra-nucleus accumbens carbachol infusions. Interestingly, despite the substantial effect of intra-nucleus accumbens carbachol on expression of conditioned fear, the results of the final experiment suggest that these rats extinguish similarly to control rats. Taken together, the present results indicate that acetylcholine within the nucleus accumbens is important for the learning and retrieval of conditioned fear.

Acetylcholine↗

Probability of early pregnancy loss in women with vaginal bleeding and a singleton live fetus at ultrasound scan.

Bleeding is a common feature of early pregnancy affecting about one-fifth of pregnant women in the first trimester. The chance of miscarriage after bleeding and a live fetus at scan has not previously been defined precisely. The purpose of this study was to evaluate the outcome of early pregnancies with a viable singleton fetus that had been complicated by bleeding. A prospective study was performed on 370 women with a singleton live fetus who had presented to the early pregnancy assessment clinic (EPAC) with vaginal bleeding. Women were grouped into light, moderate and heavy loss according to the self-assessed degree of vaginal bleeding. The women were also categorised according to the presence or absence of an intrauterine haematoma. The overall spontaneous miscarriage rate in the study was 11.1%; almost 90% of pregnancies continued to viability. Women with moderate or heavy bleeding had more than twice the rate of miscarriage compared with those with light bleeding. A total of 14% of the women had an intrauterine haematoma and those women were 2.6 times more likely to miscarry than those without (23% vs 9%). This relationship appeared to hold true even after controlling for blood loss. The data presented can be used to guide women with a live fetus about the chance of miscarriage after an episode of vaginal bleeding. We propose that a large multi-centre study should be undertaken to define precisely the risk miscarriage for each gestational week according to a range of clinical and ultrasound characteristics.

Abortion, Spontaneous↗

Transcription and mass-spectroscopic proteomic studies of electron transport oxidoreductases in Dehalococcoides ethenogenes.

Besides 19 potential reductive dehalogenase genes, the genome of Dehalococcoides ethenogenes strain 195 contains over 60 genes annotated as encoding oxidoreductases, including five hydrogenase complexes and a formate dehydrogenase (Fdh). Using quantitative reverse transcriptase polymerase chain reaction, we found that genes encoding a periplasmic Hup hydrogenase and the Fdh were the most highly expressed in batch-grown pure cultures, in which the H2 partial pressure was >0.1 atm, and in butyrate/tetrachloroethene-mixed cultures, in which H2 partial pressures were 10(-4)-10(-5) atm. Shotgun electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry were used to identify multiple peptides in pure culture membrane-enriched fractions matching several highly expressed respiratory enzymes, including three hydrogenases, two reductive dehalogenases, Fdh and DET1407, a 105.5-kDa protein we propose to be part of an S-layer cell wall. Both transcript and mass spectrometric approaches indicated that the putative Fdh was an important oxidoreductase in these cells; nevertheless, D. ethenogenes cultures could not use formate as an electron donor for reductive dechlorination. Analysis of the gene encoding the large subunit of Fdh indicated that while it was related to other Fdh proteins, its sequence encodes serine rather than cysteine or selenocysteine at a critical position, casting doubt on its function. Overall, genomic and proteomic approaches have provided novel insights into the metabolism of this difficult to culture organism.

Bacterial Proteins↗

Biomarkers of drug-induced vascular injury.

In pre-clinical safety studies, drug-induced vascular injury is an issue of concern because there are no obvious diagnostic markers for pre-clinical or clinical monitoring and there is an intellectual gap in our understanding of the pathogenesis of this lesion. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary targets, smooth muscle and endothelial cells are unknown. However, evaluation of novel markers for potential clinical monitoring with a mechanistic underpinning would add value in risk assessment and management. This mini review focuses on the progress to identify diagnostic markers of drug-induced vascular injury. Von Willebrand factor (vWF), released upon perturbation of endothelial cells, is transiently increased in plasma prior to morphological evidence of damage in dogs or rats treated with vascular toxicants. Therefore, vWF might be a predictive biomarker of vascular injury. However, vWF is not an appropriate biomarker of lesion progression or severity since levels return to baseline values when there is morphological evidence of injury. A potential mechanistically linked biomarker of vascular injury is caveolin-1. Expression of this protein, localized primarily to smooth muscle and endothelial cells, decreases with the onset of vascular damage. Since vascular injury involves multiple mediators and cell types, evaluation of a panel rather than a single biomarker may be more useful in monitoring early and severe progressive vascular injury.

Animals↗

Ozone therapy for the treatment of dental caries.

BACKGROUND: Dental caries is a bacterially mediated disease characterised by demineralisation of the tooth surface, which may lead to cavitation, discomfort, pain and eventual tooth loss. Ozone is toxic to certain bacteria in vitro and it has been suggested that delivering ozone into a carious lesion might reduce the number of cariogenic bacteria. This possibly could arrest the progress of the lesion and may, in the presence of fluoride, perhaps allow remineralisation to occur. This may in turn delay or prevent the need for traditional dental conservation by 'drilling and filling'. OBJECTIVES: To assess whether ozone is effective in arresting or reversing the progression of dental caries. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (to 7 November 2003); Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003); MEDLINE and PREMEDLINE (OVID, 1966 to November 2003); EMBASE (OVID, 1980 to November 2003); CINAHL (OVID, 1982 to November 2003); AMED (OVID, 1985 to November 2003). Quintessence was handsearched through 2002 and KaVo were contacted as manufacturers of the HealOzone apparatus for any additional published or unpublished trials. SELECTION CRITERIA: Inclusion was assessed independently by at least two reviewers. Trials were only included if they met the following criteria: randomisation in a controlled trial; single surface in vivo carious lesion accessible to ozone application; clear allocation concealment; ozone application to the lesions in the intervention group; no such application of ozone in the control group; outcomes measured after at least 6 months. DATA COLLECTION AND ANALYSIS: Reviewers independently extracted information in duplicate. A paucity of comparable data did not allow meta-analytic pooling of the included studies. MAIN RESULTS: Three trials were included, with a combined total of 432 randomised lesions (137 participants). Forty-two conference papers, abstracts and posters were excluded (from an unknown number of studies). The risk of bias in all studies appeared high. The analyses of all three studies were conducted at the level of the lesion, which is not independent of the person, for this reason pooling of data was not appropriate or attempted. Individual studies showed inconsistent effects of ozone on caries, across different measures of caries progression or regression. Few secondary outcomes were reported, but one trial reported an absence of adverse events. REVIEWERS' CONCLUSIONS: Given the high risk of bias in the available studies and lack of consistency between different outcome measures, there is no reliable evidence that application of ozone gas to the surface of decayed teeth stops or reverses the decay process. There is a fundamental need for more evidence of appropriate rigour and quality before the use of ozone can be accepted into mainstream primary dental care or can be considered a viable alternative to current methods for the management and treatment of dental caries.

Cariostatic Agents↗

Pharmacological properties of l-glutamate receptors associated with the crayfish hindgut.

Pharmacological agents were used to characterize glutamate receptors associated with crayfish hindgut. l-Glutamate reliably increased tonus in isolated hindguts of Procambarus clarkii and suppressed spontaneous hindgut contractions at concentrations of 10 micromol l(-1) or higher. Quisqualate and ibotenate mimicked the effects of L-glutamate. Experiments with strips and rings of hindgut tissue indicate that glutamate acts on both circular and longitudinal muscles. Hindgut contractions were not affected by (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionoic acid, N-methyl- d-aspartate, domoate or the metabotropic glutamate receptor agonist, (1S,3R)-1-amino-1-carboxycyclopentane-3-acetic acid. Picrotoxin, at 50 micromol l(-1), did not alter the ibotenate-induced reduction in contraction frequency, suggesting that this effect is not produced by inhibitory glutamate receptors. The glutamate-induced increase in tonus was antagonized by Joro spider toxin, JSTX-3. Thus, glutamate receptors associated with crayfish hindgut muscles are of the quisqualate type but are also sensitive to ibotenate. Elevating extracellular potassium concentration mimicked all of the effects of glutamate, suggesting that excessive depolarization may contribute to the suppression of contractions at high agonist concentrations.

Animals↗

Anaphylaxis from topical bovine thrombin (Thrombostat) during haemodialysis and evaluation of sensitization among a dialysis population.

BACKGROUND: Topical bovine thrombin (TBT) is used as a topical haemostatic agent in haemodialysis (HD) units and for surgical procedures. It has caused allergic reactions during surgical procedures, but no previous cases have been reported with dialysis usage. OBJECTIVE: A case is reported of anaphylaxis due to TBT in an HD patient. This led to a determination of whether HD patients exposed to TBT develop specific IgE and IgG antibodies to TBT and an assessment of the frequency of allergic symptoms in HD patients as compared with peritoneal dialysis (PD) patients. METHODS: A cross-sectional study of 100 HD and 52 PD patients was performed using a questionnaire to determine allergic symptoms. An ELISA assay was developed to determine TBT-specific IgE and IgG serum antibodies among HD patients. HD patients without TBT exposure and age- and gender-matched blood donors served as controls. RESULTS: Allergic symptoms temporally related to dialysis reported by a questionnaire were significantly more frequent for HD patients than for PD patients: rhinoconjuctivitis 11% vs. 2%, asthma symptoms 20% vs. 6%, urticaria 23% vs. 8% (P values <0.05). Positive TBT-specific IgE and IgG antibodies were more frequent among 65 exposed HD patients (28% for IgE and 26% for IgG) than for controls (4% and 9%), P<0.05. CONCLUSIONS: Results indicate the potential for sensitization and clinical allergic responses to beef thrombin when used for haemostasis in HD and suggest that other haemostatic methods should be considered.

Adult↗

Keats's notebook.

Explore the source record for details and available documents.

Education, Medical↗

Centrally administered corticotropin-releasing hormone and peripheral injections of strychnine hydrochloride potentiate the acoustic startle response in preweanling rats.

Attempts to condition fear potentiation of startle (FPS) in rats younger than 23 days of age have not been successful, regardless of the type of aversively conditioned stimulus used (P. S. Hunt, R. Richardson, & B. A. Campbell, 1994; R. Richardson, G. Paxinos, & J. Lee, 2000; R. Richardson & A. Vishney, 2000). In the present study, the authors report that peripheral injections of strychnine hydrochloride, a glycine receptor antagonist, and intracerebroventricular infusions of corticotropin releasing hormone (CRH) both potentiated the acoustic startle response (ASR) in 16-18-day-old rats. Because strychnine and CRH have distinct sites of activation in the primary startle pathway, it can be concluded that this pathway is functional and modifiable in rats younger than 23 days of age. This finding suggests that the failure to observe conditioned FPS in preweanling rats is due to an immaturity of the secondary fear circuit responsible for enhancing the ASR during a fear state.

Age Factors↗

The profile of substance-using pregnant mothers and their newborns at a regional rural hospital in New South Wales.

We conducted an audit study of identified substance-using mothers and their neonates at Lismore Base Hospital in the Northern Rivers region of New South Wales between January 1995 and December 1999. Women using marijuana and/or alcohol only were excluded. The average number of total births during the study period was 1,363 per year. Forty-nine mothers were identified as substance users with an incidence of seven per 1,000 total births. Twenty-three (47%) were methadone users, 14 (29%) methadone and intravenous heroin users, 11 (22%) heroin users, and one (2%) used amphetamines. Twenty-seven (55%) had irregular antenatal visits. Forty-one (89%) were hepatitis C positive. Forty-seven neonates were live-born and there were two stillbirths. Thirty-seven (79%) required admission to the special care nursery, 40% of them for withdrawal alone. Twenty-seven (55%) babies had neonatal withdrawal and 23 (49%) required medication for withdrawal. The incidence of substance abuse among the pregnant women in this region is ten times higher than the previously quoted figures in metropolitan areas of Australia.

Adolescent↗

Performance-related pay in health care.

OBJECTIVE: Performance-related pay (PRP) has been widely extended within the British public sector in the last 15-20 years, mostly because of pressure from central government. Its penetration in the National Health Service (NHS) has not so far been very deep but it has been sufficient to permit preliminary judgements on its likely impact. METHODS: Review of published accounts of the extent of use of PRP in the NHS and its impact, plus two case studies. RESULTS: There have been few rigorous studies reported. PRP has been introduced for a variety of reasons: an incentive to motivate staff; to enhance staff recruitment and retention; to signal a change in organizational culture; to control staff costs; to reduce the power of trades unions; to reinforce staff development policies. Very few NHS provider organizations have implemented PRP. Despite this, senior managers see real merit in it in improving staff performance and delivering a clear message about the importance of organizational performance. Employees are much more skeptical, seeing PRP as having no effect or being detrimental. CONCLUSIONS: PRP has had, at most, only a very modest beneficial impact in the British NHS. In the absence of better evidence, it would be sensible for government to continue to encourage local initiatives rather than propose a mandatory national scheme. It would also be prudent to subject local schemes to rigorous evaluation.

Employee Incentive Plans↗