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Biomedical subjects

N Byrne

Publications and source records attributed to N Byrne.

At least 19 recordsLinked to original sources
PubMed2003

Symptoms are an important outcome in chronic obstructive pulmonary disease clinical trials: results of a 3-month comparative study using the Breathlessness, Cough and Sputum Scale (BCSS).

The need to manage the key symptoms of chronic obstructive pulmonary disease (COPD) (breathlessness, cough and sputum) is an important treatment objective. Viozan (sibenadet HCl, AR-C68397AA) is a novel dual D2 dopamine receptor, beta2-adrenoceptor agonist, which combines conventional bronchodilatory activity with the sensory nerve modulation afforded by dopamine agonism. The efficacy of this agent in relieving patient symptoms has been determined in a series of large-scale clinical studies; the results of a 3-month, placebo-controlled multi-centre study are reported. Effect on patient symptoms was determined using a novel patient-reported assessment instrument, the Breathlessness, Cough and Sputum Scale (BCSS). Patients with smoking-related COPD were required to complete a 2-week baseline period before being randomized to one of three treatment groups; sibenadet (500 microg three times daily) plus placebo (twice daily); salmeterol (50 microg twice daily) plus placebo (three times daily); placebo (twice daily) plus a second placebo (three times daily). All treatments were delivered via pressurized metered dose inhaler (pMDI) for 12 weeks. From enrolment, patients were required to complete daily diary cards to record symptoms of breathlessness, cough and sputum, medication use and adverse events. The primary outcome measure was the difference between the mean BCSS total score measured over the baseline period and the mean BCSS total score in the final 4 weeks of the treatment period. Secondary measures included assessment of lung function, rescue medication use, exacerbations, health-related quality of life, opinion of efficacy and safety. Although an initial reduction in BCSS total score (indicating symptom improvement) was seen with sibenadet therapy, this effect was not maintained for the study duration. Salmeterol therapy, however, resulted in a sustained reduction in BCSS total score. No notable benefit over placebo was seen in lung function, exacerbations or health-related quality of life with either active treatment. While the results of this study failed to demonstrate sustained efficacy with sibenadet therapy, they do indicate the value of symptom assessment in the clinical evaluation of new drugs for the treatment of COPD.

Administration, Inhalation↗
PubMed2001

Immunological studies of chronic ocular toxoplasmosis: up-regulation of major histocompatibility complex class I and transforming growth factor beta and a protective role for interleukin-6.

A murine model was used to characterize the local immune and inflammatory response during ocular toxoplasmosis. Major histocompatibility complex (MHC) class I, normally expressed at low levels in immune-privileged sites such as the eye, was up-regulated during infection as determined by competitive reverse transcriptase (RT)-PCR and immunocytochemistry for both beta2-microglobulin and the MHC class I heavy chain. However, the eyes of chronically infected mice also had increased levels of mRNA transcripts for transforming growth factor beta, a cytokine associated with immune privilege and constitutively expressed in normal eyes. Transcripts for a number of inflammatory mediators, including interleukin-6 (IL-6), were increased during chronic infection. The role of IL-6 was further investigated by comparing disease progression and the development of the local immune response in wild-type (WT) and IL-6-deficient mice (IL-6(-/-) mice). Following infection, IL-6(-/-) mice developed more severe inflammation in the retina and vitreous humor compared with WT mice. This increased severity of disease was associated with reduced ocular IL-1alpha and increased tumor necrosis factor alpha mRNA production compared with WT mice. Moreover, the increased severity of disease in IL-6(-/-) mice correlated with increased eye parasite burden as determined by RT-PCR for the Toxoplasma gondii bradyzoite-specific LDH2 gene. These results demonstrate alterations to components of immune privilege as a result of ocular toxoplasmosis and a role for IL-6 in controlling parasite numbers and inflammation in the eye.

Animals↗
PubMed2000

Appetitive and consummatory sexual behaviors of female rats in bilevel chambers. II. Patterns of estrus termination following vaginocervical stimulation.

Copulation with intromission or manual vaginocervical stimulation (VCS) shortens the duration that intact female rats maintain lordosis responding during estrus. The present study examined whether VCS could shorten the duration of both appetitive and consummatory measures of female sexual behavior, and whether these effects occur differentially in time and across different hormone priming intervals. Ovariectomized, sexually experienced female rats were administered subcutaneous injections of estradiol benzoate 48 h and progesterone 4 h, before receiving 50 manual VCSs with a lubricated glass rod distributed over 1 h. Control females received sham VCSs distributed over the same time. The females were then tested for sexual behavior in bilevel chambers with two sexually vigorous males (to one ejaculatory series or 10 min with each male, separated by 5 min) 12, 16, and 20 h after VCS. Prior to the final hormone treatment, different groups of females had been given the same hormone treatment either 28, 14, 7, or 4 days before. In females tested at 28- and 14-day hormone intervals, VCS induced both active and passive rejection responses at 12, 16, and 20 h. In contrast, females that received sham VCS displayed relatively normal sexual behavior at 12 h, although by 16 and 20 h these females displayed active and passive rejection. Females tested at 7- or 4-day intervals displayed normal levels of lordosis at all testing times, regardless of VCS treatment. These data indicate that VCS facilitates rejection responses that precede the decrease in lordosis responsiveness. However, the effects of VCS are dependent on the frequency of hormone priming, suggesting that hormone treatment may block some of the long-term inhibitory effects of VCS on female sexual behavior.

Animals↗
PubMed1997

The social contract challenge in medical education.

Medical education has been criticized for loss of touch with the health needs of society. A social contract implies that medical schools, their students and teaching staff have certain rights and privileges in return for serving society. Commitment to this important reciprocal relationship makes it necessary to ensure that medical students gain understanding of the basic health needs of the communities they will serve. Health, Illness and the Community (HIC) is a mandatory course in the first and second years of the curriculum at the University of Toronto. Its goal is to provide students with community learning experiences by involving over 300 community agencies as learning sites. The course takes place one half-day per week throughout first and second year. All 177 students initially work with patients in their homes and in public health units and related agencies. Students are then assigned to agencies using health determinants and health promotion strategies. In the second year, each student selects an agency in the community, and carries out for the entire year a major project focused on the interaction of a health problem with a social issue. This educational initiative has been received well by community agencies and patients. Teaching staff have been enthusiastic and students have performed very well. A major obstacle has been the negative attitudes of some students to community-based learning, but these appear to be improving with time. Involving multiple agencies as learning sites is a feasible method for enabling students to learn about community health needs.

Community Medicine↗
PubMed1996

From feedback to reciprocity. Developing a student-centered approach to course evaluation.

Reforms to medical education have refocused curricula on the need to produce primary care physicians through a problem-based, student-centered, community-oriented, and integrated approach to instruction. Course evaluations, originally designed for traditional lecture-based, teacher-centered curricula, provide inadequate input from students to support curriculum planning and change and to determine appropriate mixes of educational methods. At the University of Toronto Faculty of Medicine, a unique community-centered course, called "Health, Illness and the Community," developed a student-centered course evaluation to provide adequate student input to support curriculum planning and change. A 35-item evaluation was developed to obtain data to identify student concerns, student learning styles, and preferred community agency utilization. The results suggest that student-centered course evaluation can play a role in managing and identifying key relationships in integrated and systematic courses as well as establishing a method for continual improvement.

Curriculum↗
PubMed1994

Plasma from patients with seronegative myasthenia gravis inhibit nAChR responses in the TE671/RD cell line.

Myasthenia gravis (MG) is an autoimmune disorder in which anti-acetylcholine receptor (AChR) antibodies cause muscle weakness. In 10-15% of MG patients anti-AChR antibodies are undetectable (seronegative MG, SMG), though clinical and experimental evidence points to causative circulating factors. Using whole-cell patch-clamp techniques, we investigated the effects of heat-inactivated plasma from SMG patients (n = 7) on voltage-gated sodium [INa(V)] and ACh-induced nicotinic AChR (nAChR) currents in the human rhabdomyosarcoma cell line TE671/RD, comparing the results to those obtained with plasma from healthy individuals (HC, n = 6), patients with Guillain-Barré syndrome (GBS, n = 3) or those with other neurological diseases (OND, n = 3). None of the plasma samples inhibited INa(V). nAChR currents were rapidly (< 1 min) and significantly (P < 0.01) reduced by a 1:10 dilution of plasma from SMG patients compared with plasma from healthy controls and were not restored by washing. The inhibition appeared in some cases to be calcium dependent since for one of three plasmas it was prevented by 10 mM EGTA in the patch pipette. Currents were also reduced by two of three plasmas obtained from GBS patients at 1:3 dilution, but not by the three plasmas from patients with ONDs. The rapid action of plasma from SMG patients argues against an antibody-induced reduction in nAChR numbers; its calcium dependence in one case suggests action by a second messenger that might involve nAChR phosphorylation.

Adolescent↗
PubMed1993

alpha 1-Proteinase inhibitor, elastase activity, and lung disease severity in cystic fibrosis.

The potential role of neutrophil elastase in exacerbating pulmonary infection and tissue damage in cystic fibrosis (CF) has led to proposals for treatment of lung disease in CF with the elastase inhibitor, alpha 1-proteinase inhibitor (alpha 1PI). Reports that alpha 1PI is inactivated in the CF lung suggest that the effectiveness of alpha 1PI therapy depends on the quantity of elastase present and the extent of alpha 1PI inactivation, both of which are expected to vary with disease severity. In this study we assessed the elastase-alpha 1PI profile in sputum and plasma from CF patients with various degrees of pulmonary involvement. Levels of active elastase in sputum samples increased with severity of pulmonary disease (F ratio = 5.63, p < 0.01), as did sputum levels of alpha 1PI (F ratio = 4.88, p < 0.01). A positive correlation was observed between sputum levels of active elastase and alpha 1PI (r = 0.68, p < 0.005). Plasma alpha 1PI levels were also elevated in CF patients compared with control subjects (p < 0.005), indicating a compensatory increase in plasma and sputum levels of alpha 1PI in response to increased elastase load. Molar levels of total immunogenic neutrophil elastase were, on average, 12 times higher than alpha 1PI in CF sputum. These results suggest that the major contributor to the elevated levels of active elastase observed in the CF lung is an increase in elastase release rather than inactivation of alpha 1PI.

Adolescent↗
PubMed1991

Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome)

Neuromyotonia is a rare disorder of unknown cause in which hyperexcitability of peripheral motor nerves leads to incapacitating muscle twitching, cramps, and weakness. We investigated an antibody-mediated mechanism for neuromyotonia in a 24-year-old man with a 7-year history of severe disease unresponsive to pharmacological treatment. Two periods of plasma exchange each produced almost complete disappearance of symptoms for 2-3 weeks, and a highly significant decrease in recorded neuromyotonic discharges. Injection of the patient's plasma or purified IgG into mice significantly enhanced in-vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve-diaphragm preparations. This finding suggests that an increase in neurotransmitter release might result from an antibody-mediated reduction in the number of functional potassium channels that normally regulate nerve excitability. The demonstration of pathogenic IgG autoantibodies in acquired neuromyotonia suggests that immunosuppressive treatment may be helpful in severe cases.

Adolescent↗
PubMed1990

Evaluating ethical sensitivity in medical students: using vignettes as an instrument.

As a preliminary step to beginning to assess the usefulness of clinical vignettes to measure ethical sensitivity in undergraduate medical students, five clinical vignettes with seven to nine ethical issues each were created. The ethical issues in the vignettes were discussed and outlined by an expert panel. One randomly selected vignette was presented to first, second and third year students at the University of Toronto as part of another examination. The students were asked to list the issues presented by the patient problem. Responses from 281 students were obtained. These students identified an average of 2.72 ethical issues per vignette. Each response was classified under the domains of autonomy, beneficence and justice. Comparisons were made between classes and between vignettes. There was considerable variation between classes and the responses to different vignettes seem to indicate that different vignettes measure the various domains in different ways. It does appear that the use of vignettes is one way to measure aspects of ethical sensitivity in medical students but more study is required to clarify exactly what is being measured.

Beneficence↗
PubMed1980

An educational program for psoriatics: an evaluation.

Patients with psoriasis referred to the Dermatology Service at Women's College Hospital and satisfying certain criteria relating to percentage body involvement, age, and the absence of serious coincident conditions were assigned at random to three weeks of day care and education at the Psoriasis Education and Research Centre (PERC) or to the Dermatology Service at Women's College Hospital (WCH) for normal hospital care. On admission, all study patients received normal history and physical examinations and were photographed by a standardized procedure that provided an accurate estimate of type and extent of body involvement. A functional history was taken from PERC patients that provided information concerning their ability to cope at home, at work, and socially; the extent and appropriateness of their self-care practices; and their knowledge concerning the pathophysiology and etiology of psoriasis and the names and actions of the medications they were using. Individualized patient education programs were designed with reference to the medical and functional information and implemented in the three weeks of day care. Photographic assessment and the functional history were repeated at three weeks, six months and twelve months. Hospital patients were reassessed at six and twelve months and a functional history was taken at six months. The functional status of PERC and hospital patients was compared at six months. The results of this study reinforced the belief that in the case of psoriasis, education coupled with treatment is more effective than treatment alone.

Evaluation Studies as Topic↗