Biomedical subjects
R Richardson
Publications and source records attributed to R Richardson.
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.
On the evidence. Type 2 diabetes.
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A potted history of specimen-taking.
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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.
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.
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.
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.
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.
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.
A necessary inhumanity?
It is argued that the phrase "Necessary Inhumanity" more accurately describes the alienation required of doctors in some circumstances, than do modern sanitised coinages such as 'clinical detachment.' 'Detachment' and 'objectivity' imply separation, not engagement: creating distance not only from patients, but from the self: the process may well be required, but where it becomes too extreme or prolonged, it can damage everybody, including patients, family members, doctors themselves, and wider society. An awareness of the history of health care in the context of our society might assist self reflection--might help keep initiates in touch with the culture they have been induced to leave and might help them remain humane despite the bruising process of training.
Complications of diabetes: screening for retinopathy and management of foot ulcers.
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Complications of diabetes: renal disease and promotion of self-management.
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Prevalence and causes of cough in chronic dialysis patients: a comparison between hemodialysis and peritoneal dialysis patients.
Peritoneal dialysis (PD) and hemodialysis (HD) are both common forms of dialysis for patients with end-stage renal disease. A few case reports have suggested that cough is associated with PD. From 1991 to 1998, 17 patients being treated with PD at the Toronto Western Hospital demonstrated persistent cough severe enough for referral to a respirologist. Causes of cough, often more than one cause per patient, included asthma, post-nasal drip, gastroesophageal reflux disease (GERD), chronic obstructive pulmonary disease, congestive heart failure, allergic rhinitis, pleural effusion, and respiratory infection. The aim of this cross-sectional study was to establish the prevalence of cough among PD patients, to determine if PD patients more commonly have a dry persistent cough than do HD patients, and, if the latter case is true, the possible reasons for it. A detailed survey of 92 PD patients and 91 HD patients was conducted in 1998 and 1999 at the University Health Network. Survey questions inquired about patient respiratory symptoms since onset of dialysis. Charts were reviewed to obtain information on use of medications possibly relevant to cough. In the PD and HD groups, 52% and 23% were females (p = 0.001), and the mean ages were 59.1 and 60.1 years, respectively. Angiotensin converting enzyme (ACE) inhibitors had been taken by 65% (PD) and 55% (HD) of patients, and beta-blocking medications by 43% (PD) and 51% (HD). Since initiation of dialysis--mean 2.7 years (PD) and 3.7 years (HD)--22% of PD patients reported persistent cough versus 7% of HD patients (p = 0.003). Although no significant association was seen between cough and self-reported heartburn in HD patients (p = 0.439), a significant association between cough and self-reported heartburn was seen in PD patients: 67% of PD patients with persistent cough reported heartburn versus 29% of those without cough (p = 0.008). The findings suggest that GERD and associated cough are more common in PD patients than in HD patients, perhaps owing to increases in intra-abdominal pressure from the peritoneal dialysate.
The ontogeny of conditioned odor potentiation of startle.
During development, conditioned responses usually occur first to olfactory, then to auditory, and finally to visual cues. The authors of the present study report that fear potentiation of startle to an olfactory conditioned stimulus emerges relatively late in development (i.e., at 23 days of age; Experiments 1 and 2). The failure to observe conditioned odor potentiation of startle (OPS) in younger rats was not due to a failure to either acquire or remember the odor-shock association (Experiment 3). Surprisingly, the authors also found that rats trained at 16 but tested at 23 days of age failed to exhibit the OPS effect even though they did exhibit pronounced odor avoidance (Experiment 4). The results are discussed in terms of (a) sensory-specific sequential emergence of learned fear, (b) the neural circuit involved in fear potentiation of startle, and (c) the concept that conditioned responding is appropriate to the animal's age at the time of training rather than its age at testing.
Transplanting teeth.
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On the evidence. Smoking prevention.
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