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Biomedical subjects

R Richardson

Publications and source records attributed to R Richardson.

At least 19 recordsLinked to original sources

Keats's notebook.

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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↗

Shock sensitization of startle: learned or unlearned fear?

Following shock, rats exhibit a potentiated startle response to a sudden, loud noise. It has been suggested that this shock sensitization of the startle response can be used as a model preparation for studying unlearned fear. After reviewing the theoretical and empirical bases for this claim, the results of several recent studies that show that the shock sensitization of startle effect is actually mediated by contextually conditioned fear are presented. From this, it is concluded that the shock sensitization of startle procedure is an appropriate model preparation for studying contextual conditioning but is not an appropriate procedure for studying unlearned fear. Several other procedures that have potential as model preparations for studying unlearned fear are discussed briefly.

Animals↗

Shock sensitization of startle in the developing rat.

Rats given a series of shocks exhibit a potentiated startle response to a loud acoustic stimulus compared to nonshocked animals. Experiment 1 showed that this shock sensitization of startle, like conditioned fear potentiation of startle to discrete cues, emerges relatively late in development (i.e., 23 days of age). Although different testing procedures were used in Experiment 2, preweanling rats still failed to exhibit the shock sensitization of startle effect. The failure to observe the shock sensitization of startle effect in preweanling rats was not due to age differences in contextual conditioning produced by the shock treatment (Experiment 3). The results of this study are discussed in terms of (a) the emergence of fear potentiation of startle during development, and (b) the relation between conditioned freezing and startle potentiation.

Acoustic Stimulation↗

Conditioned changes in ultrasonic vocalizations to an aversive olfactory stimulus are lateralized in 6-day-old rats.

Using a soft rubber plug to block airflow in one naris, Kucharski, Johanson, and Hall (1986) found that some forms of olfactory memory (e.g., odor preferences) were lateralized in young rats while other forms (e.g., conditioned activation and mouthing) were not. The present experiments extended that research by showing that conditioned increases in ultrasonic vocalizations were also lateralized. That is, when exposed to an odor that was previously paired with footshock, 6-day-old rats significantly increased their rate of vocalizing. This response only occurred, however, when the naris open at training was also open at test. The use of the developing rat as a natural split-brain preparation appears to be an effective procedure with which to broaden current approaches to the analysis of learning, memory, and emotion.

Age Factors↗

Effects of environmental enrichment on rate of contextual processing and discriminative ability in adult rats.

The effect of environmental enrichment on conditioned freezing to contextual cues in adult Sprague-Dawley rats was examined. The freezing of both enriched-and standard-reared rats increased with the time spent in the chamber prior to shock. Both groups of rats showed equally low levels of contextual conditioning following a preshock period of 4 s and equally high levels following a 120-s preshock period. However, following a preshock period of 16 s enriched rats displayed more contextual conditioning than standard rats. That is, enriched rats appeared to process contextual information faster than their standard-reared counterparts. Enriched- reared rats also showed a greater ability to discriminate between the conditioning context and a similar but distinctive context. Hence, in addition to forming a representation of the context in memory more rapidly than standard-reared rats, enriched-reared rats also appear to form a more complex representation.

Age Factors↗

Effects of multisensory environmental stimulation on contextual conditioning in the developing rat.

The effect of increased exposure to multisensory stimulation during development on conditioned freezing to contextual cues in preweanling Sprague-Dawley rats was examined. Rats given increased environmental stimulation exhibited long-term contextual conditioning at a younger age than rats that did not receive such stimulation when there was either low or moderate levels of conditioning (Experiments 1 and 2). These differences in contextual conditioning were not a result of the stimulated rats reacting differently to shock (Experiment 4) or merely freezing more than the nonstimulated rats in all situations (Experiment 3). The role of the glucocorticoid system in the enhanced contextual learning of stimulated preweanling rats and the advantages of the contextual conditioning procedure for studying the effects of environmental stimulation are discussed.

Animals↗

Neuroserpin mutation S52R causes neuroserpin accumulation in neurons and is associated with progressive myoclonus epilepsy.

Mutations in the Neuroserpin gene have been reported to cause familial presenile dementia. We describe a new family in which the S52R Neuroserpin mutation is associated with progressive myoclonus epilepsy in 2 siblings. The proband presented myoclonus and epilepsy at age 24, his brother and mother presented a similar disorder when they were 25. A clinical diagnosis of progressive myoclonus epilepsy was made on the proband and his brother. Skin and liver biopsies did not reveal the presence of cytological alterations in the proband. His neurological status worsened over the subsequent 19 yr during which he became demented and had uncontrollable seizures. He died at 43 yr of age from aspiration pneumonia. Neuropathologically, eosinophilic bodies, which were positive for periodic acid-Schiff and immunoreactive with antibodies against human neuroserpin, were present in the perikarya and cell processes of the neurons. They were found in large numbers in the cerebral cortex and substantia nigra and to a lesser extent, in most subcortical gray areas, spinal cord, and dorsal root ganglia. By electron microscopy, the intracytoplasmic bodies were contained within the membranes of the rough endoplasmic reticulum. Occasionally neuroserpin immunopositivity was seen throughout the cytoplasm, even without the presence of well-defined bodies. Our study characterizes for the first time the neuropathologic phenotype associated with hereditary progressive myoclonus epilepsy caused by the S52R Neuroserpin mutation.

Adult↗

Energy expenditure in acetaminophen-induced fulminant hepatic failure.

OBJECTIVE: To determine energy expenditure in critically ill patients suffering from acetaminophen-induced fulminant hepatic failure and compare it with values obtained in matched, healthy control subjects and in patients studied during the anhepatic period of elective liver transplantation. DESIGN: Prospective, controlled, observational study. SETTING: A ten-bed intensive therapy unit and a liver transplant unit at a University teaching hospital. PATIENTS AND SUBJECTS: Sixteen patients suffering from acetaminophen-induced fulminant hepatic failure who were sedated, paralyzed, and mechanically ventilated; 16 age-, gender-, and weight-matched, awake, healthy control subjects; and 16 patients with chronic liver disease, undergoing elective liver transplantation, who were studied during the anhepatic period of surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean energy expenditure was calculated in each case for a 30-min period, using indirect calorimetry. In the patients undergoing liver transplantation, measurements were performed after clamping the hepatic veins and recipient hepatectomy. Energy expenditure was markedly increased in the fulminant hepatic failure group (mean energy expenditure, 4.05 [SD 0.52] kJ x kg(-1) x hr(-1)), in comparison with healthy control subjects (mean, 3.44 [0.27] kJ x kg(-1) x hr(-1); mean difference, 18%; p < .001) and in comparison with patients during the anhepatic period of liver transplantation (mean, 3.15 [0.61] kJ x kg(-1) x hr(-1); mean difference, 29%; p < .001). These differences were even more pronounced when a correction factor for differences in core temperature was included in the calculation. Harris-Benedict predictions of energy expenditure were unreliable in the patients with acute liver failure. No correlations were found among energy expenditure and hemodynamic variables, the requirement for vasoconstrictors, or the presence of renal failure. CONCLUSIONS: Despite the loss of functioning liver cell mass, the metabolic rate is substantially increased in patients with acetaminophen-induced fulminant hepatic failure. This finding is consistent with the marked systemic inflammatory response, which accompanies acute hepatic failure. The Harris-Benedict equation is unreliable when an estimation of energy expenditure is required in patients with this condition.

Acetaminophen↗