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Biomedical subjects

M Boyle

Publications and source records attributed to M Boyle.

At least 19 recordsLinked to original sources
PubMed1997

Intramarrow cytokine gene transfer by adenoviral vectors in dogs.

Daily systemic administration of hematopoietic growth factors can be associated with dose-limiting systemic side effects. To overcome this, we have investigated hematopoietic cytokine gene transfer to the marrow cavity of dogs by direct intramarrow injection of adenoviral vectors. In marrow culture, replication-deficient (E1-deleted) adenoviral vectors were able to transduce marrow stromal cells, demonstrating 30-fold greater expression than from other marrow cell types. High-level (ng/ml) cytokine production from transduced stromal cells persisted for 14 days in culture. Because adenovectors could efficiently transduce marrow stromal cells in culture, we investigated if stromal cells could also be transduced in vivo following direct intramarrow vector injection. Adenovectors with genes for interleukin 6 (IL-6) and Lac Z (beta-galactosidase) were injected directly into the marrow cavity of dogs resulting in protein expression localized to within the treated marrow. To evaluate this approach further in dogs, we constructed a vector expressing biologically active canine granulocyte-macrophage colony stimulating factor (GM-CSF). 293 cells infected with ADGM-CSF demonstrated prevalent GM-CSF mRNA by Northern blot and 135 +/- 30 ng/ml of protein as measured by enzyme-linked immunosorbent assay (ELISA). In vitro bioactivity of protein expressed was confirmed by canine GM colony-forming assay (CFU-GM). In vivo high-level protein production was noted in supernatants of marrow aspirates 72 hr following direct intramarrow administration of ADGM-CSF (baseline mean +/- SEM, 27 +/- 22 ng/ml, 72-hr sample 921 +/- 461 ng/ml). A localized myeloid expansion of marrow and significant peripheral leukocytosis (neutrophilia) were noted in all ADGM-CSF-treated dogs. Peripheral blood changes lasted for up to 3 weeks in dogs following single intramarrow injection. Thus, adenoviral cytokine expression from the marrow of a single large bone (ilium) led to compartmentalized expression of growth factor and an increase of hematopoiesis sufficient to cause peripheral blood changes in a large animal model.

Adenoviridae↗
PubMed1997

Homodimerization of erythropoietin receptor by a bivalent monoclonal antibody triggers cell proliferation and differentiation of erythroid precursors.

Erythropoietin (EPO) stimulates proliferation and differentiation of erythroid progenitor cells. Several lines of evidence indicate that the most likely mechanism of EPO receptor (EPO-R) activation by EPO is homodimerization of the receptor on the surface of erythrocyte precursors. Therefore, we argued that it should be possible to raise EPO-R monoclonal antibodies (MoAbs) that would activate the receptor by dimerization and thus mimic EPO action. We have identified such an agonist MoAb (MoAb34) directed against the extracellular EPO binding domain of the EPO-R. This bivalent IgG antibody triggers the proliferation of EPO-dependent cell lines and induces differentiation of erythroid precursors in vitro. In contrast, the monovalent Fab fragment, which cannot dimerize the receptor, is completely inactive. The mechanism of receptor activation by homodimerization implies that at high ligand concentrations the formation of 1:1 receptor/ligand complexes is favored over 2:1 complexes, thereby turning the ligand agonist into an antagonist. Thus, EPO and MoAb34 should self-antagonize at high concentrations in both cell proliferation and differentiation assays. Our data indeed demonstrate that EPO and MoAb34 antagonize ligand-dependent cell proliferation with IC50 values of approximately 20 and 2 mumol/L, respectively. Erythroid colony formation (BFUe) is inhibited at MoAb34 concentrations above 1 mumol/L. Furthermore, we analyzed the MoAb34:EPO-R interaction using a mathematic model describing antibody-mediated receptor dimerization. The data for proliferation and differentiation activity were consistent with the receptor dimer formation on the cell surface predicted by the model.

Animals↗
PubMed1997

Assessment of the agreement between cardiac output measured by bolus thermodilution and continuous methods, with particular reference to the effect of heart rhythm.

Cardiac output (CO) is a fundamentally important haemodynamic parameter and its continuous measurement has the potential to enable early recognition of haemodynamic trends and earlier therapeutic response. A method of continuous cardiac output (CCO) monitoring is now available for clinical use. The accuracy and reliability of this method has been confirmed in clinical trials but not, to our knowledge, in the presence of abnormal heart rhythms. A comparison was made between CCO and bolus thermodilution methods, to determine if there is a greater difference between their respective determinations of CO when heart rhythm is abnormal. A convenience sample of 38 intensive care patients was used to obtain 410 comparisons of CCO and bolus CO determinations. Heart rhythm associated with each comparison was determined. The comparison produced a measurement bias of -0.07 l/min and limits of agreement of -1.77 to 1.63 l/min. The bias of the two measurements was -0.35 l/min for sinus rhythm, -0.19 l/min for sinus tachycardia and -0.12 l/min for atrial flutter/fibrillation. Increased temperature and heart rate did not affect measurement agreement. In conclusion, the agreement between the bolus and continuous methods is clinically acceptable and is unaffected by the heart rhythms of sinus rhythm, sinus tachycardia and atrial flutter/fibrillation.

Arrhythmias, Cardiac↗
PubMed1997

Expression and function of clift in the development of somatic gonadal precursors within the Drosophila mesoderm.

The gonad forms from cells of two lineages: the germline and soma. The somatic gonadal cells generate the various cell types within the testis or ovary that support gametogenesis. These cells derive from embryonic mesoderm, but how they are specified is unknown. Here, we describe a novel regulator of Drosophila gonadogenesis, clift, mutations in which abolish gonad formation. clift is expressed within somatic gonadal precursors as these cells first form, demonstrating that 9-12 cells are selected as somatic gonadal precursors within each of three posterior parasegments at early stages in gonadogenesis. Despite this early expression, somatic gonadal precursors are specified in the absence of clift function. However, they fail to maintain their fate and, as a consequence, germ cells do not coalesce into a gonad. In addition, using clift as a marker, we show that the anteroposterior and dorsoventral position of the somatic gonadal precursor cells within a parasegment are established by the secreted growth factor Wg, coupled with a gene regulatory hierarchy within the mesoderm. While loss of wg abolishes gonadal precursors, ectopic expression expands the population such that most cells within lateral mesoderm adopt gonadal precursor fates. Initial dorsoventral positioning of somatic gonadal precursors relies on a regulatory cascade that establishes dorsal fates within the mesoderm and is subsequently refined through negative regulation by bagpipe, a gene that specifies nearby visceral mesoderm. Thus, these studies identify essential regulators of gonadal precursor specification and differentiation and reveal novel aspects of the general mechanism whereby distinct fates are allocated within the mesoderm.

Alleles↗
PubMed1997

Childhood sexual and physical abuse. Incidence in patients with vulvodynia.

OBJECTIVE: To compare the incidence of sexual and/or physical abuse in women with vulvodynia (chronic, burning vulvar pain in the absence of clear medical findings) as compared to women with chronic vulvar symptoms due to specific, objective vulvar disease and with women from a general dermatology practice. STUDY DESIGN: An invitation to participate in this questionnaire study was sent to 300 women over 18 years of age from a vulvo-vaginal clinic and 280 women from a general dermatology practice. These questionnaires asked for basic demographic information as well as information on childhood sexual experiences and physical abuse. RESULTS: Questionnaires from 89 patients with vulvodynia, 65 patients with chronic vulvar symptoms due to specific, objective vulvar disease and 166 patients from a general dermatology practice were examined. There were no differences as to the incidence of childhood sexual or physical abuse between patients with vulvodynia and either those with general dermatology complaints or those with chronic vulvar symptoms due to objective disease. CONCLUSION: There is no evidence from these data that women with vulvodynia experience a higher incidence of sexual or physical abuse during childhood as compared to women in a general dermatology office or women with chronic vulvar symptoms from specific, observable pathology.

Adult↗
PubMed1996

Attitudes of in vitro fertilization and intrauterine insemination couples toward multiple gestation pregnancy and multifetal pregnancy reduction.

OBJECTIVE: To determine attitudes regarding multiple pregnancy and multifetal pregnancy reduction in couples embarking on gonadotropin therapy. DESIGN: Questionnaire given to couples initiating gonadotropin therapy. SETTING: University hospital-based infertility unit. PATIENTS: Twenty-seven couples undergoing IVF and 50 couples undergoing IUI. RESULTS: The groups' responses tended to be quite similar, with all groups reporting declining favorability ratings as the fetal order increased. The IUI group did feel more favorable than the IVF group toward all gestational outcomes and less favorable toward multifetal pregnancy reduction. A history of live births and length of infertility had no significant impact on the results. CONCLUSION: Couples undergoing gonadotropin therapy have an overall favorable attitude toward multiple gestational pregnancies of triplets or twins and an increased willingness to consider multifetal pregnancy reduction for quadruplets and more.

Attitude↗
PubMed1996

Paraganglioma of the prostatic urethra. A report of three cases and a review of the literature.

OBJECTIVE: To determine the incidence and clinical presentation of prostatic urethral paragangliomas and to compare these findings with paragangliomas occurring in the other sites of the lower urinary tract. PATIENTS AND METHODS: The clinical records of three patients with prostatic urethral paragangliomas were reviewed, as was the histology of each specimen. The tumours were stained immunocytochemically with neuron-specific enolase, chromogranin, S100 protein, protein gene product 9.5, prostate-specific acid phosphatase and prostate-specific antigen. RESULTS: The three tumours occurred in elderly men, two of whom presented with haematuria, one of whom also had a vesical transitional cell carcinoma, and the third patient had obstructive symptoms due to co-existent prostatic hyperplasia. The histological appearances and immunocytochemical findings were consistent with paraganglioma. Treatment consisted of local excision and there were no recurrences or metastases at 5 and 6 years in two patients for whom follow-up was available. CONCLUSION: Urethral paragangliomas are rare tumours arising in elderly men and are hormonally inactive. Although haematuria may be the presenting symptom, it is important to exclude additional more common and possibly more sinister lesions such as transitional cell carcinoma. Local excision appears to be curative.

Aged↗
PubMed1996

A high-risk pilot study of the children of adults with social phobia.

OBJECTIVE: Children of patients with social phobia were studied to estimate their rates of psychiatric disorder. METHOD: Twenty-six social-phobic outpatients who had at least one child between the ages of 4 and 18 years participated in the study. Information was collected from parents on all 47 children and from the children between 12 and 18 years of age. Diagnoses in the children were made based on DSM-III-R and were done by a best-estimate method, using parent and child reports from a modified Anxiety Disorders Interview Schedule for Children, the Survey Diagnostic Instrument, the Current Self-Report Childhood Inhibition Scale, and the Alcohol Dependence Survey. RESULTS: Of the 47 children, 49% had at least one lifetime anxiety disorder diagnosis. The most common diagnoses were overanxious disorder (30%), social phobia (23%), and separation anxiety disorder (19%). Sixty-five percent had more than one anxiety disorder diagnosis. Lifetime major depression was found, in 8.5% of the children. Parents whose children met criteria for an anxiety disorder had a greater mean number of comorbid diagnoses than did the parents of unaffected children. CONCLUSION: This pilot study suggests that children of social-phobic parents may have increased rates of psychiatric disorder. Further studies incorporating a control group are needed.

Adolescent↗
PubMed1996

Repeat neurobehavioral study of borderline personality disorder.

Previous research has tentatively identified a large subgroup of patients with borderline personality disorder (BPD) with histories of developmental or acquired brain insults. Similarly, these studies have demonstrated a possible biological correlation between the severity of BPD and the number of previous brain insults. The possibility of frontal system cognitive dysfunction in BPD has been raised. This single-blind, case-control study of BPD showed that 13 of 24 subjects with BPD had suffered a brain insult. Correlations between neurodevelopmental/acquired brain injury score and the diagnostic interview for borderline (DIB) score (r = 0.47), and between frontal system cognitive functioning and DIB score (r = -0.37) were seen. Neurocognitive testing and comparison with a cohort of subjects with traumatic brain injury (TBI) showed a pattern of similar cognitive functioning between the 2 groups, with the only differences on individual tests being in the direction of worse functioning in the group with BPD on 2 tasks. These results support the hypotheses described above. The main limitation reflects the low numbers of subjects.

Adult↗
PubMed1996

The arteriovenous fistula for hemodialysis access: gold standard or archaic relic?

A five year retrospective review was undertaken to evaluate the patency rates of arteriovenous fistulae (AVF) in patients with end stage renal disease. From July 1989 through June 1994, 150 fistulae were created in the wrists of 144 patients. Thirty-four percent of the patients had diabetes mellitus. Patient death or irreparable fistulae were considered end points in the study. Patency rates were calculated by the Kaplan-Meier Actuarial Analysis. An analysis to assess the impact of the demographic characteristics, underlying renal disease, and effect of revisions on patency rates was calculated. The results demonstrate a high initial failure rate (less than 1 month) of 13 per cent in the entire cohort undergoing fistulae replacement. The 1 and 5-year patency rates were 56 per cent and 30 per cent, respectively. Diabetics had a significantly lower patency rate at 1 and 5 years (42% and 18%) respectively. Others, who had poor patency rates, include patients 70 years old or greater (40% patency at one year). The results suggest that the AVF should not be the first choice of access in elderly diabetics and that these patients would be better served with other modes of access, such as synthetic conduits or permanent indwelling venous catheters.

Adult↗
PubMed1996

Reproducibility of Bayesian belief network assessment of breast fine needle aspirates.

OBJECTIVE: To assess the consistency of diagnosis of fine needle aspiration biopsies of breast lesions by three experienced and five less experienced pathologists using conventional means and applying a Bayesian belief network (BBN) to 10 diagnostic features to support diagnostic decision making. STUDY DESIGN: Forty fine needle aspiration biopsies, previously assessed by one of the experienced pathologists both conventionally and using a BBN, were assessed by two further experienced pathologists and five less experienced pathologists. RESULTS: Using the BBN, the experienced pathologists arrived at diagnoses in agreement with an established consensus at a slightly lower rate than by conventional means. The less experienced pathologists arrived at the correct diagnoses no more frequently with the help of the BBN than conventionally. CONCLUSION: As used in this study, the BBN did not help less experienced pathologists to interpret their observations but did not enable less experienced pathologists to identify how their observations differed and affected their diagnoses. The prototype system used in this study has since been upgraded by providing computer graphic displays of the features to be observed so that a more uniform mental image can be held by the participating pathologists. This will be tested with the same study design.

Biopsy, Needle↗
PubMed1995

Nitric oxide: a positive poison.

In 1987 the demonstration that nitric oxide (NO) was formed in vascular endothelial cells opened up a vast area of research. Ten years ago NO was viewed primarily as a toxic gas related to air pollution. Today NO is recognised as a major endogenous mediator of multiple physiological processes. NO's vasodilatory properties and short half life has led to the use of inhaled NO as a selective pulmonary vasodilator. NO was first used in neonates with acute pulmonary hypertension. It is now being used in the treatment of critically ill adults with severe respiratory compromise. It is very likely that intensive care nursing staff will increasingly be asked to contribute to the maintenance and management of NO inhalation therapy.

Aged↗
PubMed1995

Comparative clearance performance of two dialyser units used in the CVVHD mode.

Continuous renal replacement therapies are now commonly used modes of support in acute renal failure (ARF). This study compared the clearance performance and it's degradation over time of two dialysers, one of flat plate configuration, and one of hollow fibre configuration (Asahi PAN 06 hollow fibre dialyser, Domedica, Sydney, and Hospal AN69HF flat plate dialyser, Gambro, Sydney) used in the CVVHD mode. Data were obtained from seven patients. Urea clearance was determined at commencement of dialysis and then at 12 hour intervals up to 48 hours post commencement. At each study time, urea clearance was determined at dialysis fluid (DF) flows of 500, 1000, 1500 and 2000 ml/hr. The procedure was repeated for each patient using the alternate dialyser. Comparisons of the two dialyser's urea clearance did not demonstrate any significant difference at any of the time periods studied. Overall, clearance was dependent upon (DF) flow with the diffusive clearance initially equal to DF flow but falling to 0.7 and 0.85 times increase in DF flow at 48 hours.

Acute Kidney Injury↗
PubMed1995

The development of the Australian Basic Intensive Care Knowledge Test.

The Basic knowledge Assessment Tool (BKAT), a test developed in the United States, has been presented as a valid and reliable test of basic knowledge for critical care nursing. However, it was necessary to determine the BKAT's validity and reliability in the Australian intensive care (IC) context. The Delphi technique, utilising a panel of eleven experts, was used to determine the content validity of the BKAT. The Delphi process resulted in the development of a test with 105 questions. These questions consist of 49 original BKAT questions, 25 original BKAT questions slightly modified, 3 original BKAT questions with major modifications and 28 new questions. A criterion group design was used to establish the modified test's reliability and decision validity. Item analysis was undertaken using item difficulty and item discrimination indexes. The modified test was completed by 14 registered nurses with no IC experience, 18 registered nurses with intermediate IC experience and 25 registered nurses qualified as intensive care specialists. The mean score (and standard deviation) for the test for each of the respective groups was 41(9), 69(9) and 86(7). These results were significantly different (p < 0001). The reliability was established with a Cronbach Alpha coefficient of .96. The modified test is a reliable and valid measure of IC basic knowledge and can be used as a valuable adjunct in the assessment of IC orientation programs.

Australia↗
PubMed1995

Risky heterosexual practices amongst women over 30: gender, power and long term relationships.

Statistics suggest that older and younger people are about equally at risk for HIV infection, yet existing research on heterosexuality and safer sexual practices has tended to focus on people under the age of 25. The present qualitative study investigates risk behaviours and the practice of safer sex in older populations. Group discussions comprising women over the age of 30 (n = 23) targeted two issues: the gendered power dimension of heterosexuality and safer sex in long term relationships. Cohort issues were also discussed. The discussion groups revealed that the imbalance of power between men and women which has been shown by previous research to constrain younger women's choices with regard to safer sex, continues to affect older women's decisions. Many of the group participants still found it difficult to assert themselves in sexual relationships and even those who were able to challenge overt pressures to engage in unsafe sex were still susceptible to internalized social pressures. In addition, it seems that risks for older age groups are increased by difficulties in continuing to use condoms in long term relationships where monogamy cannot be taken for granted. It was also apparent that there are difficulties in changing sexual behaviours which were established before HIV became an issue.

Adult↗
PubMed1995

Large group community-based parenting programs for families of preschoolers at risk for disruptive behaviour disorders: utilization, cost effectiveness, and outcome.

A significant percentage of children with disruptive behavior disorders do not receive mental health assistance. Utilization is lowest among groups whose children are at greatest risk. To increase the availability, accessibility, and cost efficacy of parent training programs, this prospective randomized trial compared a large group community-based parent training program to a clinic-based individual parent training (PT) programs. All families of junior kindergartners in the Hamilton public and separate school boards were sent a checklist regarding problems at home. Those returning questionnaires above the 90th percentile were block randomly assigned to: (1) a 12-week clinic-based individual parent training (Clinic/Individual), (2) a 12-week community-based large group parent training (Community/Group), or (3) a waiting list control condition. Immigrant families, those using English as a second language, and parents of children with severe behaviour problems were significantly more likely to enroll in Community/Groups than Clinic/Individual PT. Parents in Community/Groups reported greater improvements in behaviour problems at home and better maintenance of these gains at 6-month follow-up. A cost analysis showed that, with groups of 18 families, Community/Groups are more than six times as cost effective as Clinic/Individual programs.

Child Behavior Disorders↗
PubMed1995

Specification, migration and assembly of the somatic cells of the Drosophila gonad.

The adult ovaries and testes contain several specialized somatic cell types that support the differentiation of germ cells into mature gametes. Each of these cell types arise from mesodermal cells that constitute the embryonic gonad. To explore the mechanisms governing the development and differentiation of these cells, we focus on the formation of the gonad during Drosophila development. Using markers for the precursors of the somatic cells of the gonad, we identify discrete steps in the development of the gonad. Our results suggest the existence of different populations of gonadal precursors at early stages in gonadogenesis that represent precursors of cell types found within the adult gonad. The functions of the homeotic genes abdominal A and Abdominal B are required for the development of gonadal precursors, however, here we provide evidence that each plays a distinct role. abd A activity alone specifies anterior gonadal precursor fates, whereas abd A and Abd B act together to specify a posterior subpopulation of gonadal precursors. Once specified, gonadal precursors born within posterior parasegments must move to the site of gonad formation. Here, we show that the proper regional identities, as established by homeotic gene function, are required for the arrest of migration at the correct position. Finally, our analysis of late stages of gonadogenesis suggests that abd A is required in a population of cells within parasegments 10 and 11 that partially ensheath the coalescing gonad. Mutations in iab-4 abolish expression of abd A within these cells, and as a result block the coalescence of the gonad.

Animals↗