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Biomedical subjects

G E Hunt

Publications and source records attributed to G E Hunt.

At least 19 recordsLinked to original sources

The development and evaluation of a measure to assess cancer survivors' unmet supportive care needs: the CaSUN (Cancer Survivors' Unmet Needs measure).

BACKGROUND: Many cancer survivors experience ongoing morbidity over the survivorship continuum and their supportive care needs have yet to be comprehensively assessed. METHODS: This study aimed to develop and empirically evaluate a self-report measure of cancer survivors' supportive care needs. In Phase I, questionnaire items were generated based upon previous qualitative research that identified both unique and shared needs in survivors and their partners; items were constructed into the Cancer Survivors' Unmet Needs measure (CaSUN). In Phase 2, the CaSUN was completed by 353 cancer survivors who had been diagnosed with cancer between 1 and 15 years earlier and were currently disease-free. RESULTS: After modification, the CaSUN included 35 unmet need items, 6 positive change items and an open-ended question. Good acceptability, internal consistency and validity were demonstrated, although test-retest reliability was low. Maximum likelihood factor analysis identified five discrete factors: Existential Survivorship, Comprehensive Care, Information, Quality of Life and Relationships. CONCLUSIONS: Preliminary data indicates that the CaSUN meets the majority of psychometric criteria for assessment measures, although its low test-retest reliability awaits further investigation. The CaSUN will facilitate the evaluation of supportive care services and generation of service delivery recommendations for cancer survivors.

Adult↗

Assessing unmet supportive care needs in partners of cancer survivors: the development and evaluation of the Cancer Survivors' Partners Unmet Needs measure (CaSPUN).

BACKGROUND: Partners of cancer patients typically provide the majority of patients' emotional and physical care. Partners may be profoundly affected by the cancer and may experience ongoing supportive care needs across the survivorship continuum. Research has been restricted by a lack of psychometrically evaluated measures and in this study, a self-report measure of partners' needs was developed and empirically evaluated. METHODS: Questionnaire items generated from a qualitative study were constructed into a 47- item unmet need measure (Cancer Survivors' Partners Unmet Needs measure, CaSPUN). The psychometric properties of the CaSPUN were evaluated in 212 partners of patients who had been diagnosed with cancer 1-11 years earlier and were currently disease-free. RESULTS: The CaSPUN was modified to include 35 unmet need items, 6 positive change items and an open ended item. The CaSPUN demonstrates a high level of acceptability, internal consistency and construct validity, although test-retest reliability was moderate. Factor analysis identified five discrete factors: (1) Relationships, (2) Information, (3) Partner Issues, (4) Comprehensive Care and (5) Emotional Support. CONCLUSIONS: The CaSPUN permits the identification of long-term supportive care needs in generic populations of cancer survivors' partners and will assist with the formulation of recommendations regarding required supportive care services.

Adult↗

Life after cancer: couples' and partners' psychological adjustment and supportive care needs.

GOALS OF WORK: Partners of cancer patients may experience significant distress at the time of treatment and many may experience persistent difficulties, although little research has examined their longer term psychosocial outcomes or supportive care needs. MATERIALS AND METHODS: One hundred and fifty-four cancer survivors who were 1-11 years post diagnosis and disease-free and their partners completed mailed questionnaires. MAIN RESULTS: A positive relationship was found between psychological distress and supportive care needs both within and between partner and survivor samples. Partners reported high levels of anxiety and supportive care needs, most frequently concerning relationships and the impact of the cancer illness. Partners within couples reported both shared and unique needs, although agreement on ratings of shared needs was low. Needs did not diminish over time although partners demonstrated psychological resilience and reported positive outcomes. Predictors of distress and unmet needs were explored: physical QOL, relationship satisfaction, and total needs contributed to variability in partners' distress; relationship satisfaction and total needs were associated with survivors' distress. Distress and relationship satisfaction were associated with partners' unmet needs; only distress was associated with survivors' unmet needs. CONCLUSIONS: Partners are not merely providers of support, but need support themselves many years after a cancer diagnosis and in the context of apparently cured disease. The quality of the dyadic relationship may be critical in determining both partner and survivor distress and needs, and may prove a useful target for psychosocial interventions.

Adaptation, Psychological↗

The patient's view of need and caregiving consequences: a cross-sectional study of inpatients with severe mental illness.

This cross-sectional study was conducted across inpatient facilities of a metropolitan mental health service in Sydney, Australia. Given shorter lengths of stay in acute inpatient facilities, it is important to ascertain differences between patients' and carers' perceptions of need and support in order to guide delivery of care in the community. The objectives were to: (1) assess the needs of patients recently admitted to hospital and ascertain the level of carer involvement while in hospital; (2) compare the degree of agreement between patients' and carers' perceptions of need and caregiver burden; and (3) determine the relationship between levels of need and carer burden prior to hospitalization. Over a 2-month period, consecutive patients (n = 200) were interviewed using the Camberwell Assessment of Need Short Appraisal Schedule and a modified version of the Involvement Evaluation Questionnaire to assess basic needs and patient perceptions of caregiver burden, respectively. Of the 200 patients interviewed, 68% (n = 135) identified a carer. Patients with schizophrenia had most met needs, those with affective disorders had most unmet needs and patients with other diagnoses recorded the lowest number of needs overall. The level of agreement between patient and carer perceptions of need was low, possibly because of confusion about the definition of need or different views about the support required to fulfil a need. Patients underestimated the consequences of caregiving, especially the impact of strained atmosphere, global burden, worrying about their future and encouragement to undertake an activity, indicating that carers were more burdened than patients perceived them to be.

Activities of Daily Living↗

Regional differences in naloxone modulation of Delta(9)-THC induced Fos expression in rat brain.

Recent behavioral and pharmacological research shows extensive interplay between cannabinoid and opioid neurochemical systems. Here we examined the neuroanatomical basis of this interaction using c-fos immunohistochemistry. We compared Fos immunoreactivity in groups of male albino Wistar rats treated with vehicle, Delta(9)-tetrahydrocannabinol (THC, 10 mg/kg, i.p.), naloxone (10 mg/kg, i.p.) or THC and naloxone in combination. Locomotor activity was depressed in both THC treatment groups and moderately inhibited in rats given naloxone alone. Results showed that naloxone inhibited THC-induced Fos immunoreactivity in several key brain regions including the ventral tegmental area, ventromedial and dorsomedial hypothalamus, central caudate-putamen and ventrolateral periaqueductal grey. Conversely, naloxone and THC had an additive effect on Fos immunoreactivity in the central nucleus of the amygdala, the bed nucleus of the stria terminalis (lateral division), the insular cortex, and the paraventricular nucleus of the thalamus. These findings complement earlier pharmacological results showing potent modulation of cannabinoid-induced analgesia, appetite and reward by opioids. The inhibitory effects of naloxone on THC-induced ventral tegmentum, hypothalamic and periaqueductal grey Fos expression point to these structures as key sites involved in cannabinoid-opioid interactions.

Animals↗

Age, period and cohort effects on suicide rates in Australia, 1919-1999.

OBJECTIVE: To examine age, period and cohort effects on Australian suicide rates. METHOD: Male suicide rates for successive 5-year periods between 1919 and 1998, and for 1999 were displayed graphically to examine interactions between age, period and cohort effects. RESULTS: There has been a pronounced period effect on male suicide rates in all age groups over the last few decades, with lower rates in wartime and peak rates for most cohorts in the 1960s. Peak rates of all adult female 5-year age cohorts occurred in the 1960s or early 1970s. CONCLUSION: Most so-called cohort effects appear to be associated with environmental changes that may not be a function of the cohort itself. While much attention has focused on the rising suicide rates in young males in Australia, local media and health authorities have given little emphasis to the high rates found in elderly males.

Adolescent↗

Increased anxiety and impaired memory in rats 3 months after administration of 3,4-methylenedioxymethamphetamine ("ecstasy").

Male Wistar rats were administered either (a) a high dose regime of 3,4-methylenedioxymethamphetamine (MDMA) (4 x 5 mg/kg, i.p. over 4 h on each of 2 consecutive days), (b) a moderate dose regime of MDMA (1 x 5 mg/kg on each of 2 consecutive days), (c) D-amphetamine (4 x 1 mg/kg over 4 h on each of 2 days), or (d) vehicle injections. The high MDMA dose regime and the amphetamine treatment both produced acute hyperactivity and hyperthermia. Twelve weeks later, all rats were tested in the drug-free state on a battery of anxiety tests (elevated plus maze, emergence and social interaction tests). A further 2 weeks later they were tested on a novel object recognition memory task. Rats previously given the neurotoxic dose of MDMA showed greater anxiety-like behaviour on all three anxiety tests relative to both controls and D-amphetamine-treated rats. Rats given the moderate MDMA dose regime also showed increased anxiety-like behaviour on all three tests, although to a lesser extent than rats in the high dose group. In the object recognition task, rats given the high MDMA dose regime showed impaired memory relative to all other groups when tested at a 15-min delay but not at a 60-min delay. Rats previously exposed to amphetamine did not differ from saline controls in the anxiety or memory tests. These data suggest that moderate to heavy MDMA exposure over 48 h may lead to increased anxiety and memory impairment 3 months later, possibly through a neurotoxic effect on brain serotonin systems.

Animals↗

The distribution of cannabinoid-induced Fos expression in rat brain: differences between the Lewis and Wistar strain.

Previous studies have suggested that cannabis-like drugs produce mainly aversive and anxiogenic effects in Wistar strain rats, but rewarding effects in Lewis strain rats. In the present study we compared Fos expression, body temperature effects and behavioral effects elicited by the cannabinoid CB(1) receptor agonist CP 55,940 in Lewis and Wistar rats. Both a moderate (50 microg/kg) and a high (250 microg/kg) dose level were used. The 250 microg/kg dose caused locomotor suppression, hypothermia and catalepsy in both strains, but with a significantly greater effect in Wistar rats. The 50 microg/kg dose provoked moderate hypothermia and locomotor suppression but in Wistar rats only. CP 55,940 caused significant Fos immunoreactivity in 24 out of 33 brain regions examined. The most dense expression was seen in the paraventricular nucleus of the hypothalamus, the islands of Calleja, the lateral septum (ventral), the central nucleus of the amygdala, the bed nucleus of the stria terminalis (lateral division) and the ventrolateral periaqueductal gray. Despite having a similar distribution of CP 55,940-induced Fos expression, Lewis rats showed less overall Fos expression than Wistars in nearly every brain region counted. This held equally true for anxiety-related brain structures (e.g. central nucleus of the amygdala, periaqueductal gray and the paraventricular nucleus of the hypothalamus) and reward-related sites (nucleus accumbens and pedunculopontine tegmental nucleus). In a further experiment, Wistar rats and Lewis rats did not differ in the amount of Fos immunoreactivity produced by cocaine (15 mg/kg). These results indicate that Lewis rats are less sensitive to the behavioral, physiological and neural effects of cannabinoids. The exact mechanism underlying this subsensitivity requires further investigation.

Analgesics↗

Effects of the cannabinoid receptor agonist CP 55,940 and the cannabinoid receptor antagonist SR 141716 on intracranial self-stimulation in Lewis rats.

Lewis rats were trained to self-stimulate the medial forebrain bundle (MFB) using a rate-frequency paradigm. They were then tested for the effects of the cannabinoid receptor agonist CP 55,940, the selective cannabinoid receptor antagonist SR 141716 and the dopamine D1 receptor antagonist SCH 23390. CP 55,940 (0, 10, 25 and 50 microg/kg i.p.) had no effect on MFB self-stimulation behaviour as assessed by the M50, the stimulation frequency at which half-maximal response rates were obtained. With SR 141716, only a very high dose (20 mg/kg i.p.) caused a significant inhibition of the rewarding efficacy of the stimulation. This was seen as an increase in the M50. All other doses of SR 141716 (0, 1, 3, 10 mg/kg i.p.) were ineffective in modulating the M50. By comparison, a relatively low dose (0.06 mg/kg i.p.) of SCH 23390 caused a large increase in M50. These results indicate a relatively modest influence, if any at all, of exogenous or endogenous cannabinoids on reward-relevant neurotransmission.

Animals↗

"When a rat smells a cat": the distribution of Fos immunoreactivity in rat brain following exposure to a predatory odor.

Wistar rats were exposed to a fabric collar that had been worn by a domestic cat. Exposure took place in an open rectangular arena containing a small wooden "hide box". Rats exposed to cat odor spent more than 87% of their time in the hide box during a single 20-min exposure session, whereas rats exposed to a control odor (an unworn collar) spent less than 20% of their time hiding. One hour following this session, rats were killed and Fos immunoreactivity was compared between cat odor-exposed rats, control odor-exposed rats and an additional group that had remained in their home cages. Cat odor-exposed rats showed greater Fos expression than controls in many brain regions, particularly in the medial amygdala, medial hypothalamus and periaqueductal gray. Significant findings included strong and selective induction of Fos in the posteroventral medial amygdaloid nucleus, the premamillary nucleus (dorsal part), ventromedial hypothalamic nucleus (dorsomedial part), dorsomedial hypothalamic nucleus, periaqueductal gray (dorsomedial, dorsolateral and ventrolateral parts) and the cuneiform nucleus. Robust Fos expression in the ventromedial hypothalamus, premamillary nucleus and periaqueductal gray confirms previous suggestions of a role for these areas in predator-induced defensive behavior. Fos immunoreactivity in the medial, but not central or basolateral amygdala is a novel finding and draws attention to this subregion as a possible interface between olfactory input and emotional output.

Animals↗

The distribution of 3,4-methylenedioxymethamphetamine "Ecstasy"-induced c-fos expression in rat brain.

Rats were injected with 3,4-methylenedioxymethamphetamine ("Ecstasy") and assessed for changes in locomotor activity and for the expression of the immediate early gene c-fos throughout the brain. A dose-dependent increase in locomotor activity was seen with 3,4-methylenedioxymethamphetamine (0, 5 and 20 mg/kg) that continued for at least 2 h following administration. Dose-dependent increases in c-fos expression were seen in much of the cortex, forebrain, brainstem and cerebellum in rats given 3,4-methylenedioxymethamphetamine. Expression was pronounced in 5-hydroxytryptamine terminal regions including the medial prefrontal cortex, caudate-putamen, nucleus accumbens, olfactory tubercle, islands of Calleja, lateral septum, paraventricular hypothalamus and paraventricular thalamus. High levels of c-fos expression were also seen in the supraoptic and median preoptic nuclei, regions involved in the control of fluid balance and body temperature, respectively. This is potentially important since deaths in 3,4-methylenedioxymethamphetamine users have been linked to hyperthermia and hyponatremia. In the brainstem, two regions of high c-fos expression were Barrington's nucleus, which is involved in micturition, and the pontine reticular nucleus oralis, a region involved in motor control of mastication. Activation of this latter structure may partly explain the bruxism (grinding of the jaw) reported by human 3,4-methylenedioxymethamphetamine users. Robust c-fos expression was seen in the cerebellum, particularly in the flocculus, and this may explain the reported deleterious effects of 3,4-methylenedioxymethamphetamine on balance and co-ordination. Significant c-fos expression was also seen in the ventral tegmental area, amidst the cell bodies of mesolimbic and mesocortical dopamine neurons, and in the median and dorsal raphe, where the serotonergic innervation of the forebrain originates. Double-labelling of fos-positive neurons with 5-hydroxytryptamine showed that only a small number of serotonergic neurons in the raphe expressed c-fos following 3,4-methylenedioxymethamphetamine. The widespread distribution of 3,4-methylenedioxymethamphetamine-induced c-fos expression seen in this study can be linked to the profound alterations in physiological function, mood and behaviour produced by this drug.

Animals↗

Beer consumption in rats: the influence of ethanol content, food deprivation, and cocaine.

A series of experiments examined various aspects of beer consumption in male Wistar rats. In the first experiment, rats were given home cage access to either beer or ethanol solutions under free access conditions. It was found that rats consumed greater amounts of moderate strength beer (2.7% ethanol by volume) or regular strength beer (5.0% ethanol) than equivalent dilute ethanol solutions in water. Consumption of 2.7% beer was greater than 5.0% beer and access to either beer, but not dilute ethanol, solutions caused substantial increases in total fluid intake per day. In the second experiment, individual rats given daily 30-min drink sessions consumed more 2.7% beer than 3.85% beer and more 3.85% than 5.0% beer. A "hangover" effect was evident after the first day of consumption of 5.0% beer with subsequent intake of this beer suppressed after high intake on first exposure. Intake of the low-strength beer approached intake of isocaloric (8.6%) sucrose solution. In a third experiment, a lick-based progressive ratio paradigm was implemented where rats had to emit progressively greater number of licks for a fixed volume (0.1 ml) of 2.7% beer or 8.6% sucrose. Using this paradigm, it was shown that food deprivation increased the motivation to consume beer and sucrose as shown by elevated break points (the highest ratio reached). Food deprivation also increased locomotor activity in the drinking environment. In contrast, cocaine (20 but not 10 mg/kg) caused a decrease in the break point for sucrose and beer, an effect probably mediated by the anorexic properties of the drug. It is concluded that rats will avidly consume beer, particularly of moderate alcohol content, but that such consumption may be mediated more by the nutritive and palatable characteristics of the beer rather than by the psychoactive effects of the alcohol it contains.

Animals↗

A comparison of delta 9-THC and anandamide induced c-fos expression in the rat forebrain.

Rats were injected with the cannabinoid receptor agonists delta 9-THC (5 mg/kg) or anandamide (20 mg/kg) and assessed for changes in body temperature and locomotor activity. Their brains were then examined for the expression of the immediate early gene c-fos. Similar reductions in body temperature and locomotor activity were seen with delta 9-THC and anandamide although there was evidence, in line with previous reports, to suggest a shorter duration of action of anandamide. delta 9-THC and anandamide caused equally high levels of c-fos expression in the paraventricular nucleus of the hypothalamus and the lateral septum. Both drugs also increased c-fos expression in the central nucleus of the amygdala although the effect was greater with delta 9-THC. Only delta 9-THC caused significant increases in c-fos expression in the nucleus accumbens and caudate-putamen. These differences may be linked to differential activation of cannabinoid receptor subtypes or to differences in efficacy in activating second messenger systems linked to cannabinoid receptors. These findings complement evidence of qualitative differences in the actions of anandamide and delta 9-THC emerging from tests of drug discrimination, cross-tolerance, conditioned place preference and anxiety.

Animals↗

Possible neural substrates of beer-craving in rats.

Rats voluntarily consumed beer in a distinctive environment during 30 min daily sessions over 21 days, ingesting a daily average of 0.96 g/kg of ethanol. On a final test day, rats in a 'craving' condition were denied access to the beer in the drinking environment. The expression of c-fos in the brain of 'craving' rats was compared with that in rats given free access on the test day ('beer' condition), and to rats which had been repeatedly placed in the drinking environment without ever having access to beer ('control' condition). Rats in the 'craving' condition showed significantly higher c-fos counts than either the 'beer' or 'control' rats in a variety of corticolimbic and brainstem structures, indicating that activation of these regions occurs when a desirable alcoholic beverage is expected but not received.

Alcoholism↗

Effects of pre-exposure and co-administration of the cannabinoid receptor agonist CP 55,940 on behavioral sensitization to cocaine.

Rats given cocaine (15 mg/kg, i.p.) every second day over a 2-week period displayed a progressively greater locomotor response to the drug over days indicating behavioral sensitization. When the cannabinoid receptor agonist CP 55,940 ((-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hyd roxypropyl)cyclohexanol) (10, 25 or 50 microg/kg) was administered under a similar regime, no such sensitization was observed. Rather, the two highest doses of CP 55,940 (25 and 50 microg/kg) caused locomotor suppression that lasted throughout administration. When rats pre-exposed 10 times to CP 55,940 were challenged with cocaine (15 mg/kg), no exaggerated locomotor response to cocaine was evident relative to non pre-exposed rats. When these rats were subsequently re-tested with CP 55,940, the cannabinoid continued to produce a dose-dependent suppression of locomotor activity. Finally, when CP 55,940 (50 microg/kg) was co-administered with cocaine, it significantly reduced the locomotor hyperactivity produced by the drug but did not block the development of behavioral sensitization. These results show that CP 55,940 does not sensitize locomotor activity with repeated administration in the same way as cocaine, and that pre-exposure or concurrent exposure to CP 55,940 does not enhance sensitivity to the subsequent behavioral effects of cocaine.

Analgesics↗

Rewarding brain stimulation induces only sparse Fos-like immunoreactivity in dopaminergic neurons.

In this study, c-fos immunohistochemistry was used to identify the brain regions activated by rewarding brain stimulation in rats. Rats had monopolar electrodes implanted in the medial forebrain bundle and were allocated to either a self-stimulation (n = 4), yoked stimulation (n = 4) or no stimulation (n = 6) group. In a single 1 h test session, each rat in the self-stimulation group made 1000 nose poke responses with each response followed by a 0.5 s train of brain stimulation. Rats in the yoked-stimulation group were paired with a partner in the self-stimulation group and received brain stimulation whenever their partner did. However, their nose poke responses did not trigger stimulation. This yoked procedure was thus used to identify any Fos-like immunoreactivity due to operant responding. Rats in the no stimulation group were placed in the same apparatus as the other rats but received no brain stimulation and were thus used to assess baseline Fos-like immunoreactivity. Results showed that stimulation increased Fos-like immunoreactivity in many areas of the brain in both the self-stimulation and yoked groups. The areas with the highest Fos-like immunoreactivity were ipsilateral to the electrode site and included the medial prefrontal cortex, lateral septum, nucleus accumbens (shell), the medial and lateral preoptic areas, bed nucleus of the stria terminalis, central amygdala, lateral habenula, dorsomedial hypothalamus, lateral hypothalamus and the anterior ventral tegmental area. Bilateral Fos-like immunoreactivity was evident in the nucleus accumbens core, paraventricular nucleus of the hypothalamus, the retrorubral fields and the locus coeruleus. A double-labelling procedure identifying both Fos and tyrosine hydroxylase was used to show that very few (< 5%) of the A10 dopamine cell bodies in the ventral tegmental area expressed Fos following brain stimulation. In contrast, most of the noradrenergic neurons of the locus coeruleus (A6), rubrospinal tract (A5) and pontine tegmental area (A7) were Fos positive. Overall, the results show that rewarding, brain stimulation induces Fos-like immunoreactivity in many forebrain regions but only sparsely in mesolimbic and mesocortical dopamine neurons. The similar patterns of Fos-like immunoreactivity seen in the self-stimulation and yoked-stimulation groups suggests that the operant responding for brain stimulation causes minimal Fos expression in itself.

Animals↗

Nitric oxide and cyclic GMP attenuate sensitivity of the blood-tumor barrier permeability to bradykinin.

Intracarotid infusion of bradykinin and its analogue, RMP-7, selectively increase the permeability of brain tumor capillaries though the nitrix oxide (NO) and cyclic GMP pathway. Maximum blood-tumor barrier (BTB) permeability induced by bradykinin is observed at 15 min after intracarotid infusion and this effect is decreased even if the infusion continues. The mechanism for this decreased effect with long term infusion has not been clearly defined. This study sought to determine the involvement of the NO-cyclic GMP pathway in this event. Regional permeability was investigated in 44 Wistar rats with implanted RG2 gliomas, using quantitative autoradiography to determine the unidirectional transfer constant (Ki) of radiolabeled 14C-dextran. Tumor bearing rats were treated by intracarotid infusion of bradykinin (10 micrograms kg-1 min-1) with or without pretreatment with bradykinin, the NO donor s-nitrosoglutathione (10 nmol kg-1 min-1), or the cyclic GMP analogue, 8Br-cyclic GMP (200 micrograms kg-1 min-1). At 30 min of bradykinin infusion, BTB permeability was significantly lower compared to 15 min of bradykinin infusion (3.79 +/- 0.99 vs. 16.20 +/- 3.43 microliters g-1 min-1, p < 0.001). Pretreatment with an NO donor significantly decreased BTB permeability in bradykinin infused rats (5.09 +/- 2.61 vs. 13.51 +/- 4.19 microliters g-1 min-1, p < 0.001), as did pretreatment with a cyclic GMP analogue (4.48 +/- 0.95 vs. 12.31 +/- 3.90 microliters g-1 min-1, p < 0.001). There was no increased permeability in nontumor brain areas. Increased tumor permeability by bradykinin appears to be regulated by NO and cyclic GMP which are second messengers involved in the bradykinin B2 receptor mediated cascade.

Animals↗