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Biomedical subjects

S Dunn

Publications and source records attributed to S Dunn.

At least 19 recordsLinked to original sources
PubMed2006

Initial results of screening of nondiabetic organ donors for expression of islet autoantibodies.

CONTEXT: Type 1A diabetes is characterized by a long prodromal phase during which autoantibodies to islet antigens are present. Nevertheless, we lack data on the pancreatic pathology of subjects who are positive for islet autoantibodies (to islet autoantigens GAD65, insulin, and ICA512). OBJECTIVE: In this manuscript, we describe a novel strategy in obtaining pancreata and pancreatic lymph nodes from islet autoantibody-positive organ donors that involves careful coordination among the laboratory and the organ donor provider organization. DESIGN: We developed a rapid screening protocol for islet autoantibodies measurement of organ donors to allow identification of positive subjects before organ harvesting. In this way we were able to obtain pancreata and pancreatic lymph nodes from subjects with and without islet autoimmunity. SETTING: The organ donors used in this study were obtained from the general community. SUBJECTS: The population studied consisted of 112 organ donors (age range 1 month to 86 yr, mean age 39 yr). MAIN OUTCOME MEASURE: The main outcome measure of this study consisted of evaluating the pancreatic histology and identify T cells autoreactive for islet antigens in the pancreatic lymph nodes. RESULTS: To date we have identified three positive subjects and obtained the pancreas for histological evaluation from one of the autoantibody-positive donors who expressed ICA512 autoantibodies. Although this subject did not exhibit insulitis, lymphocytes derived from pancreatic lymph nodes reacted to the islet antigen phogrin. CONCLUSION: In summary, these results indicate that it is possible to screen organ donors in real time for antiislet antibodies, characterize pancreatic histology, and obtain viable T cells for immunological studies.

Adolescent↗
PubMed2006

Regimens of misoprostol with mifepristone for early medical abortion: a randomised trial.

OBJECTIVE: To compare the efficacy, adverse effects and acceptability of the three most common misoprostol regimens used with mifepristone for medical abortion. DESIGN: Randomised nonblinded trial. SETTING: Three clinics associated with major research universities in Canada; two in major urban areas and one in a periurban area. POPULATION: Women of reproductive age. METHODS: Consenting women presenting for abortion services with gestations less than 56 days and who met inclusion criteria were given 200 mg mifepristone orally and then randomised into three misoprostol study groups: (group I) 400 micrograms of oral misoprostol, (group II) 600 micrograms of oral misoprostol, and (group III) 800 micrograms of vaginal misoprostol. Misoprostol was self-administered at home 24-48 hours following mifepristone, and participants were instructed to take a second similar misoprostol dose at 24 hours after the initial dose if bleeding was less than a normal menstrual period. MAIN OUTCOME MEASURES: Successful abortion without surgery was 94.1%, with no significant differences across the three study groups (94.7% in group I, 93.4% in group II, and 94.3% in group III; P= 0.975). RESULTS: Efficacy and adverse effects did not differ significantly across the three study groups. Pain increased significantly across the study and the gestational age groups and was associated with lower acceptability. CONCLUSIONS: There appears to be a range of safe and effective options for early medical abortion with mifepristone including a choice between oral and vaginal administration of misoprostol.

Abortifacient Agents, Nonsteroidal↗
PubMed2006

Development and assessment of conventional and targeted drug combinations for use in the treatment of aggressive breast cancers.

Combination chemotherapy has been at the forefront of cancer treatment for over 40 years. However, the rationale for selecting drug combinations and the process used to demonstrate clinical effectiveness has primarily followed trial and error methodology. Typically, the selection and assessment of combined drug therapies has been based on the effectiveness of each agent as monotherapy in treating the neoplasm and avoiding overlapping toxicities, followed by clinical trials to establish dose scheduling, toxicity, and efficacy. Unfortunately, this scheme is inefficient in terms of the time required to complete and revise these clinical trials based on the outcome to optimize the drug combination. A more rational approach for the development of combination oncology products should consider (i) in vitro assays for assessing therapeutic effects of drug combinations (antagonistic, additive or synergistic interactions) when added simultaneously; (ii) methods for measuring these interactions in vivo; (iii) the importance of understanding pharmacokinetic and biodistribution parameters when using drug combinations; (iv) the need to assess pathways known to contribute to cancer cell survival as well as metastasis; and (iv) the need to assess the fate of different cell populations (cancer and stroma) contributing to the development of cancer. Therefore, the goal of this article is to provide a road map for the preclinical development of drug combination products that will have improved therapeutic activity and a high likelihood of providing beneficial therapeutic outcomes in patients with aggressive cancers with a specific focus on patients with breast cancer.

Animals↗
PubMed2004

Surface diagnostics for scale analysis.

Stainless steel, polymethylmethacrylate and polytetrafluoroethylene coupons were analysed for surface topographical and adhesion force characteristics using tapping mode atomic force microscopy and force-distance microscopy techniques. The two polymer materials were surface modified by polishing with silicon carbide papers of known grade. The struvite scaling rate was determined for each coupon and related to the data gained from the surface analysis. The scaling rate correlated well with adhesion force measurements indicating that lower energy materials scale at a lower rate. The techniques outlined in the paper provide a method for the rapid screening of materials in potential scaling applications.

Chemical Precipitation↗
PubMed2003

Selection of continence products: perspectives of people who have incontinence and their carers.

PURPOSE: The needs, issues and concerns of people with incontinence and their carers were explored in order to inform the development of a comprehensive Australian consumer guide to continence products. PARTICIPANTS AND METHODS: Semi-structured interviews and focus groups were conducted with a wide range of people with incontinence and carers. Questions centred around issues and concerns regarding continence product selection, what information people need to make informed choices, and how the information should be presented. Qualitative analysis highlighted common themes and specific issues. RESULTS: Issues raised by consumers included the paucity of written information currently available, ignorance among health professionals concerning continence products and the lack of information about sources of help. Most consumers selected products by trial and error and were unaware of the range of products and services available. They wanted a consumer guide to continence products to be user-friendly and easily accessible, with information on product availability, cost, quality, comfort and design. They also wanted more general information on incontinence, sources of help, and how to select, care for and dispose of products. Participants wanted the guide to be made available in different languages, in large print and simple language. CONCLUSIONS: The findings highlight the need and provide a framework for a consumer guide and information on continence products.

Australia↗
PubMed2003

The potential therapeutic role of statins in central nervous system autoimmune disorders.

3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, 'statins' are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of mevalonate are also involved in posttranslational modification of specific proteins involved in cell proliferation and differentiation. Thus, statins have important biologic effects that may be independent of their cholesterol-reducing properties. Recent studies indicate that statins have antiinflammatory and neuroprotective properties which may be beneficial in the treatment of multiple sclerosis as well as other central nervous system (CNS) neurodegenerative diseases. This article will outline current experimental evidence that may suggest potential clinical benefits for patients with CNS autoimmune disorders. Ultimately, clinical trials will have to determine the safety and efficacy of statins in this patient population.

Animals↗
PubMed2002

Growing pains.

Explore the source record for details and available documents.

Abdominal Pain↗
PubMed2001

Three-dimensional MR microscopy of a transgenic mouse model of dilated cardiomyopathy.

BACKGROUND: Scientists are now able to alter the genetics of vertebrate embryos routinely to produce animal models of human developmental diseases. However, our understanding of structural changes in these animal models is limited by current methodologies. Histological techniques, although providing great anatomic detail, display only "static" data (one time point only) in two dimensions. Ultrasound may be used to generate continuous time course data, but is limited by interobserver variation, limited acoustic windows, and relatively low resolution. OBJECTIVE: To apply the high resolution, non-destructive, and three-dimensional acquisition capabilities of magnetic resonance (MR) microscopy to compare the hearts of normal mice versus an established transgenic mouse model of dilated cardiomyopathy. MATERIALS AND METHODS: Transgenic mice exhibiting dilated cardiomyopathy were developed via the introduction of a mutated, heart-specific gene (myosin light chain). Postmortem cardiac imaging was performed on the transgenic mice and normal controls. MR imaging was performed on a Bruker 3T imaging magnet using a custom radiofrequency coil following contrast perfusion of the atrial and ventricular chambers. Image resolution was 156 microm isotropic voxels. MR images were compared to gross pathologic specimens. Imaging data were post-processed using custom software to calculate the volumes of the atria and ventricles and to display the three-dimensional morphology of the chambers and myocardium. RESULTS: Of the seven mice scanned, four exhibited normal right atrial (average = 14.8 microl +/- 1.4), left atrial (average = 8.5 microl +/-0.3), right ventricular (average = 12.9 microl +/-2.7), and left ventricular (average 3.3 microl +/-0.5) volumes. Three mice exhibited dilatation of the right and left cardiac chambers (RA average = 23.9 microl +/-5.6; LA average = 15.9 microl +/-4.8; RV average = 32.5 microl +/- 6.8; LV average 24.0 microl +/-1.4). The gross morphology was verified upon autopsy of the animals and correlated with the animal's genotype. The differences in volumes between the normal and dilated cardiomyopathy mice were statistically significant (P values ranged from 0.001 to 0.024 for the different chambers). CONCLUSION: MR microscopy is a potentially useful tool for developmental biology research. The imaging of mouse hearts is feasible, and these methods provide quantitative and qualitative morphologic data of a mouse model of dilated cardiomyopathy not available using traditional methods.

Animals↗
PubMed2001

Factors influencing job valuation: a comparative study of critical care and non-critical care nurses.

This study sought to identify the relationship between three predictor variables, perceived collaboration with medical staff, autonomy and independent actions and an outcome, the value hospital nurses placed on their work. In total 189 critical care and 366 non-critical care nurses completed a mailed survey. Critical care nurses perceived themselves to have a more collaborative relationship with the medical staff, described performing actions independent of medical orders more frequently and perceived their jobs to have more value than non-critical care nurses. However the latter group perceived themselves to have more autonomy in their work. Within both groups collaboration and autonomy were significantly, but weak to moderately correlated with job valuation. Simply expanding the work hospital nurses do is unlikely to result in nurses valuing their jobs more, however promoting an environment of respect and sharing between the medical and nursing staff and supporting nurses when they act in an autonomous fashion may positively influence nurses' perceptions of their work.

Adult↗
PubMed2001

Cohesion among nurses: a comparison of bedside vs. charge nurses' perceptions in Australian hospitals.

AIM: This study examines the extent to which hospital nurses view their working environment in a positive sense, working as a cohesive group. BACKGROUND: Despite the fact that nursing in Australia is now considered a profession, it has been claimed that nurses are an oppressed group who use horizontal violence, bullying and aggression in their interactions with one and other. METHODS: After ethical approval, a random sample of 666 nurses working directly with patients and all 333 critical care nurses employed in three large tertiary Australian hospitals were invited to participate in the study in the late 1990s. A mailed survey examined the perceptions of interaction nurses had with each other. The hypothesis, that level of employment (either Level I bedside nurses or Level II/III clinical leaders) and area of work (either critical care or noncritical care) would influence perceptions of cohesion, as measured by the cohesion amongst nurses scale (CANS) was tested. RESULTS: In total 555 (56%) surveys were returned. Of these, 413 were returned by Level I and 142 by Level II/III nurses. Of this sample, 189 were critical care and 355 noncritical care nurses. There was no difference between Level I and II/III nurses in mean CANS scores. It is interesting to note that the item rated most positively was "nurses on the units worked well together", however, the item rated least positive was "staff can be really bitchy towards each other" for both Level I and II/III nurses. There was no difference in CANS scores between critical care and noncritical care nurses. CONCLUSIONS: Nurses working in Australian hospitals perceived themselves to be moderately cohesive but, as would be expected in other work settings, some negative perceptions existed.

Adult↗
PubMed2001

Lineage specific differentiation of pluripotent cells in vitro: a role for extraembryonic cell types.

The controlled differentiation of pluripotent cells will be a prerequisite for many cell therapies. We have previously reported homogeneous conversion of embryonic stem (ES) cells in vitro to early primitive ectoderm-like (EPL) cells, equivalent to early primitive ectoderm, an obligatory differentiation intermediate between ES cells and somatic cell populations. Early primitive ectoderm-like cells differentiated within aggregates form mesodermal lineages at the expense of ectoderm. In this work we demonstrate that the failure of EPL cells to form ectodermal cell types does not reflect an inherent restriction in developmental potential. Early primitive ectoderm-like cells form ectodermal derivatives such as neurons in response to neural inducers such as retinoic acid, or when differentiated in the environment provided by ES cell embryoid bodies. This could be explained by signals from the extraembryonic cell type visceral endoderm which forms in differentiating ES cell but not EPL cell aggregates. Consistent with this possibility, culture of EPL cell aggregates in the presence of visceral endoderm-like signals did not prevent differentiation of the pluripotent cells, but resulted in suppression of mesoderm formation. These results suggest a role for visceral endoderm in regulation of germ layer specification from pluripotent cells, and can be integrated into a model for cell differentiation in vitro and in vivo.

Blotting, Northern↗
PubMed2001

Association between ACE gene polymorphism and diabetic nephropathy in South Indian patients.

OBJECTIVE: To study the association of ACE gene polymorphism and diabetic nephropathy in South Indian subjects. SETTING: Outpatient clinic of a specialized hospital. PATIENTS: The study included 109 South Indian type 2 diabetic patients (72 males and 37 females; age 56.7 plus/minus 9.0 years, mean plus/minus SD). The patients were subdivided into two groups: nephropathic (n=86) and normoalbuminuric patients (n=23). INTERVENTIONS: Genomic DNA was isolated from the peripheral blood leukocytes. To determine the ACE genotype, genomic DNA was amplified by PCR initially using a flanking primer pair and, subsequently when necessary, with a primer pair that recognizes the insertion specific sequence for confirmation of the specificity of the amplification reactions. MAIN OUTCOME MEASURES: ACE genotype distribution in the two study groups. RESULTS: In the nephropathic patients, ID and DD genotypes were present in 52.3% and 27.9% of the patients, respectively as compared to 34.8% and 21.7% respectively in those with normoalbuminuria. The D allele was present in 80.2% of the nephropathic patients and 56.5% of the normoalbuminuric patients (chi-squared=4.28, P=0.039; odds ratio 3.12). Therefore, the higher percentage of II genotype in the normoalbuminuric group was 43.5% as compared to the 19.8% in nephropathic patients. CONCLUSIONS: This study showed a positive association between the D allele (ID and DD genotype) of the ACE polymorphism and diabetic proteinuria in South Indian type 2 diabetic patients. Our findings are in keeping with several earlier studies showing a strong association of the D allele of the ACE gene with diabetic nephropathy.

Alleles↗
PubMed2000

Neoral use in the pediatric transplant recipient.

This review and critical analysis of current trends of immunosuppression management in pediatric transplantation provides evidence and support for the continued role of Neoral as an indispensable part of immunosuppressive protocols. CyA formulation influences clinical outcomes such as acute rejection, as confirmed by two studies. The CyA microemulsion formulation provides more reliable and effective absorption. An advanced TDM strategy to determine CyA bioavailability can improve the effectiveness and safety of immunosuppression in de novo liver transplant patients. especially in the younger de novo patient. Neoral is an indispensable part of combination protocols in pediatric transplantation.

Child, Preschool↗
PubMed2000

The patients' perception of recovery after coronary angioplasty.

Coronary angioplasty and stent placement is associated with short hospital stays. Patients are expected to recover at home, alone, following limited care time with nurses. The purpose of the study was to describe participants' perceptions of recovery after angioplasty. Eight men and three women were interviewed 1 month after discharge from hospital. Verbatim transcripts were analysed for major themes using the qualitative techniques of grounded theory. Data analysis revealed three major categories: awareness of the problem, coping response and appraisal of the situation. These were linked via a problem solving process. In step one, the problem was identified. In step two, coping responses were taken to try and solve the problem. In step three, the results of the coping responses were appraised or evaluated. These categories were further defined by four phases identified as: pre-admission, admission, during the angioplasty and recovery. This paper describes the recovery phase. Awareness of the problem in the recovery phase was associated with 'relief from chest pain' for most participants. In contrast, anxiety continued and was associated with 'uncertainty over future health'. Participants described coping responses of "taking control of their life again" by undertaking both physical and psychological strategies. Finally, the situation was appraised to be either a 'good' or a 'bad' recovery. This appraisal was based on such considerations as the absence of chest pain, improvement in well-being and energy levels. The results of this study highlight patients' concerns and support the need for greater emphasis on their psychosocial needs. This care must be provided within the time constraints of short hospital stays. Nurses must also consider providing support to patients in the pre-admission and recovery phases.

Adaptation, Psychological↗