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Biomedical subjects

M O'Toole

Publications and source records attributed to M O'Toole.

At least 19 recordsLinked to original sources
PubMed2004

Sending children home on tracheostomy dependent ventilation: pitfalls and outcomes.

In spite of the consistency of the primary discharge coordinator in our practice and attempts to streamline the process, the obstacles to discharge highlighted five years ago remain frustratingly similar. The children in this survey spent an average of 9.6 months extra time in hospital awaiting discharge at considerable cost to the local commissioning teams, quite apart from the emotional cost to the child and stress for the whole family. We hope in future years this review will enable health practitioners and local health providers to anticipate the hurdles, address the problems early, and expedite the process of discharging home children who are dependent on long term ventilation via tracheostomy.

Adolescent↗
PubMed2002

Health Opportunities with Physical Exercise (HOPE): social contextual interventions to reduce sedentary behavior in urban settings.

Physical activity interventions targeting social and physical environments of the urban poor hold promise in improving health outcomes in underserved communities. This study randomly assigned overweight, sedentary, economically disadvantaged adults to one of three intervention conditions at The Hope and Healing Center, a large inner-city health facility providing numerous options for exercise. Within the tenets of Social Action Theory, the Health Opportunities with Physical Exercise (HOPE) trial will test the efficacy of two behavior change models, social support and patient-provider interaction, to increase physical activity. In addition to a standard care condition, in which patients have open access to Hope and Healing physical activity programming, patients were assigned to one of two behavior change interventions. Those assigned to patient-peer receive face-to-face, systematic and scheduled encouragement from study-trained 'peer' interventionists at the facility. Patients assigned to patient-provider receive face-to-face, systematic and scheduled encouragement provided by study-trained 'provider' interventionists also at the facility. The primary outcomes of change in exercise behavior will be documented by self-reported physical activity and confirmed by fitness testing at baseline, 6, 12 and 24 months during the 1 year of active intervention and 1 year of relapse prevention follow-up. Intervention conditions will be compared on psychosocial mediators including motivational appraisals, ratings of social support, rapport, problem solving and self-efficacy for overcoming barriers to increased physical activity. Novel aspects of this intervention include: (1) delivery of socially based physical activity interventions to an economically disadvantaged urban population, (2) reduction of environmental barriers to be physically active and (3) emphasis on social interactions influencing health habit change. Results of this study have the potential to identify mechanisms of behavior change that could be adopted by physical activity interventions aimed at reducing sedentary behavior and health disparities in high-risk, underserved populations.

Exercise↗
PubMed2001

Gender differences in exercise-induced changes in sex hormone levels and lipid peroxidation in athletes participating in the Hawaii Ironman triathlon. Ginsburg-gender and exercise-induced lipid peroxidation.

BACKGROUND: Exercise reduces the risk of coronary heart disease in men and women but paradoxically, may promote free-radical formation, lipid peroxidation and vascular tissue injury. In this study, we assessed whether exercise-induced oxidative stress similarly affected men and women who participated in the Hawaii Ironman triathlon. METHODS AND RESULTS: Fifty-seven athletes (38 males) who completed the triathlon (3.9 km swim, 180.2 km bike, 42.2 km run) participated in this study. Blood samples were obtained 2 days before and immediately after the triathlon for the measurement of lipids, antioxidants and sex hormones and for the assessment of the susceptibility of plasma lipids to peroxidation. Lipid changes after exercise were similar for men and women. However, the susceptibility of plasma lipids to peroxidation was reduced by 61% (P < 0.001) in men and only 14% (P = NS) in women postrace. These changes were not associated with the supplemental use or levels of antioxidants. In addition, in men there was an increase of 58% in the antioxidant sex hormone estradiol and a decrease of 58% in testosterone (P < 0.001) postrace. No significant changes were noted for these two hormones in women. CONCLUSIONS: There are significant gender-specific differences in the susceptibility of lipids to peroxidation and in changes in estradiol and testosterone levels as a result of ultra-endurance exercise. These changes may in part explain the salutary effect of exercise on the development of vascular disease.

Adult↗
PubMed2001

Discharge planning for complex paediatric cases.

The aim of this study was to identify the functions performed by social workers specifically engaged in paediatric discharge planning by undertaking a detailed analysis of discharge planning practice in forty cases referred to a specialist discharge planning team, at the Royal Children's Hospital, Melborne. A second aim was to identify the characteristics that distinguished complex cases from more routine cases. Discharge planning activity focused on the family, community and the organisation, with most cases requiring activity in all three areas. More complex cases were characterised by amount of social work time spent on the case, length of stay and number of discharge planner functions performed, but not number of prior admissions.

Child↗
PubMed2000

Neonatal administration of IL-12 enhances the protective efficacy of antiviral vaccines.

Neonates are highly susceptible to infectious agents and are known to display polarized expression of Th2-like cytokines and Abs. This neonatal immune bias has important implications for the development of vaccine strategies, particularly against viral infections. We now report that coadministration of IL-12 and an influenza subunit vaccine at birth enhances the protective efficacy of antiviral vaccination. Immunization and treatment with IL-12 within 24 h of birth resulted in elevated expression of IFN-gamma, IL-10, and IL-15 mRNA in the spleens of newborn mice compared with animals exposed to vaccine only. In addition, these animals showed dramatic increases in IFN-gamma-, IL-2-, and IL-4-secreting cells, and in IgG2a Ab levels upon adult challenge compared with mice primed with vaccine alone. Most importantly, animals vaccinated and simultaneously treated with IL-12 at birth displayed enhanced survival after lethal challenge with infectious influenza virus as adults compared with infected animals that had been primed with vaccine alone. This augmented protection required B cells and could be transferred to naive mice by immune serum. Collectively, these results provide evidence that administration of IL-12 to neonates induces a Th1-like response in newborns and elicits protective antiviral immune memory.

Adjuvants, Immunologic↗
PubMed2000

A CTL assay requiring only 150 microliter of mouse blood.

In this paper, we present a method for measuring antigen specific cytotoxic T lymphocyte (CTL) activity from individual mouse peripheral blood samples without animal sacrifice. Peripheral blood cells are stimulated in vitro with a cocktail of antigen, cytokines, costimulatory molecules and irradiated feeder cells resulting, 7 days later, in a readily detectable antigen specific signal from a well plated under limiting dilution conditions. This highly sensitive and antigen specific assay is more efficient than conventional CTL assays and thus increases the number of mice that can be tested in a single assay. Since blood samples can be assayed from an individual mouse at multiple times during the course of an in vivo study, the assay can facilitate and strengthen correlative studies on CTL responses and in vivo results.

Amino Acid Sequence↗
PubMed2000

IL-12-Dependent enhancement of CTL response to weak class I-restricted peptide immunogens requires coimmunization with T helper cell immunogens.

The effect of in vivo administration of rmIL-12 on the CTL response to immunization with a weakly immunogenic class I-restricted peptide emulsified in incomplete Freund's adjuvant was investigated. In the absence of IL-12, peptide-specific CTL responses were significantly greater following coimmunization with class I-restricted peptide and T helper cell antigens than following immunization with the class I-restricted peptide alone. IL-12-dependent enhancement of the CTL response to peptide immunization was demonstrated in the presence of, but not in the absence of, coimmunization with T helper cell antigen. These findings indicate that IL-12 enhancement of the CTL response to weak class I-restricted immunogens is T helper cell dependent. Treatment with rmIL-12 also enhanced the CTL response to immunization with cDNA encoding both CTL and T helper cell epitopes. These findings are relevant to the design of vaccines containing tumor-associated class I-restricted peptides currently being tested as an immunotherapy for cancer patients.

Animals↗
PubMed2000

Imaging spectrum of breast implant complications: mammography, ultrasound, and magnetic resonance imaging.

Knowledge of the various complications resulting from breast implants and the ways in which they can present radiographically is useful so that a complete evaluation can be made, thus, increasing the accuracy of diagnosis. In this article, a working knowledge of the more common breast implant types, essential to the accurate interpretation of breast implant imaging studies, is presented. In addition, imaging techniques and normal appearances of breast prostheses are described by using mammographic, sonographic, and magnetic resonance (MR) imaging. The findings of breast implant complications by using these modalities are described, including rupture, silicone extravasation, gel bleed, polyurethane breakdown, and peri-implant fluid collections.

Breast Implants↗
PubMed2000

Dose-dependent and schedule-dependent effects of interleukin-12 on antigen-specific CD8 responses.

Interleukin-12 (IL-12) has been shown to play a central role in the innate and acquired immune responses. Its activities include enhancement of natural killer (NK) and cytotoxic T lymphocyte (CTL) activity and promotion of CD4 Th1 cell development. It has also been shown to provide potent activity as a vaccine adjuvant in generating antibody and T cell responses. We have investigated the efficacy of IL-12 protein in promoting CD8 T cell responses when it is used as an adjuvant for immunization. Studies using, as antigen, cDNA from an autologous antigen (P1A) as well as studies of responses to vaccinia virus-delivered self (gp100) and non-self (beta-galactosidase) antigens show that the dose and schedule of IL-12 administration can significantly affect adjuvant activity, leading to enhancement or suppression of antigen-specific responses.

Adjuvants, Immunologic↗
PubMed1999

Potent activity of soluble B7-IgG fusion proteins in therapy of established tumors and as vaccine adjuvant.

Fusion proteins consisting of the extracellular region of murine B7.1 or B7.2 and the Fc portion of murine IgG2a (B7-IgG) were evaluated for their ability to promote antitumor responses. Therapeutic administration of soluble B7-IgG in mice with established tumors induced complete regression of the tumor and increased the survival of mice. In three models, MethA, P815, and MB49, mice with 7-day-old established tumors were cured with two to three treatment cycles of B7-IgG, given twice a week. Even in mice with an established B16/F10 tumor (a poorly immunogenic melanoma), therapeutic treatment with B7-IgG alone slowed tumor growth and increased survival significantly. Still stronger antitumor activity was achieved when B7-IgG was used as a vaccine adjuvant mixed with irradiated tumor cells. In 80% of mice with 7-day-old B16 tumors, tumors regressed completely, and mice survived for at least 80 days. In all tumor models, B7.1-IgG and B7.2-IgG had similar antitumor activity. B7-IgG-mediated tumor rejection was dependent on T cells, specifically CD8 cells, as demonstrated by the failure of B7-IgG to induce tumor regression in severe combined immunodeficient or CD8-depleted mice. In addition, mice that were cured of an established tumor were protected against a rechallenge with the same tumor for at least 4 months, suggesting the generation of memory responses. Surprisingly, the antitumor activity of B7-IgG was independent of IFN-gamma, as demonstrated by tumor rejection in IFN-gamma knockout mice. Our findings demonstrate the potent capacity of B7-IgG to generate or enhance antitumor immune responses and suggest the clinical value of B7-IgG.

Adjuvants, Immunologic↗
PubMed1999

Prediction of sustained ventricular tachycardia inducible by programmed stimulation in patients with coronary artery disease. Utility of clinical variables.

BACKGROUND: Cardiologists often use clinical variables to determine the need for electrophysiological studies to stratify patients for risk of sudden death. It is not clear whether this is rational in patients with coronary artery disease, left ventricular dysfunction, and nonsustained ventricular tachycardia. METHODS AND RESULTS: We analyzed the first 1721 patients enrolled in the Multicenter UnSustained Tachycardia Trial to determine whether clinical variables could predict which patients would have inducible sustained monomorphic ventricular tachycardia. The rate of inducibility of sustained ventricular tachycardia was significantly higher in patients with a history of myocardial infarction and in men compared with women. There was a progressively increased rate of inducibility with increasing numbers of diseased coronary arteries. There was a significantly lower rate of inducibility in patients with prior coronary artery bypass surgery and in patients who also had noncoronary cardiac disease. The rate of inducibility was higher in patients of white race, patients with recent (</=6 weeks) angina, left ventricular dyskinesis, and in patients with greater numbers of fixed thallium defects. Inducibility was more likely in patients who had a prior myocardial infarction complicated by congestive heart failure, ventricular tachycardia, or fibrillation </=48 hours after the onset of infarction. Although these associations are statistically significant, the accuracy of the clinical variables in discriminating between patients with and those without inducible ventricular tachycardia is only modest (receiver operator characteristic area <0.70). CONCLUSIONS: Multiple clinical variables are independently associated with inducible sustained ventricular tachycardia. However, they have limited utility to guide clinical decisions regarding the use of electrophysiological testing for risk stratification in this patient population.

Aged↗
PubMed1999

Cardiac troponin T and I, echocardiographic [correction of electrocardiographic] wall motion analyses, and ejection fractions in athletes participating in the Hawaii Ironman Triathlon.

Cardiac troponin T (cTnT) and troponin I (cTnI) are highly sensitive and specific for detecting myocardial damage even in the presence of skeletal muscle injury. In this study, we assessed whether ultraendurance exercise induced cardiomyocyte injury using plasma cTnT and cTnI measurements, quantitative echocardiographic wall-motion analysis, and ejection fraction measurement in athletes who participated in the Hawaii Ironman Triathlon. Twenty-three athletes (11 men) who completed the triathlon (3.9 km swim, 180.2 km bike, and 42.2 km run) participated in this study. Blood samples were obtained 2 days before and immediately after the triathlon for the determination of cTnT (Enzymun, Roche Diagnostics) and cTnI (Dade Behring) concentrations. Quantitative echocardiographic wall motion analysis and ejection fraction were obtained on 12 of the 23 participants before and immediately after the race. No subject had detectable cTnT or cTnI or abnormal echo score before the race. Following the race, 2 subjects (9%) had marked increases in both cTnT (0.15 and 0.33 microg/L) and cTnI (2.09 and 4.44 microg/L). Four additional subjects (17%) had moderate increases in cTnT (0.04 to 0.05 microg/L) but no detectable cTnI. Race time correlated inversely with cTnT (r = -0.65, p <0.01). Mean change in the number of abnormal echo segments after the race was 6.5 in those with a marked increase in cTnT and cTnI, 2.3 in those with a moderate increase in cTnT, and 1.7 in those with no increase. Ejection fraction decreased by an average of 24% after the race (p <0.002). Thus, ultraendurance exercise may cause myocardial damage as indicated by biochemical cardiac-specific markers and echocardiography. The cellular nature of this damage and whether it is transient or permanent is unclear at present.

Adult↗
PubMed1999

Current status of long term ventilation of children in the United Kingdom: questionnaire survey.

OBJECTIVES: To identify the number and current location of children, aged 0 to 16 years, requiring long term ventilation in the United Kingdom, and to establish their underlying diagnoses and ventilatory needs. DESIGN: Postal questionnaires sent to consultant respiratory paediatricians and all lead clinicians of intensive care and special care baby units in the United Kingdom. SUBJECTS: All children in the United Kingdom who, when medically stable, continue to need a mechanical aid for breathing. RESULTS: 141 children requiring long term ventilation were identified from the initial questionnaire. Detailed information was then obtained on 136 children from 30 units. Thirty three children (24%) required continuous positive pressure ventilation by tracheostomy over 24 hours, and 103 received ventilation when asleep by a non-invasive mask (n=62; 46%), tracheostomy (n=32; 24%), or negative pressure ventilation (n=9; 7%). Underlying conditions included neuromuscular disease (n=62; 46%), congenital central hypoventilation syndrome (n=18; 13%), spinal injury (n=16; 12%), craniofacial syndromes (n=9; 7%), bronchopulmonary dysplasia (n=6; 4%), and others (n=25; 18%). 93 children were cared for at home. 43 children remained in hospital because of home circumstances, inadequate funding, or lack of provision of home carers. 96 children were of school age and 43 were attending mainstream school. CONCLUSIONS: A significant increase in the number of children requiring long term ventilation in the United Kingdom has occurred over the past decade. Contributing factors include improved technology, developments in paediatric non-invasive ventilatory support, and a change in attitude towards home care. Successful discharge home and return to school is occurring even for severely disabled patients. Funding and home carers are common obstacles to discharge.

Adolescent↗
PubMed1999

Immune response enhancement by in vivo administration of B7.2Ig, a soluble costimulatory protein.

The identification of both class I- and class II-restricted tumor-associated peptides recognized by T cells has led to the test of these peptides as immunogens in experimental immunotherapy for cancer patients. However, optimal T cell activation requires signaling both through the T cell receptor for antigen and through costimulatory pathways. B7.1 and B7.2 are powerful costimulatory molecules expressed on the surface of antigen-presenting cells. Using a mouse model, we have sought to optimize costimulatory signals during antipeptide responses by administering a soluble form of B7.2 at the time of peptide immunization. Administration of B7. 2Ig fusion protein significantly enhanced T helper cell and CTL responses. These findings suggest that soluble forms of human B7.2 protein may provide a straightforward and practical method of supplying optimal costimulation during clinical immunotherapy.

Animals↗
PubMed1999

Intranasal interleukin-12 is a powerful adjuvant for protective mucosal immunity.

The use of interleukin (IL)-12 as a new vaccine adjuvant for stimulating protective antiviral mucosal immunity has been examined. Mice were immunized intranasally (in) with an influenza vaccine consisting of soluble hemagglutinin (H1) and neuraminidase (N1) plus IL-12. This treatment resulted in elevated levels of lung and splenic interferon-gamma and IL-10 mRNA. Total and IgG2a anti-H1N1 antibody levels in serum were significantly elevated, as were total, IgG1, IgG2a, and secretory IgA antibody levels in bronchoalveolar lavage (BAL) fluids compared with animals receiving vaccine alone. Mice immunized in with vaccine and IL-12 also exhibited decreased weight loss and dramatically enhanced survival after lethal challenge with infectious influenza virus. Protection was dependent upon the presence of B cells and could be transferred to naive mice by inoculation of either serum or BAL fluid from IL-12-treated mice. These findings show for the first time that soluble IL-12 delivered in serves as a powerful respiratory adjuvant for protective antiviral immunity.

Adjuvants, Immunologic↗