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S M Dunn

Publications and source records attributed to S M Dunn.

At least 37 records · Page 2Linked to original sources
PubMed2001

Hearing the bad news of a cancer diagnosis: the Australian melanoma patient's perspective.

BACKGROUND: In the past, recommendations on how to break the bad news of a cancer diagnosis have been based on expert opinion. Recently, consensus-based guidelines for medical practitioners have been developed. The objective of this work is to investigate patient preferences for communication practices and to identify any disparities between these guidelines, patient preferences and patient recollections of hearing their diagnosis. PATIENTS AND METHODS: A consecutive sample of 131 newly diagnosed melanoma patients were surveyed approximately 4 months after initial diagnosis to document their preferences and recollections of their communication experiences. RESULTS: Of the 'breaking bad news' recommendations investigated, patients did not strongly endorse the doctor helping tell others of the diagnosis or telling the patient about cancer support services. Very few patients expressed a preference for having another health professional present. One communication feature, the patient feeling confident about getting the best treatment, was endorsed as 'very important' but does not feature in published guidelines. The most notable disparities between guidelines and the reported experiences of patients related to perceived delays in receiving the diagnosis, and having adequate opportunity to ask their clinician questions. CONCLUSION: Current Australian recommendations on how to communicate a diagnosis of cancer were generally supported by the patients' expressed preferences, but several modifications are proposed. IMPLICATIONS: Suggestions are offered to help overcome the disparities identified between recommendations and patients' preferences when a diagnosis of cancer is being communicated.

Adaptation, Psychological↗
PubMed2001

Mutagenesis of the GABA(A) receptor alpha1 subunit reveals a domain that affects sensitivity to GABA and benzodiazepine-site ligands.

We have mutated several amino acids in the region of the GABA(A) receptor alpha1 subunit predicted to form a small extracellular loop between transmembrane domains two and three to investigate its possible role in ligand sensitivity. The mutations were S275T, L276A, P277A, V279A, A280S and Y281F. Mutant alpha1 subunits were co-expressed with beta2 and gamma2 subunits in tsA201 cells or Xenopus oocytes. Binding studies revealed that the only mutation that significantly affected [3H]Ro15-4513 binding was the V279A substitution which reduced the affinity for this ligand. Electrophysiological examination of mutant receptors revealed that L276A, P277A and V279A displayed rightward shifts of their GABA concentration-response curves, the largest occurring with the L276A mutant. The impact of these mutations on allosteric modulation by benzodiazepine-site ligands was examined. V279A reduced the potency of both flunitrazepam and Ro15-4513 but, in each case, their efficacy was enhanced. A280S resulted in a decrease in flunitrazepam efficacy without affecting its potency. Additionally, P277A and A280S resulted in Ro15-4513 losing its inverse agonist effect at these receptors. These results suggest that a domain within this small extracellular loop between TMII-TMIII plays a role in determining the sensitivity of GABA(A) receptors to both GABA and benzodiazepine-site ligands.

Allosteric Regulation↗
PubMed2001

The influence of a bupivacaine and fentanyl epidural infusion after epidural fentanyl in patients allowed to ambulate in early labor.

UNLABELLED: Epidural fentanyl after a lidocaine and epinephrine test dose provides adequate analgesia and allows for ambulation during early labor. This study was designed to determine the influence of an epidural infusion of bupivacaine plus fentanyl administered after initiation of epidural labor analgesia with fentanyl. Specifically, we evaluated whether there is an increase in motor block or an increased time to request for further analgesic medication. Fifty-one laboring primigravid women at <5 cm cervical dilation who requested epidural analgesia were enrolled. After a 3-mL epidural test dose of 1.5% lidocaine with epinephrine (5 microg/mL), patients received fentanyl 100 microg via the epidural catheter. They then randomly received either an infusion (10 mL/h) of 0.0625% bupivacaine with fentanyl (3 microg/mL) or an infusion of preservative-free saline. After the administration of the initial analgesic, pain scores and side effects were recorded for each patient at 10, 20, and 30 min, every 30 min thereafter, and at the time of request for additional analgesic medication, by an observer blinded to the technique used. There were no demographic differences between the two groups. The mean duration of analgesia (time from initial dose to request for additional analgesia) was increased in the group that received a continuous infusion of bupivacaine and fentanyl compared with the Saline group (198 +/- 86 vs 145 +/- 50 min; P < 0.009). Side effects were similar between the two groups. No patient in either group experienced any detectable motor block. Fourteen patients chose to ambulate in the Saline group, and 12 patients chose to ambulate in the Infusion group. In early laboring patients, a continuous infusion of 0.0625% bupivacaine infusion with fentanyl (3 microg/mL) prolonged the duration until top-up was required, after epidural fentanyl 100 microg after a lidocaine and epinephrine test dose, and did not cause any clinically detectable motor block. IMPLICATIONS: A 0.0625% bupivacaine and fentanyl (3 microg/mL) infusion, when added to epidural fentanyl (100 microg), prolongs the analgesic duration without increasing motor block in women in early labor.

Adjuvants, Anesthesia↗
PubMed2001

Biomedical image skeletonization: a novel method applied to fibrin network structures.

To understand the rheological behavior of fibrin clots, we must obtain quantitative measurements of morphometric parameters of the networks formed under various conditions. The networks are so complex that researchers must currently manually segment the images of network samples and estimate the parameters from them. Skeletonization is a promising tool for automating this task. We here propose a method that rapidly constructs a coarse representation of a skeleton graph and, using the snake model, deforms the graph to obtain smooth skeletons. Unlike many existing approaches, our method does not involve explicit object boundary information or high order derivatives. Since our method processes a given image as a whole, the presence of multiple objects in an image is automatically detected and the skeletons of these objects are computed simultaneously.

Algorithms↗
PubMed2000

Roles of agonist-binding sites in nicotinic acetylcholine receptor function.

Under equilibrium conditions, the nicotinic acetylcholine receptor from Torpedo electroplax carries two high affinity-binding sites for agonists. It is generally assumed that these are the only agonist sites on the receptor and that their occupancy results in rapid channel activation followed by slower conformational transitions that lead to the high affinity equilibrium state. These slow transitions are thought to reflect the physiological process of desensitization. Here we show that preequilibration of the high affinity sites with saturating concentrations of carbamylcholine does not diminish the ion flux response to subsequent exposure to higher (activating) concentrations of this agonist. This finding has profound implications with respect to receptor function: (1) occupancy of the high affinity sites per se does not desensitize the receptor and (2) these sites cannot be directly involved in receptor activation. It is thus necessary to invoke the presence of additional binding sites in channel opening.

Animals↗
PubMed2000

Endogenous cannabinoid anandamide directly inhibits voltage-dependent Ca(2+) fluxes in rabbit T-tubule membranes.

The effect of the endogenous cannabinoid, anandamide on Ca(2+) flux responses mediated by voltage-dependent Ca(2+) channels was studied in transverse tubule membrane vesicles from rabbit skeletal muscle. Vesicles were loaded with 45Ca(2+) and membrane potentials were generated by establishing K(+) gradients across the vesicle using the ionophore, valinomycin. Anandamide, in the range of 1-100 microM, inhibited depolarization-induced efflux responses. Anandamide also functionally modulated the effects of nifedipine (1-10 microM) and Bay K 8644 (1 microM) on Ca(2+) flux responses. Pretreatment with the specific cannabinoid receptor antagonist, SR141716A (1 microM), pertussis toxin (5 microg/ml), the amidohydrolase inhibitor, phenylmethylsulfonyl fluoride (0.2 mM) or the cyclooxygenase inhibitor, indomethacin (5 microM) did not alter the inhibition of efflux responses by anandamide. Arachidonic acid (10-100 microM) also effectively inhibited 45Ca(2+) efflux from membrane vesicles. In radioligand binding studies, it was found that both anandamide and arachidonic acid inhibited the specific binding of [3H]PN 200-110 to transverse tubule membranes with IC(50) values of 4.4+/-0. 7 and 13.4+/-3.5 microM, respectively. These results indicate that anandamide, independent of cannabinoid receptor activation, directly inhibits the function of voltage-dependent calcium channels and modulates the specific binding of calcium channel ligands of the dihydropyridine class.

Analysis of Variance↗
PubMed2000

Tyrosine 62 of the gamma-aminobutyric acid type A receptor beta 2 subunit is an important determinant of high affinity agonist binding.

The gamma-aminobutyric acid type A receptor (GABA(A)R) carries both high (K(D) = 10-30 nm) and low (K(D) = 0.1-1.0 microm) affinity binding sites for agonists. We have used site-directed mutagenesis to identify a specific residue in the rat beta2 subunit that is involved in high affinity agonist binding. Tyrosine residues at positions 62 and 74 were mutated to either phenylalanine or serine and the effects on ligand binding and ion channel activation were investigated after the expression of mutant subunits with wild-type alpha1 and gamma2 subunits in tsA201 cells or in Xenopus oocytes. None of the mutations affected [(3)H]Ro15-4513 binding or impaired allosteric interactions between the low affinity GABA and benzodiazepine sites. Although mutations at position 74 had little effect on [(3)H]muscimol binding, the Y62F mutation decreased the affinity of the high affinity [(3)H]muscimol binding sites by approximately 6-fold, and the Y62S mutation led to a loss of detectable high affinity binding sites. After expression in oocytes, the EC(50) values for both muscimol and GABA-induced activation of Y62F and Y62S receptors were increased by 2- and 6-fold compared with the wild-type. We conclude that Tyr-62 of the beta subunit is an important determinant for high affinity agonist binding to the GABA(A) receptor.

Amino Acid Sequence↗
PubMed2000

Interaction of a semirigid agonist with Torpedo acetylcholine receptor.

The binding of the semirigid agonist [(3)H]arecolone methiodide to the Torpedo nicotinic acetylcholine receptor has been correlated with its functional properties measured both in flux studies with Torpedo membrane vesicles and by single-channel analysis after reconstitution in giant liposomes. Under both equilibrium and preequilibrium conditions, the binding of arecolone methiodide is similar to that of other agonists such as acetylcholine. At equilibrium, it binds to two sites per receptor with high affinity (K(d) = 99 +/- 12 nM), and studies of its dissociation kinetics suggest that each of these sites is made up of two subsites that are mutually exclusive at equilibrium. The kinetics of arecolone methiodide binding were monitored by the changes in the receptor intrinsic fluorescence, and the data are consistent with a model in which the initial binding event is followed by sequential conformational transitions of the receptor-ligand complex. In flux studies, arecolone methiodide was approximately 3-fold more potent (EC(50) = 31 +/- 5 microM) than acetylcholine but its maximum flux rate was 4-10-fold lower. This phenomenon has been studied further by single-channel analysis of Torpedo receptors reconstituted in giant liposomes. Whereas the flexible agonist carbamylcholine (5 microM) was shown to induce channels with conductances of 56 and 34 pS with approximately equal frequency, arecolone methiodide (2 microM) preferentially induced the channel of lower conductance. These results are interpreted in terms of a simple model in which the rigidity of arecolone methiodide restrains the conformation that the receptor-ligand complex can adopt, thus favoring the lower conductance state.

Animals↗
PubMed2000

Psychosocial predictors of survival: metastatic breast cancer.

BACKGROUND: Research interest in psychosocial predictors of the onset and course of cancer has been active since the 1950s. Recently we reported associations between psychological factors and survival in patients with metastatic melanoma. We now report a replication of this study in a sample of women with metastatic breast cancer. PATIENTS AND METHODS: Ninety-nine patients with metastatic breast cancer completed questionnaires measuring cognitive appraisal of threat, coping, psychological adjustment, perceived aim of treatment, social support and quality of life, approximately four months after diagnosis. Survival was measured from date of study entry to date of death or censored at the date of last follow-up for surviving patients. RESULTS: In a multivariate analysis, four factors independently predicted outcome. Patients with metastases in the liver, lung or pleura survived for a shorter duration (P < 0.001); older patients (P < 0.001) and those with a better appetite (P < 0.05) also lived for a shorter time. Patients who minimised the impact of cancer survived longer (a median of 29.1 vs. 23.9 months after study entry, P < 0.01). CONCLUSIONS: Minimisation was also significantly associated with outcome in patients with metastatic melanoma who participated in an identically designed study, reported elsewhere. This suggests that minimisation may have a general impact on cancer progression and deserves closer scrutiny in other cancers.

Adaptation, Psychological↗
PubMed2000

Patterns over time in quality of life, coping and psychological adjustment in late stage melanoma patients: an application of multilevel models.

BACKGROUND: Quality of life (QOL) assessment is an important component within cancer research. There is often variability in QOL scores both between patients and across time. Understanding this variability in terms of personal characteristics and psychosocial factors would be useful but is often obstructed by the types of analyses that are applied to longitudinal data sets. Improved understanding can be gained with the application of multi-level or hierarchical models that allow for greater flexibility for modelling individual patterns of change over time. METHODS AND PATIENTS: Questionnaires were sent to a cohort of stage IV melanoma patients seen at the Sydney Melanoma Unit between 1991 and 1996, approximately every 3 months for up to 2 years. The data reported here are from a sub-sample of 44 patients who each completed between 3 and 8 questionnaires. Three aspects of QOL were measured (effort to cope, mood and physical well-being), each with a single LASA line. Multilevel techniques were used to model the patterns of QOL over time. Covariates were added to explain variation between patients in their average QOL and change in QOL over time. RESULTS: The scores of each of the three QOL measures showed marked fluctuations over time. However, there was little systematic change during the study in either effort to cope (p = 0.32) or mood (p = 0.06). In contrast, the physical well-being scores of some patients improved while others deteriorated (p < 0.001). On average, physical well-being deteriorated (p < 0.001). Variability between patients accounted for 60% (effort to cope), 45% (mood) and 44% (physical well-being) of the total variance of each scale. A range of psycho-social factors including active and avoidant coping styles and psychological adjustment accounted for significant amounts of the variability between patients in each QOL measure. CONCLUSION: Individual coping and psychological adjustment are related to individual changes in QOL and to differences among patients' QOL. The study illustrates the use of multi-level techniques to further our understanding of differences between patients in their QOL and how it changes over time.

Adaptation, Psychological↗
PubMed2000

Psychosocial predictors of outcome: time to relapse and survival in patients with early stage melanoma.

This study explored psychosocial predictors of relapse and survival in early stage melanoma patients. Patients with locoregional melanoma whose tumour thickness exceeded 0.69 mm, seen at the Sydney Melanoma Unit between 1991 and 1996 participated in the study. Questionnaires were sent to participating patients every 3 months for 2 years. Domains measured included cognitive appraisal of threat, coping, psychological adjustment, quality of life and perceived aim of treatment. Disease and demographic data were obtained from medical records. Multivariate analyses from baseline data used the Cox proportional hazards model. Of the 682 patients invited to participate 426 (62%) agreed. 91 (21%) relapsed and 60 (14%) died within the follow-up period, that ended in October 1997. After controlling for known prognostic indicators, several psychosocial variables predicted time to relapse and/or survival duration. Patients who perceived their aim of treatment to be cured, who did not use avoidance as a coping strategy or who were concerned about their disease experienced longer periods without relapse. Shorter survival duration was associated with a positive mood, the use of avoidance as a coping strategy, not being concerned with their disease and concern about the impact of the disease on family. There is still much to learn about the potential relationships between psychological well being, human behaviours and cancer outcome. Research in this area needs to clarify the psychological processes, as well as understand the biological and/or behavioural mechanisms that may link them to outcome.

Adaptation, Psychological↗
PubMed2000

Characterization of the interaction of zopiclone with gamma-aminobutyric acid type A receptors.

Zopiclone is a cyclopyrrolone that is used clinically as a hypnotic. Although this drug is known to interact with neuronal gamma-aminobutyric acid type A receptors, its binding site(s) within the receptor oligomer has been reported to be distinct from that of the classical benzodiazepines. After photoaffinity labeling with flunitrazepam, receptors in rat cerebellar membranes showed differentially reduced affinity for flunitrazepam and zopiclone by 50- and 3-fold, respectively. Because histidine 101 of the alpha-subunit is a major site of photolabeling, we have made specific substitutions of this residue and studied the consequences on the binding properties of zopiclone and diazepam using recombinant alpha1beta2gamma2-receptors transiently expressed in tsA201 cells. Both compounds showed similar binding profiles with receptors containing mutated alpha-subunits, suggesting a similar interaction with the residue at position 101. At alpha1beta2gamma3-receptors, flunitrazepam affinity was dramatically decreased by approximately 36-fold, whereas the affinity for zopiclone was decreased only 3-fold, suggesting a differential contribution of the gamma-subunit to the binding pocket. Additionally, we used electrophysiological techniques to examine the contribution of the gamma-subunit isoform in the receptor oligomer to ligand recognition using recombinant receptors expressed in Xenopus oocytes. Both compounds are agonists at alpha1beta2gamma2- and alpha1beta2gamma3-receptors, with flunitrazepam being more potent but less efficacious. In summary, these data suggest that histidine 101 of the alpha1-subunit plays a similar role in ligand recognition for zopiclone, diazepam, and flunitrazepam.

Amino Acid Substitution↗
PubMed1999

Evaluation of robot-based registration for subtraction radiography.

Digital subtraction of (plane film) radiographs of an area of interest taken over time is a powerful diagnostic tool. In dentistry for example, this is used to detect and treat periodontal disease (i.e. the sequence of diseases that leads to the loss of bone supporting the teeth). A precondition of subtraction radiography is correct three-dimensional registration of the film and X-ray source, without which the subtraction images are meaningless. A small misalignment can be compensated for by post-processing of the digitized films (by correspondence and rectification) to remove artifacts due to positioning errors. This paper presents a novel approach to subtraction radiography which replaces customary mechanical alignment methods (such as a stent or cephalostat) with a robot. A mechanical stent is a short rod attached at one end to the X-ray source and at the other to a mechanical appliance protruding from the patient's mouth. An experimental system was constructed which creates a 'sensorized stent' by integrating a plastic mouth appliance (with the impression of the patient's teeth), a robot carrying an X-ray source and a host computer. Results showed that the robotic system was superior to the mechanical alignment approach, due to its excellent accuracy and repeatability. This resulted in much less variation in the non-registered X-ray images, and in a smaller standard deviation in the intensities of subtracted images overall. The results suggest that in the future, diagnostic studies including subtraction radiography will not need either mechanical alignment (which is imprecise) or post-processing registration (which is time consuming).

Cadaver↗
PubMed1999

Misunderstanding in cancer patients: why shoot the messenger?

AIM: We aimed to document the prevalence of misunderstanding in cancer patients and investigate whether patient denial is related to misunderstanding. PATIENTS AND METHODS: Two hundred forty-four adult cancer outpatients receiving treatment completed a survey assessing levels of understanding and denial. Doctors provided the facts against which patient responses were compared. Multiple logistic regression analyses determined the predictors of misunderstanding. RESULTS: Most patients understood the extent of their disease (71%, 95% CI: 65%-77%) and goal of treatment (60%, 95% CI: 54%-67%). Few correctly estimated the likelihood of treatment achieving cure (18%, 95% CI: 13%-23%), prolongation of life (13%, 95% CI: 8%-17%) and palliation (18%, 95% CI: 10%-27%). Patient denial predicted misunderstanding of the probability that treatment would cure disease when controlling for other patient and disease variables (OR = 2.20, 95% CI: 0.99-4.88, P = 0.05). Patient ratings of the clarity of information received were also predictive of patient understanding. CONCLUSIONS: Patient denial appears to produce misunderstanding, however, doctors' ability to communicate effectively is also implicated. The challenge that oncologists face is how to communicate information in a manner which is both responsive to patients' emotional status and sufficiently informative to allow informed decision-making to take place.

Adaptation, Psychological↗
PubMed1999

Barriers to participation in randomized clinical trials for early breast cancer among Australian cancer specialists.

BACKGROUND: Doctors' discomfort with the randomized trial process may significantly impact on accrual rates to clinical trials. However, there is little information regarding factors that influence accrual to clinical trials in Australia. The present study examines Australian cancer specialists' attitudes towards and participation in current breast cancer clinical trials. METHODS: All medical and radiation oncologists across Australia and surgeons listed as participants in the Australian and New Zealand Breast Cancer Trials Group were sent questionnaires assessing attitudes towards and participation in current clinical trials for early stage breast cancer. RESULTS: The response rate was 71% (269/381). The mean age of respondents was 45 years and 85% were male. Respondents estimated that a mean of 5.2 (SD = 8.2) of their patients had been enrolled in a breast cancer clinical trial in the previous 12 months. Participation (in any trial) by medical oncologists (60.6%, 95% CI 54.5-66.7%) and surgeons (63.1%, 95% CI 57.1-69.1%) was significantly higher than for radiation oncologists (43.2%, 95% CI 37-49.4%, P = 0.03). The major barriers to participation in current breast cancer trials were lack of resources (44%) or issues related to specific trials (44%; e.g. relevance of the research questions or choice of standard therapies). CONCLUSIONS: The results of this study suggest that efforts to improve doctors' participation in clinical trials need to address a number of issues. More empirical research is needed to evaluate new strategies to raise participation in clinical trials.

Adult↗