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Biomedical subjects

P Burnett

Publications and source records attributed to P Burnett.

At least 19 recordsLinked to original sources

Evidence of heterosexual bridging among syphilis-positive men who have sex with men.

OBJECTIVE: To explore whether heterosexual bridging among syphilis-positive men who have sex with men (MSM) contributes to increased infection rates among adolescent women in Baltimore City, Maryland. METHODS: Interview data for patients with primary, secondary and early-latent syphilis from January 2001 to July 2005 were linked with their corresponding field records for named exposed contacts to assess prevalence of male bisexual activity and risk profiles of potential male bisexual bridgers and their female sex partners. RESULTS: None of the women with syphilis reported having known heterosexual relationships with a bisexual man. However, 3.9% and 11.0% of the male sex partners of adolescent females and women aged >25 years with syphilis, respectively, self-reported as MSM or named male sex partners. Likewise, 10.3% of syphilis-positive MSM named female sex partners and 3.0% of syphilis-positive men who did not self-identify as MSM named both male and female sex partners. CONCLUSIONS: Sexual network links exist between syphilis-positive MSM and heterosexual women, but the extent of bisexual behaviour among men is not detectable by self-identification and disclosure to female sex partners.

Adolescent↗

Factors associated with the wish to hasten death: a study of patients with terminal illness.

BACKGROUND: There is considerable debate regarding the clinical issues surrounding the wish to hasten death (WTHD) in the terminally ill. The clinical factors contributing to the WTHD need further investigation among the terminally ill in order to enhance understanding of the clinical assessment and treatment needs that underlie this problem. A more detailed understanding may assist with the development of appropriate therapeutic interventions. METHOD: A sample of terminally ill cancer patients (N = 256) recruited from an in-patient hospice unit, home palliative care service and a general hospital palliative care consulting service from Brisbane Australia between 1998-2001 completed a questionnaire assessing psychological (depression and anxiety), social (family relationship, social support, level of burden on others) and the impact of physical symptoms. The association between these factors and the WTHD was investigated. RESULTS: A high WTHD was reported by 14 % of patients. A discriminant function analysis revealed that the following variables were associated with a high WTHD (P < 0.001): higher levels of depressive symptoms, being admitted to an in-patient hospice setting, a greater perception of being a burden on others, lower family cohesion, lower levels of social support, higher levels of anxiety and greater impact of physical symptoms. CONCLUSIONS: Psychological and social factors are related to a WTHD among terminally ill cancer patients. Greater attention needs to be paid to the assessment of psychological and social issues in order to provide appropriate therapeutic interventions for terminally ill patients.

Adult↗

Terminally ill cancer patients' wish to hasten death.

This exploratory study investigated factors associated with the wish to hasten death among a sample of terminally ill cancer patients. Semi-structured interviews conducted on a total of 72 hospice and home palliative care patients were subjected to qualitative analysis using QSR-NUDIST. The main themes to emerge suggested that patients with a high wish to hasten death had greater concerns with physical symptoms and psychological suffering, perceived themselves to be more of a burden to others, and experienced higher levels of demoralization, while also reporting less confidence in symptom control, fewer social supports, less satisfaction with life experiences and fewer religious beliefs when compared with patients who had a moderate or no wish to hasten death. The implications of these findings will be discussed.

Adult↗

Cyclosporin A inhibits inositol 1,4,5-trisphosphate-dependent Ca2+ signals by enhancing Ca2+ uptake into the endoplasmic reticulum and mitochondria.

Cytosolic Ca(2+) ([Ca(2+)](i)) oscillations may be generated by the inositol 1,4,5-trisphosphate receptor (IP(3)R) driven through cycles of activation/inactivation by local Ca(2+) feedback. Consequently, modulation of the local Ca(2+) gradients influences IP(3)R excitability as well as the duration and amplitude of the [Ca(2+)](i) oscillations. In the present work, we demonstrate that the immunosuppressant cyclosporin A (CSA) reduces the frequency of IP(3)-dependent [Ca(2+)](i) oscillations in intact hepatocytes, apparently by altering the local Ca(2+) gradients. Permeabilized cell experiments demonstrated that CSA lowers the apparent IP(3) sensitivity for Ca(2+) release from intracellular stores. These effects on IP(3)-dependent [Ca(2+)](i) signals could not be attributed to changes in calcineurin activity, altered ryanodine receptor function, or impaired Ca(2+) fluxes across the plasma membrane. However, CSA enhanced the removal of cytosolic Ca(2+) by sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA), lowering basal and inter-spike [Ca(2+)](i). In addition, CSA stimulated a stable rise in the mitochondrial membrane potential (DeltaPsi(m)), presumably by inhibiting the mitochondrial permeability transition pore, and this was associated with increased Ca(2+) uptake and retention by the mitochondria during a rise in [Ca(2+)](i). We suggest that CSA suppresses local Ca(2+) feedback by enhancing mitochondrial and endoplasmic reticulum Ca(2+) uptake, these actions of CSA underlie the lower IP(3) sensitivity found in permeabilized cells and the impaired IP(3)-dependent [Ca(2+)](i) signals in intact cells. Thus, CSA binding proteins (cyclophilins) appear to fine tune agonist-induced [Ca(2+)](i) signals, which, in turn, may adjust the output of downstream Ca(2+)-sensitive pathways.

Animals↗

Measuring psychological adjustment to HIV infection.

AIMS: A modified version of the Mental Adjustment to Cancer Scale (The Mental Adjustment to HIV Scale--MAHIVS) was used to evaluate patterns of psychological adjustment in response to HIV infection. METHODS: A sample of 164 HIV positive homosexual/bisexual men were recruited across three Australian centers (79 asymptomatic (CDC II/III) and 85 symptomatic HIV infection (CDC IV)). Factor analysis of the MAHIVS was conducted and the predictive validity of the MAHIVS was investigated using the General Health Questionnaire, while The Diagnostic Interview Schedule was used to assess current and lifetime psychiatric disorder. Other measures of adjustment/coping were used to investigate the construct validity of the MAHIVS (neuroticism, locus of control, defense style). RESULTS: Factor analysis of the MAHIVS detected four factors: Hopelessness, Fighting Spirit/Self Efficacy, Personal Control, and Minimization. Hopelessness and Fighting Spirit factors exhibited acceptable levels of internal consistency and validity, with significant correlations detected with psychological symptoms and significant association with other measures of psychological adjustment and personality. Fighting Spirit emerged as a potential indicator of psychological resilience, whereas Hopelessness was significantly associated with psychological symptoms and current major depression (but not past depression). CONCLUSIONS: The findings indicate the validity of the MAHIVS and support the presence of common themes in the psychological adaptation to life-threatening illness that can be detected across disease categories and groups.

Adaptation, Psychological↗

The glyoxylate cycle: does it function in the dormant or active bear?

The presence of or induction of an active glyoxylate cycle (GC) in the dormant black bear whose sole source of energy is body fat is an attractive concept which would allow lipid (acetate) to be directed from oxidation via the tricarboxylic acid cycle to many biosynthetic pathways. However, in spite of earlier claims, the present report establishes that isocitrate lyase and malate synthetase, GC marker enzymes, could not be detected in liver or kidney of active or dormant bears; liver peroxisome numbers were similar. The absence of brown fat (by light microscopy) and of the GC enzymes in the dormant bear raises questions about the prior report.

Animals↗

Integrating cytosolic calcium signals into mitochondrial metabolic responses.

Stimulation of hepatocytes with vasopressin evokes increases in cytosolic free Ca2+ ([Ca2+]c) that are relayed into the mitochondria, where the resulting mitochondrial Ca2+ ([Ca2+]m) increase regulates intramitochondrial Ca2+-sensitive targets. To understand how mitochondria integrate the [Ca2+]c signals into a final metabolic response, we stimulated hepatocytes with high vasopressin doses that generate a sustained increase in [Ca2+]c. This elicited a synchronous, single spike of [Ca2+]m and consequent NAD(P)H formation, which could be related to changes in the activity state of pyruvate dehydrogenase (PDH) measured in parallel. The vasopressin-induced [Ca2+]m spike evoked a transient increase in NAD(P)H that persisted longer than the [Ca2+]m increase. In contrast, PDH activity increased biphasically, with an initial rapid phase accompanying the rise in [Ca2+]m, followed by a sustained secondary activation phase associated with a decline in cellular ATP. The decline of NAD(P)H in the face of elevated PDH activity occurred as a result of respiratory chain activation, which was also manifest in a calcium-dependent increase in the membrane potential and pH gradient components of the proton motive force (PMF). This is the first direct demonstration that Ca2+-mobilizing hormones increase the PMF in intact cells. Thus, Ca2+ plays an important role in signal transduction from cytosol to mitochondria, with a single [Ca2+]m spike evoking a complex series of changes to activate mitochondrial oxidative metabolism.

Adenosine Triphosphate↗

Coupling between cytosolic and mitochondrial calcium oscillations: role in the regulation of hepatic metabolism.

Mitochondria are strategically localized at sites of Ca2+ release, such that increases in cytosolic free Ca2+ ([Ca2+]c) from either internal Ca2+ stores or Ca2+ influx across the plasma membrane can be rapidly transported into the mitochondrial matrix. The consequent elevation in mitochondrial Ca2+ ([Ca2+]m) stimulates the Ca2+-sensitive intramitochondrial dehydrogenases, resulting in elevation of NAD(P)H. The preferential coupling between increases in [Ca2+]c and [Ca2+]m is one proposed mechanism to coordinate mitochondrial ATP production with cellular energy demand. In liver cells, hormones that act through the second messenger inositol 1,4, 5-trisphosphate (IP3) generate oscillatory [Ca2+]c signals, which result from a periodic Ca2+- and IP3-mediated activation/deactivation of intracellular Ca2+ release channels. The [Ca2+]c spiking frequency increases with agonist dose, whereas the amplitude of each [Ca2+]c spike is constant. This frequency modulation of [Ca2+]c spiking encodes the signal from the extracellular agonist, which is then decoded by the internal Ca2+-sensitive proteins such as the Ca2+-sensitive intramitochondrial dehydrogenases. Our studies have investigated the relationship between IP3-dependent [Ca2+]c signals and [Ca2+]m in primary cultured hepatocytes. In addition, the changes in cellular [Ca2+] levels have been correlated with the regulation of intramitochondrial NAD(P)H levels, pyruvate dehydrogenase activity and the magnitude of the mitochondrial proton motive force.

Aequorin↗

Posttraumatic stress disorder in response to HIV infection.

This study investigated the psychological impact of HIV infection through assessment of posttraumatic stress disorder in response to HIV infection. Sixty-one HIV-positive homosexual/bisexual men were assessed for posttraumatic stress disorder in response to HIV infection (PTSD-HIV) using a modified PTSD module of the DIS-III-R. Thirty percent met criteria for a syndrome of posttraumatic stress disorder in response to HIV diagnosis (PTSD-HIV). In over one-third of the PTSD cases, the disorder had an onset greater than 6 months after initial HIV infection diagnosis. PTSD-HIV was associated with other psychiatric diagnoses, particularly the development of first episodes of major depression after HIV infection diagnosis. PTSD-HIV was significantly associated with a pre-HIV history of PTSD from other causes, and other pre-HIV psychiatric disorders and neuroticism scores, indicating a similarity with findings in studies of PTSD from other causes. The findings from this preliminary study suggest that a PTSD response to HIV diagnosis has clinical validity and requires further investigation in this population and other medically ill groups. The results support the inclusion of the diagnosis of life-threatening illness as a traumatic incident that may lead to a posttraumatic stress disorder, which is consistent with the DSM-IV criteria.

Adult↗

A longitudinal study comparing bereavement phenomena in recently bereaved spouses, adult children and parents.

OBJECTIVE: The study investigated previous research findings and clinical impressions which indicated that the intensity of grief for parents who had lost a child was likely to be higher than that for widows/widowers, who in turn were likely to have more intense reactions than adult children losing a parent. METHOD: In order to compare the intensities of the bereavement reactions among representative community samples of bereaved spouses (n = 44), adult children (n = 40) and parents (n = 36), and to follow the course of such phenomena, a detailed Bereavement Questionnaire was administered at four time points over a 13-month period following the loss. RESULTS: Measures based on items central to the construct of bereavement showed significant time and group differences in accordance with the proposed hypothesis. More global items associated with the construct of resolution showed a significant time effect, but without significant group differences. CONCLUSIONS: Evidence from this study supports the hypothesis that in non-clinical, community-based populations the frequency with which core bereavement phenomena are experienced is in the order: bereaved parents > bereaved spouses > bereaved adult children.

Adaptation, Psychological↗

Measuring core bereavement phenomena.

As part of a longitudinal study of bereavement phenomena in three groups, bereaved spouses, bereaved adult children and bereaved parents, scale development was carried out using a pool of bereavement phenomenology questions administered prospectively. The items were derived from the literature, in particular studies dealing with the measurement of grief/bereavement, as well as from clinical experience. Factor analysis of theoretically grouped items produced seven subscales, three of which tapped frequently experienced phenomena in the bereaved. These three subscales formed the basis of a single measure, labelled the Core Bereavement Items (CBI), which demonstrated high reliability and sound face and discriminant validity. Preliminary analysis suggested that the CBI will prove to be a reliable and valid instrument with respect to the measure of core bereavement phenomena in commonly bereaved groups in Western society.

Adult↗

Psychological distress and bereavement.

Some 115 bereaved subjects (43 spouses, 39 adult children, and 33 parents) were followed-up prospectively over 12 months following the acute bereavement period. They completed the Zung Depression Scale, Spielberger's State and Trait Anxiety Measure, the GHQ-28, and Eysenck's Personality Inventory at four time points. With the exception of EPI-Extroversion, there was a significant decrease in all scores over the period encompassing the study. There were no differences between the three groups on any of the psychological variables measured. Scores on the Zung Depression Scale, state and trait anxiety, and neuroticism correlated significantly with a measure of core bereavement phenomenology, the Core Bereavement Items, at each time point for each group.

Adaptation, Psychological↗

Subcellular imaging of intramitochondrial Ca2+ with recombinant targeted aequorin: significance for the regulation of pyruvate dehydrogenase activity.

Specific targeting of the recombinant, Ca2+ -sensitive photoprotein, aequorin to intracellular organelles has provided new insights into the mechanisms of intracellular Ca2+ homeostasis. When applied to small mammalian cells, a major limitation of this technique has been the need to average the signal over a large number of cells. This prevents the identification of inter- or intracellular heterogeneities. Here we describe the imaging in single mammalian cells (CHO.T) of [Ca2+] with recombinant chimeric aequorin targeted to mitochondria. This was achieved by optimizing expression of the protein through intranuclear injection of cDNA and through the use of a charge-coupled device camera fitted with a dual microchannel plate intensifier. This approach allows accurate quantitation of the kinetics and extent of the large changes in mitochondrial matrix [Ca2+] ([Ca2+](m)) that follow receptor stimulation and reveal different behaviors of mitochondrial populations within individual cells. The technique is compared with measurements of [Ca2+](m) using the fluorescent indicator, rhod2. Comparison of [Ca2+](m) with the activity of the Ca2+ -sensitive matrix enzyme, pyruvate dehydrogenase (PDH), reveals that this enzyme is a target of the matrix [Ca2+] changes. Peak [Ca2+](m) values following receptor stimulation are in excess of those necessary for full activation of PDH in situ, but may be necessary for the activation of other mitochondrial dehydrogenases. Finally, the data suggest that the complex regulation of PDH activity by a phosphorylation-dephosphorylation cycle may provide a means by which changes in the frequency of cytosolic (and hence mitochondrial) [Ca2+] oscillations can be decoded by mitochondria.

Aequorin↗

The hormonal regulation of pyruvate dehydrogenase complex.

The pyruvate dehydrogenase complex has a central role in the regulation of mammalian metabolism as it represents the point-of-no-return in the utilization of carbohydrate. This article summarizes our studies into how signalling systems initiated by hormones binding to cell surface receptors can reach the pyruvate dehydrogenase system which is located within the inner mitochondrial membrane. One class of hormones which activate pyruvate dehydrogenase are those that increase cytoplasmic Ca2+. A wide range of studies on isolated enzymes, separated mitochondria and intact cell preparations have shown that the activation is due to the stimulation of pyruvate dehydrogenase phosphatase. Two other intramitochondrial dehydrogenases which regulate the citrate acid cycle are activated in parallel and this is an important means of balancing the supply of ATP to increasing cell demand. Insulin is also able to activate pyruvate dehydrogenase, but this is restricted to fat and other cells capable of lipogenesis. Insulin acts by stimulating pyruvate dehydrogenase phosphatase, but the activation does not involve alterations in Ca2+. The signalling pathway involved has not been established, but it appears to be quite distinct from those involved in many other actions of insulin.

Acetyl-CoA Carboxylase↗

The bereavement response: a cluster analysis.

BACKGROUND: Literature and clinical experience suggest that some people experience atypical, complicated or pathological bereavement reactions in response to a major loss. METHOD: Three groups of community-based bereaved subjects--spouses (n = 44), adult children (n = 40), and parents (n = 36)--were followed up four times in the 13 months after a loss. A 17-item scale of core bereavement times was developed and used to investigate the intensity of the bereavement response over time. RESULTS: Cluster analysis revealed a pattern of bereavement-related symptoms approximating a syndrome of chronic grief in 11 (9.2%) of the 120 subjects. None of the respondents displayed a pattern consistent with delayed or absent grief. CONCLUSIONS: In a non-clinical community sample of bereaved people, delayed or absent grief is infrequently seen, unlike chronic grief, which is demonstrated in a minority.

Adult↗

The development of a clinical learning environment scale.

Within nursing, there is a strong demand for high-quality, cost-effective clinical education experiences that facilitate student learning in the clinical setting. The clinical learning environment (CLE) is the interactive network of forces within the clinical setting that influence the students' clinical learning outcomes. The identification of factors that characterize CLE could lead to strategies that foster the factors most predictive of desirable student learning outcomes and ameliorate those which may have a negative impact on student outcomes. The CLE scale is a 23-item instrument with five subscales: staff-student relationships, nurse manager commitment, patient relationships, interpersonal relationships, and student satisfaction. These factors have strong substantive face validity and construct validity, as determined by confirmatory factor analysis. Reliability coefficients range from high (0.85) to marginal (0.63). The CLE scale provides the educator with a valid and reliable instrument to evaluate affectively relevant factors in the CLE, direct resources to areas where improvement may be required, and nurture those areas functioning well. It will assist in the application of resources in a cost-effective, efficient, productive manner, and will ensure that the clinical learning experience offers the nursing student the best possible learning outcomes.

Adolescent↗

Concepts of normal bereavement.

This study used a 25-item questionnaire to examine the perceptions of 128 people with a close interest in bereavement and its literature. The study is part of a project to identify key aspects and the bereavement process. Subjects were asked to rate their perceptions of key bereavement phenomena with regards their frequency in the acute and later stages of bereavement. Descriptive results are presented and discussed, and a profile of phenomena perceived to be common to both stages is outlined.

Adaptation, Psychological↗