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Biomedical subjects

T Garrick

Publications and source records attributed to T Garrick.

At least 19 recordsLinked to original sources

Brain donation for research: who donates and why?

Understanding what influences people to donate or not donate body organs is critical for the future of transplant surgery and medical research. Are people involved with a brain donor program for research influenced by the same factors, and are they also donors for organ transplantation? Using web-based technology, people involved in an Australian brain donation program (for research) were asked to complete a questionnaire designed to elicit demographic information, motivational factors and information about involvement in organ transplantation programs. The response rate was 82%. The majority of people involved in the program are young, well-educated Australian females. Seventy-eight percent are involved in other organ and tissue donation programs. People involved in the 'Using our Brains' program are the same group as those who are organ and tissue donors. An improvement in the overall donation rate might be possible if the resources of the research and transplant organisations were combined.

Adolescent↗

Characterization of gabaergic neurons within the human medial mamillary nucleus.

The morphology, distribution and relative frequency of GABAergic neurons in the medial mamillary nucleus (MMN) of normal human individuals was studied using a glutamic acid decarboxylase (GAD) antiserum. GAD-immunoreactive (GAD-IR) neurons were found sparsely distributed throughout the MMN and most displayed a simple bipolar morphology. A small population of large diameter GAD-IR neurons was found in the white matter capsule adjacent to the ventral border of the MMN. Results of double-labeling experiments revealed no evidence of calretinin, parvalbumin or calbindin immunoreactivities co-localizing with GAD-IR neurons. GAD-IR neurons of the MMN had an average somal area of 138+/-41 microm2, compared with the average somal area of 384+/-137 microm2 for the population of MMN neurons as a whole. GAD-IR neurons had a tendency to cluster in groups of two (and occasionally three) and showed a distribution gradient across the MMN with higher densities being found near the insertion of the fornix, the origin of the mamillo-thalamic tract and toward the medial MMN border. Quantitative estimates of GAD-IR neuron frequency revealed the GAD-IR phenotype to constitute an average of 1.7% percent of the total neuron population within the human MMN. These findings suggest that inhibitory activity within the human MMN is regulated in part by a small population of intrinsic GABAergic interneurons.

Adult↗

Stress-induced enhancement of auditory startle: an animal model of posttraumatic stress disorder.

An innovative animal model of posttraumatic stress disorder (PTSD) is proposed in which nonhabituation of the acoustic startle response is developed in rats subsequent to tailshock exposure. Subjects (n = 31) received 30 minutes of intermittent tail shock on 2 days followed by exposure to the tailshock apparatus on the third day. Compared to baseline startle reactions, 9 of 31 tailshock-exposed rats developed nonhabituation of startle response reactions during the subsequent 3 weeks of testing. No control rats developed nonhabituation of startle reactions over a similar time period. These data suggest that this system models useful aspects of clinical PTSD emphasizing nonhabituation of startle reactions as a dependent variable. The method consistently identifies a subgroup of rats that develop persistent nonhabituation of startle in response to a tailshock-stress paradigm.

Animals↗

Actuarial risk assessment models: a review of critical issues related to violence and sex-offender recidivism assessments.

Risk assessment in the area of identification of violence has been dichotomized by several prominent researchers as the "clinical approach" versus the "actuarial method". The proponents of the actuarial approach argue for actuarially derived decisions to replace existing clinical practice. The actuarial method requires no clinical input, just a translation of the relevant material from the records to calculate the risk score. A risk appraisal approach based upon a sole actuarial method raises several questions: those of public safety, peer-accepted standards of practice, liability issues, and concordance with evidence-based medicine practice. We conclude that the sole actuarial approach fails to satisfy these critical issues.

Actuarial Analysis↗

Size of mamillary bodies in health and disease: useful measurements in neuroradiological diagnosis of Wernicke's encephalopathy.

BACKGROUND: As the resolution of noninvasive neuroimaging techniques improves, small structures such as the mamillary bodies can be visualized and measured. The mamillary bodies are pathologically small in a number of neurological disorders, the most common and important is chronic Wernicke's encephalopathy (WE), or the Wernicke-Korsakoff syndrome (WKS), as it is often called. This disorder is caused by vitamin B1 deficiency (thiamin) and is seen most commonly in people who drink excessive amounts of alcohol. The disorder is easily preventable by using oral or parenteral thiamin. The aim of this study was to establish a range for the volume of the mamillary bodies in normal and in various disease states, particularly WE. METHODS: Brains were taken from 2212 sequential autopsies performed at the New South Wales Institute of Forensic Medicine from 1996 through 1997. After fixation in 10% formalin, the brains were sectioned coronally and a block containing the mamillary bodies was dissected. The maximum vertical and transverse diameters of the mamillary bodies were measured using Mitutoyo vernier callipers and the volume calculated (V = 4/3 (a2b), where a and b are the vertical and transverse radii, respectively). RESULTS: There were 164 cases with significant pathological changes in the mamillary bodies. These included cases with WE (25), Alzheimer's discase (10), infarction (11), and trauma (55). All but two of the WE cases were chronic or acute on chronic. The mean volume of the mamillary bodies was reduced by 60% in cases with chronic WE and by 25% in cases with Alzheimer's disease. In normal cases, there was a significant age-related reduction in volume, and males had larger mamillary bodies than females. Cases with alcoholic cirrhosis of the liver had normal mamillary body volumes. CONCLUSIONS: There is a gross shrinkage of the mamillary bodies in cases of chronic WE, but clinicians need to consider other diagnoses, such as Alzheimer's disease, which can also result in shrinkage. These quantitative data will be helpful in the neuroradiological diagnosis of some of these disorders, particularly WE.

Adolescent↗

Psychophysiologic parameters of traumatic stress disorder in rats.

Nonhabituation of the acoustic startle response is used to identify rat subjects with altered alarm responses subsequent to trauma exposure. Subjects (n = 31) were exposed to 30 minutes of intermittent tail shock on 2 days followed by exposure to the apparatus on the third day. Twenty-nine percent of traumatized rats developed nonhabituation of startle over the subsequent 3 weeks of testing. No control rats developed nonhabituation of startle reactions over a similar time period. These data suggest that this system represents a more accurate representation of clinical PTSD than do other animal models.

Animals↗

Effects of intermittent tail shock or water avoidance on proximal colonic motor contractility in rats.

Changes in proximal colonic mechanical activity and defecation during exposure to three different types of experimental stressors were examined in rats chronically implanted with 2 force transducers on the proximal colon. To validate the integrity of the recording system, meal-induced changes in proximal colonic contractility were initially measured in all rats 1-2 days prior to stress induction. Different groups of ad lib fed rats were then exposed to tail shock, re-exposure to the shock chamber or water avoidance for 1 h over the next 1-2 days. Two types of phasic colonic contractions, long (0-3/min) and short (6-8/min) duration, were analyzed separately using a computer. Long duration contractions were significantly elevated 21-71% over fasting basal values from 61-120 min following a meal. No other consistent changes during the prandial or postprandial period were observed. Tail shock significantly suppressed proximal colonic contractility from pre-shock values and increased fecal output and fluid content when compared to ad lib fed rats that were not shocked. Fecal output increased but proximal colonic contractility did not change when previously shocked rats were re-exposed to the tail shock chamber but not shocked. In rats exposed to water avoidance, proximal colonic contractility was minimally suppressed but defecation was significantly greater than home cage control animals. These results indicate that proximal colonic contractile activity is differentially altered by exposure to different environmental stressors and may be a contributing factor in stress-induced bowel dysfunction.

Animals↗

Body temperature and wheel running predict survival times in rats exposed to activity-stress.

The relationship between restricted feeding, core body temperature (Tb), wheel running, survival, and gastric erosion formation was examined in female rats exposed to activity-stress. Core body temperature and gross motor activity were telemetrically monitored in four groups of rats that had free access to running wheels and in one group that was not allowed to run on the wheels. Twenty-four hours prior to the onset of hypothermia and predicted mortality, different groups were left undisturbed, warmed with a heat lamp, denied access to running wheels, or euthanized. Length of survival in wheel-running rats varied from 2 to 12 days. During the first day of food deprivation, premorbid changes in the variability of Tb during the diurnal period and the mean number of wheel revolutions during the nocturnal period were strongly predictive of length of survival. Warming rats with a heat lamp or preventing rats from ever running on the wheel increased the length of survival and attenuated gastric erosion formation. Only rats that were warmed had a greater likelihood of survival. Gastric pathology was also reduced in rats that were euthanized prior to becoming moribund. Rats that were left undisturbed or locked from the running wheel over the last 24 h of testing became moribund and had extensive gastric mucosal damage. These results indicate that thermoregulatory disturbances induced by restricted feeding and not wheel running alone are critical in determining survival and the degree of gastric mucosal injury in rats exposed to activity-stress. Results further suggest that predisposing factors may put some rats at risk for the development of activity-stress-induced mortality.

Animals↗

Microinjection of thyrotropin-releasing hormone analogue into the central nucleus of the amygdala stimulates gastric contractility in rats.

The effect on gastric contractility following bilateral microinjection of thyrotropin-releasing hormone (TRH) analog, RX 77368, into the central nucleus of the amygdala was examined in fasted, urethane-anesthetized rats. Extraluminal force transducers were used to measure gastric corpus contractility. Bilateral microinjection of RX 77368 (0.5 microgram, 1.0 microgram, n = 6 each) stimulated gastric contractility for up to 120 min post-injection, P < 0.05. Gastric contractility was not significantly stimulated by microinjection of 0.1 microgram RX 77368, 0.1% bovine serum albumin (BSA) into the central nucleus or RX 77368 (0.5 microgram, 1.0 microgram) into sites adjacent to the central nucleus. Peak responses (1.0 microgram) occurred 40 min post-injection and represented a 16-26-fold increase over basal values. The frequency of gastric contraction waves was attenuated for 0-90 min in rats receiving central amygdaloid microinjection of RX 77368 (0.1, 0.5 or 1.0 microgram) versus rats microinjected with the vehicle or RX 77368 into sites adjacent to the central nuclei. The stimulatory effect of RX 77368 (1.0 microgram) on gastric contractility was abolished by subdiaphragmatic vagotomy. These results indicate that the TRH analog, RX 77368, acts within the central amygdala to vagally stimulate gastric contractility.

Amygdala↗

Interleukin-1 beta in the dorsal vagal complex inhibits TRH analogue-induced stimulation of gastric contractility.

The effect of murine interleukin-1 beta (mIL-1 beta) microinjected into the dorsal vagal complex (DVC) on thyrotropin-releasing hormone (TRH) analogue (RX-77368)-induced stimulation of gastric contractility was examined in fasted, urethan-anesthetized rats. Gastric corpus contractions were measured with extraluminal force transducers and analyzed by computer. Microinjection of RX-77368 (30 ng) into the right DVC with mIL-1 beta microinjected either into the right (100, 250 pg) or into the left (100, 500 pg) DVC inhibited gastric contractility for 30-120 min postinjection. Peak suppression of gastric contractility (64-78%) occurred at 50-60 min postinjection. Microinjection of mIL-1 beta into the DVC at a lower dose (10 pg) or into sites adjacent to the DVC (100-500 pg) did not suppress the stimulated gastric contractility pattern. Injection of mIL-1 beta (250 pg) or 0.1% bovine serum albumin into the DVC alone did not alter basal gastric contractility. Intracisternal injection of the IL-1 receptor antagonist (250 ng/10 microliters) abolished the inhibitory effect of mIL-1 beta (250 pg) on gastric contractility. These results demonstrate that mIL-1 beta acts in the DVC to inhibit vagally stimulated gastric contractility, and its action is mediated by IL-1 receptors.

Animals↗

Is liability possible for forensic psychiatrists?

Forensic psychiatrists are not as vulnerable to liability as general psychiatrists. The absence of a traditional physician-patient relationship and judicial and quasijudicial immunity are all protective against malpractice actions. Although the absence of a doctor-patient relationship removes an essential element of malpractice, other types of liability such as defamation and ordinary negligence are possible and may not be covered by malpractice insurance. A model is proposed for forensic psychiatry of a partial secondary doctor-patient relationship out-weighted in most circumstances by duties to truth and/or the hiring attorney. Such a model seems most consistent with conflicting duties currently forced on all psychiatrists. This model has advantages of a duty, a violation of which is likely to be covered by malpractice insurance. Rather than deemphasizing partial secondary physician-patient responsibilities, it is advised to stress the important protection provided by judicial and quasijudicial immunity.

Forensic Psychiatry↗

Microinjection of thyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus stimulates gastric contractility.

Changes in gastric contractility following microinjection of thyrotropin-releasing hormone (TRH) into the paraventricular nucleus of the hypothalamus (PVN) were examined in fasted, urethane-anesthetized rats. Gastric contractility was measured with extraluminal force transducers and analysed by computer. Unilateral and bilateral PVN microinjections of TRH (0.5 and 1.0 microgram) significantly increased the force index of gastric contractions from 0 to 60 min postinjection, when compared with animals microinjected with 0.1 microgram TRH, 0.1% BSA or TRH (0.5 and 1.0 microgram TRH) in sites adjacent to the PVN. The gastric force index was also significantly elevated from 61 to 120 min postinjection in rats receiving bilateral PVN microinjections of TRH (0.5 and 1.0 microgram). Peak gastric responses occurred within 10-20 min postinjection and represented an approximately eight-fold increase over basal values. In the remaining groups, the force index was not significantly altered from preinjection values. The excitatory action of TRH (1.0 microgram) on gastric contractility was completely abolished by subdiaphragmatic vagotomy. These results suggest that TRH acts within the PVN to stimulate gastric contractility via vagal-dependent pathways.

Animals↗

Raphe pallidus stimulation increases gastric contractility via TRH projections to the dorsal vagal complex in rats.

The role of thyrotropin releasing hormone (TRH) in the dorsal vagal complex (DVC) in mediating the enhanced gastric contractility induced by glutamate (100 pmol) microinjected into the raphe pallidus (Rpa) was investigated in urethane-anesthetized rats acutely implanted with miniature strain gauge force transducers on the corpus of the stomach. Glutamate-induced stimulation of gastric contractility was dose-dependently inhibited by bilateral microinjection into the DVC of TRH antibody (0.17, 0.85 or 1.7 micrograms/100 nl/site) but not by vehicle. TRH antibody microinjected into the dorsal medullary reticular field had no effect. These data indicate that activation of Rpa neurons by glutamate increases gastric motor function through TRH release in the DVC.

Animals↗

Myth of substituted judgment. Surrogate decision making regarding life support is unreliable.

OBJECTIVE: To identify factors predicting the accuracy of surrogate decision making in life support decisions. DESIGN: Questionnaire. SETTING: Urban Veterans Affairs hospital. PATIENTS AND DESIGN: Fifty hospitalized patients and their chosen surrogates were given questionnaires describing life support modalities and four common medical scenarios in which life support would be contemplated. An additional 50 patients also completed the questionnaire. Patients gave their choices of life support in the different scenarios. Surrogates guessed the patients' answers (substituted judgment). Details of the patient-surrogate relationship were asked. Patients completed a depression inventory. MAIN RESULTS: Surrogates correctly guessed patients' wishes about life support overall on 59.3% of the questions, not better than random chance (kappa = .09). The only predictor of accurate surrogate decision making was specific discussion between patient and surrogate about life support. SECONDARY RESULTS: Patients had an overall low desire for life support (35%), and a majority favored euthanasia under some circumstances (62%). There was no relationship between depression score and desire for life support. CONCLUSIONS: Substituted judgment by surrogates is not more accurate than random chance. Discussion between patient and surrogate about life support correlated with more accurate substituted judgment.

Adult↗

Effects of preadaptation to restricted feeding and cimetidine treatment on gastric mucosal injury and wheel running during exposure to activity-stress.

The relationship between gastric injury and wheel running was examined during an activity-stress (A-S) experiment. In Experiment 1, rats were preadapted to a 1-h restricted feeding schedule for either 0, 15, 25 or 35 days prior to entering activity wheels. All rats preadapted to the 1-h feeding schedule had significantly less gastric damage than rats without any preadaptation experience. Survival of A-S was related to the length of preadaptation experience. Regardless of preadaptation experience, rats increased daily running with the greatest increase occurring during the 6-h period preceding the feeding hour. In Experiment 2, rats were injected twice daily with cimetidine (100 mg, ip) or vehicle during the 6-h preceding the feeding session. Rats treated with cimetidine had less mucosal injury but had no increased survival when compared to rats injected with the vehicle. Cimetidine treated rats had essentially the same running pattern as controls. These results demonstrated that the process of mucosal injury did not stimulate excessive wheel running. The data also suggest that mucosal injury is not related to survival in A-S rats.

Adaptation, Physiological↗

Lateral hypothalamic lesions cause gastric injury by stimulating gastric contractility.

Changes in gastric contractility following lateral hypothalamic (LH) lesions with and without bilateral cervical vagotomy were measured in urethan-anesthetized rats. LH lesions were induced with direct current passed through stereotaxically placed electrodes. Gastric contractility was recorded continuously for 4 h with acutely implanted strain gauge force transducers and analyzed by computer. LH lesions consistently stimulated gastric contractility and caused more gastric mucosal injury than control conditions. Vagotomy blocked both gastric mucosal injury and high-amplitude gastric contractions. In rats with LH lesions and exogenously infused intragastric hydrochloric acid, atropine methyl nitrate inhibited high-amplitude gastric contractions and gastric erosions. These findings indicate that LH lesions stimulate vagally mediated high-amplitude gastric contractions, which, in the presence of hydrochloric acid, cause gastric mucosal erosions.

Animals↗

Thyrotropin-releasing hormone analog injected into the raphe pallidus and obscurus increases gastric contractility in rats.

The present study was performed to investigate the influence of the chemical stimulation of medullary raphe nuclei by the stable TRH (thyrotropin-releasing hormone) analog, RX 77368, on gastric contractility. Urethane-anesthetized rats were acutely implanted with miniature strain gauge force transducers on the corpus of the stomach for continuous recording of gastric contractility. Traces were analyzed by computer. Microinjections of vehicle or RX 77368 into the raphe pallidus or raphe obscurus were performed using pressure injection of 50 nl through glass micropipettes 30 min following basal recording of gastric contractility. RX 77368 (0.7-77 pmol) dose dependently stimulated gastric contractility when microinjected into the raphe pallidus and raphe obscurus. The stimulation of gastric contractions induced by microinjection of RX 77368 (77 pmol) into these raphe nuclei was completely blocked by vagotomy and prevented (raphe obscurus) or reduced (raphe pallidus) by atropine. RX 77368 (7.7-77 pmol) microinjected into the inferior olive, pyramidal tract, medial lemiscus was ineffective. These results demonstrate that chemical stimulation of the raphe pallidus and obscurus by RX 77368 stimulates gastric contractility through vagal and muscarinic pathways. These data suggest a role for medullary raphe nuclei in the central vagal regulation of gastric contractility.

Animals↗

CRF microinjected into the dorsal vagal complex inhibits TRH analog- and kainic acid-stimulated gastric contractility in rats.

The effect of CRF microinjected into the dorsal vagal complex (DVC) on centrally-stimulated gastric contractility was investigated in fasted, urethane-anesthetized rats. Miniature strain gauge force transducers were acutely implanted on the corpus of the stomach and contractility was analyzed by computer. Microinjection of the stable thyrotropin-releasing hormone (TRH) analog, RX 77368, (26 pmol) into the DVC induced a 12.2-fold stimulation of gastric contractility within 30 min. Corticotropin-releasing factor (CRF) (63-210 pmol) microinjected into the DVC concomitantly with RX 77368 (26 pmol) induced a dose-related inhibition of stimulated gastric contractility. Neither CRF alone (210 pmol) nor vehicle modified basal gastric contractility. Microinjection of kainic acid (141 pmol) into the raphe pallidus nucleus induced a 3.6-fold stimulation of gastric contractility after 45 min. This stimulation was suppressed by bilateral microinjection of CRF (105 pmol/site) into the DVC. These results demonstrate that CRF acts in the DVC to inhibit centrally-stimulated gastric contractility and suggest that TRH and CRF may interact in the DVC to regulate gastric motor function.

Animals↗