<p>This thesis is a report of the analysis of the patient, use and illness characteristics of the visitors of two Hamilton, Ontario emergency departments. Emergency room utilization has increased greatly, in recent years; much of this increase has been due to non-urgent emergency visits. Consequently, in this study characteristics of emergency use and, specifically, non-urgent use were examined.</p> <p>The socio-demographic characteristics of a 1971 random sample of residents of North Hamilton were compared to the 1971 Census to establish the representative nature of this random sample. The emergency department users of the Hamilton General Hospital who reside in North Hamilton were compared to the random sample of residents. The emergency department users were characterized as being male, non-single, Protestants, native Canadians, less educated and of lower social class. The users were separated into two groups by urgency classification (emergency-urgent 52%; non-urgent 48%) and compared with the sample of residents. Non-urgent users were characterized as being younger and as having less residential tenure both in Hamilton and at their present address than residents in general. No characteristics differentiated the emergency-urgent users from residents. A younger age profile was the only socio-demographic characteristic which differentiated the two groups of urgency status. Four of the 16 illness variables separated these two groups: the emergency-urgent users were more likely to have been involved in an accident, suffered trauma, arrived by ambulance and preferred are at the emergency department.</p> <p>The users of the emergency department at St. Joseph's Hospital who also resided in North Hamilton were compared with the users from the Hamilton General. The St. Joseph's users were more likely to be younger, single, and Catholic than the users of the General. Although the General users were more likely to have suffered trauma, they were less likely to be classified as emergency-urgent than the users at St. Joseph's Hospital.</p> <p>The roles that the two emergency departments play for the residents of North Hamilton are analyzed. Although both serve as acute care, trauma centres, the General is functioning relatively more as a physician surrogate for some North Hamilton residents. Accessibility and availability of alternate primary care services are discussed for the non-urgent patient. Recommendations are offered to alleviate the demand placed on the emergency department by those most effected by its physician surrogate role.</p> / Master of Science (MS)

<p>Since the pioneering work of Pickles et al . (1965), prostanoids have been implicated in the pain and discomfort of primary dysmenorrhea. Accordingly, current pharmacotherapy is based on the inhibition of prostanoid synthesis. However, 10% to 25% of women who suffer from primary dysmenorrhea fail to gain relief from such therapy. The development of alternative therapies to treat these women has been hindered by the fact that the effects of prostanoids on human nonpregnant myometrium have not been quantified in a rigorous way. The prostanoid thromboxane A2 , causes vascular smooth muscle contraction by interacting with specific prostanoid receptors known as TP receptors, the nomenclature follows recent International Union of Pharmacology recommendations where each prostanoid receptor is designated by the letter P, preceded by a letter signifying the most potent natural prostanoid agonist at that receptor. At the time my thesis was undertaken, several observations suggested that the TP receptor may be involved in the physiological and pathophysiological control of myometrial contractility. Therefore, the purpose of this study was to thoroughly characterize the TP receptor population in human nonpregnant myometrium. I evaluated the pharmacological characteristics of the myometrial TP receptor via in vitro functional and radioligand binding studies and employed reverse transcription-polymerase chain reaction assays to evaluate TP receptor mRNA expression. Both U-46,619 and I-BOP produced concentration-dependent contraction of human myometrial strips in vitro (p EC50 = 6.9 ± 0.27; and 7.8 ±0.60, respectively). The contractile activity induced by U-46,619 was attenuated by seven selective TP receptor antagonists. Lastly, the sensitivity of human nonpregnant myometrium was not regulated by anatomical location, tissue orientation or menstrual cycle status of the donor. The binding of [125 I]-BOP to human myometrial membranes was saturable, selective and displaceable. Equilibrium binding of [125 I]-BOP identified one class of sites, Kd = 3.4 nM (pKd = 8.7 ± 0.4) and a maximum binding of 323.1 ± 361.5 fmol/mg protein. The addition of the non-hydrolyzable GTP analog GTPγS (100 μM), to the assay had no effect on [125 I]-BOP binding. The rank order of potency for the seven TP receptor antagonists in displacing [125 I]-Bop from its binding site was correlated (r = 0.75) with the rank order of potency in inhibiting U-46,619-induced contraction of myometrial strips. Ligands selective for other prostanoid receptors were unable to significantly displace [ 125 I]-BOP binding. A novel qualitative RT-PCR methodology was developed and with this technique TP receptor mRNA expression was demonstrated in human nonpregnant myometrium excised from different uterine locations, from donors in both the proliferative and secretory phases of the menstrual cycle. The basis for a semi-quantitative RT-PCR methodology was established and an examination of potential influences on TP receptor mRNA expression, such as tissue excision site and donor menstrual cycle status, was begun. Lastly, the semi-quantitative data describing the amplification of TP receptor mRNA was highly variable, however the factor(s) responsible for such high variability remain to be determined. All taken together, these results suggest that a single homogeneous population of TP receptors, most closely resembling the putative low affinity TP receptor population in human platelets, resides in human nonpregnant myometrium.</p> / Doctor of Philosophy (PhD)

<p>Telephone support is an intervention that is capable of delivering information, education, and psychosocial support to informal caregivers of persons with dementia. However, there has been very little research published examining the intervention of telephone support and its effect on the caregiving experience. A critical review of the literature revealed little information about the dimensions of telephone support and the experiences of those who receive and provide this intervention. Qualitative research is needed to achieve an enhanced understanding of telephone support services, and to understand the perspectives of those involved in this service. This thesis describes a qualitative case study seeking to understand the intervention of telephone support for caregivers of persons with dementia. In-depth interviews were conducted with eight dementia caregivers and four telephone support providers. The dimensions of telephone support identified were information, referral, emotional support, and convenience. The experiences of caregivers with this intervention revealed the sense of companionship offered through telephone support. The experiences of the providers revealed telephone support as a means to assist and empower caregivers to meet their needs for information, referral, and emotional support. The professionals also described some of the frustrations experienced when providing this form of support. After interpreting the data on the dimensions of the caregiving experience and the intervention of telephone support, it was evident how such an intervention can impact the dementia caregiving experience. Not only does telephone support conveniently meet the needs of caregivers, but it helps to minimize negative outcomes such as loneliness and role isolation, and helps foster positive outcomes such as mastery and self esteem. This new knowledge has implications for the planning and delivery of telephone support that will meet the individualized needs of caregivers of persons with dementia.</p> / Doctor of Philosophy (PhD)

<p>The manner by which a person walks provides information about the functioning of the nervous system. Information of this type may be useful in the determination of the etiology(s) and management of autism. The primary purpose of this pilot study was to determine whether a difference existed between a group of four adolescent males with autism and a group of three normal male adolescents in 17 parameters of gait studied. A secondary purpose of the inquiry was to test a method of collecting and extracting data on temporal-spacial, linear, angular and qualitative gait parameters through the use of a videotaping/data extraction technique. Markers were placed on specific sites on the subjects' body to enable the measurement of joint angles. The subjects were then video taped while they walked up and down a walkway for a total of six times. Data was extracted from the videotape for 15 of the parameters studied. A footprint paper technique was used to collect data on two gait parameters. All data was extracted from the videotape by the investigator. In order to assess a sample of the intrarater reliability of the outcome measures, the investigator extracted data for two of the gait parameters studied on two occasions. Results indicate that the intrarater reliability was excellent for the sample of outcomes measured. Student t-test and chi square analysis revealled no statistically significant differences between the two groups in the 17 gait parameters studied. Clinical significance was found for the knee angle in the initial contact position, alternate arm swing and head position parameters. A Repeated Measures Analysis of Variance (1 factor) analysis showed no significant differences between the two study groups in the symmetry of right and left leg gait parameters. However, the likelihood of detecting a difference should one have existed, is limited due to the small sample size and the limitations and biases operative in study. Therefore, no definitive conclusion can be drawn concerning the differences in the gaits of the groups studied. Modifications to this study are suggested which may enable future research to answer the study question.</p> / Master of Health Sciences (MSc)

<p>The issues in providing adequate health care for rural populations in developing countries and Sierra Leone in particular are discussed - showing the need for a community-based health care programme to counteract the problems not being addressed by institutionalized health care services.</p> <p>The literature has been reviewed to assess the methods-whereby community health programmes using village workers or village groups have been used around the world.</p> <p>A randomized controlled trial has been designed to test the effectiveness of one particular health status of rural people in Sierra Leone. It is hoped that the results of this study will enable the Sierra Leone government to decide on a national primary health care programme for use in Sierra Leone.</p> / Master of Science (MS)

<p>The issues relating to planning for health care delivery in developing countries, the current health care delivery system in rural Sierra Leone and the health care problem of this rural population particularly infant and children, have been examined. The research literature was reviewed and the various options for health care delivery systems to rural communities were discussed.</p> <p>A design for a randomized controlled study to evaluate the effectiveness of health care teams led by medical assistants working in pairs in reducing infant and childhood mortality and malnutrition and improving sanitation and safe water supplies of communities will be compared with effectiveness of health care teams led by nurse dispensers working in pairs and individually, has been presented. The proposed study is intended to be carried out in nine chiefdoms in rural Sierra Leone and it is expected to last for 52 months.</p> <p>It is anticipated that the result of the study will provide information useful to the Ministry of Health in Sierra Leone to plan for a future health care delivery system in rural Sierra Leone.</p> / Master of Science (MS)

<p>Quality of care in the Emergency Department may be influenced by several factors and Canada is in the process of training specialists in Emergency Medicine to improve and standardize emergency care. Emergency departments are increasingly used and medical staff and in the organization there is a wide variation in the of the departments. This proposal describes a design for a multi-centre cohort to answer the question: "Is there any difference in the quality of care provided in Ontario's Emergency Department (ED) by Emergency Room Physicians (EP), Casualty Officers (CO) and General Practioners (GP)?". The study is confined to 35 eligible hospitals, within 100 Km around Hamilton, with more than 300 beds, with an average visit in the ED of more than 100 visits/day, with full time medical coverage, supporting facilities and access to specialized consultations. Twenty-eight physicians will be selected randomly in each of the 3 physician categories, half of them will be in university affiliated hospitals. The outcome measure is the assessment of quality of care: 1) the "technical process" of care will be assessed using ten indicator conditions and the data will be collected by unobtrusive observation and chart review; 2) the "art of care" will be assessed by the ED nurse observer; 3) the "patient outcome" will be assessed two weeks after the ED visit by a phone interview done by a research assistant. Each physician will be observed during two shifts. Each case will be classified as urgent or non-urgent. More than 6 cases per physician need to be assessed to detect a 25% difference between the groups with a risk alpha of 1% (two tailed) and a risk beta of 5%. An analysis of variance will be used to detect a difference for the process score, the physician attitude score and the outcome score. The influence of six factors will be estimated with a multiple regression linear model: 1) university affiliation, 2) urgency of cases, 3) workload, 4) training level of physicians, 5) method of payment and 6) working hours in the ED. Also descriptive data on the structure of the ED will be studied. Thirteen months should permit the completion of the study.</p> / Master of Science (MS)

<p>After specific causes of chronic insomnia have been ruled out (e.g., noctural myoclonus, drug abuse), there remain in a substantial number of patients who have been inexplicably sleepless and fatigued for many years. We wished to learn whether the chronicity of insomnia in these patients was associated with phase-shifts in circadian rhythm, a disorder of internal timekeeping. We identified three types in a pilot study: 1) phase-delay, b) phase-advance, and c) an arrhythmic group.</p> <p>Delayed sleep-phase insomnia (DSPI) has been well described. It is characterized by an intractably late sleep-onset and awakening time, a consistent sleep time-frame, and an essentially normal sleep EEG.</p> <p>Advance sleep-phase insomnia (ASPI) is a much rarer phenomenon, with few reported cases. Sleepiness becomes overpowering in the late afternoon or early evening, followed by a very short sleep onset latency and exceedingly early awakening time. The EEG is essentially normal.</p> <p>Amplitude disorders and arrythmia are even more rare under normal environmental conditions. They have been described but not carefully examined. We identified two patients in the pilot study who displayed a complete arrythmia of their core temperature cycle. Their sleep was marked by variable onset latencies, and severe difficulties with sleep maintenance. Sleep-time averaged less than two hours per night, and was associated with a substantial reduction in the slow-wave sleep.</p> <p>Though these patterns sound easy to recognize, they are often obscured in patient reports. For example, social schedules requiring early rising for work in spite of phase-delay or explanations that patients develop to better account for their predicament may disguise true patterns. We tried to detect the more intractable features in patient histories and reported patterns of sleep and to predict which type of phase disturbance each might have.</p> <p>The physiological aspects of the circadian phase disturbance was examined using the sleep-wake cycle (14 x 24 hours), core body temperature (5 x 24 hours), serum cortisol (1 x 24 hours) and serum melatonin (1 x 24 hours) as circadian parameters. Monitoring was carried-out on three patient groups identified in the Sleep Disorders Clinic as being : 1) phase-delayed, 2) phase advanced, or 3) arrythmic.</p> <p>The phase-delay group showed a significant delay in the acrophase of core temperature rhythm, but not serum cortisol. The phase advance group showed a significant advance in the acrophase of both rhythm parameters. The arrhythmic group displayed a highly variable core temperature acrophase but intact 24 hour waveforms. Serum cortisol had no discernable rhythmic component in this group.</p> <p>The circadian rhythm of serum melatonin showed a significant acrophase delay for all patient groups. This was an unexpected result, as the phase control of melatonin secretion is thought to originate from oscillators providing phase information to the other parameters meausred in this study.</p> <p>Also important was the finding that there was no significant difference in the amplitude or period length for all three circadian rhythm parameters. Thus, "phase-disorders" seen in the present study possibly represent a defect in carcadian rhythm timing but not in the generation of rhythms themselves. However, in patient Group 3 the substantial increased point to point random variation in core temperature and the arrhythmic nature of the serum cortisol secretion could imply involvement of rhythm timing and/or generation.</p> <p>Since these phase disorders were associated with a consistent and unidirectional phase change in the circadian pattern of melatonin secretion, it is hypothesized that the pathology in these patients may lie at the level of the suprachiasmatic nucleus. Hyposensitivity to light could interfere with melatonin "offset" signals, while allowing other pacemakers to move toward their endogenous cycling frequencies. Thus, phase delayed, or advanced, or a more drastic rhythm anomaly might ensue.</p> <p>This study also indicates that it may be possible to identify each of the three types of rhythm disturbance on the basis of clinical features that can be obtained by interview. The most important aspects appear to be: 1) chronicity of symptoms, 2) consistency of symptoms, 3) pattern of symptoms, 4) psychiatric and medical histories, and 5) recnet drug histories. In addition, polysomnographic studies are required to exclude specific disorders such as nocturnal myoclonus.</p> <p>Exogenous melatonin administration was carried out on this patient sample. A double-blind, placebo-controlled, 14-day trial showed a significant improvement of both total sleep time and day-time alertness with a 75mg oral does of melatonin as compared to placebo. This is the first study to demonstrate significant clinical soporiphic effects of exogenous melatonin in chronic insomniac patients.</p> / Doctor of Philosophy (PhD)

<p>Evidence from the literature suggests that a limiting factor to the performance of exhaustive exercise is the ability of the brain to maintain the stimulation of the alpha-motor neuron. This these examined the hypothesis that this "central fatigue" results from a deficit in the transfer of information across striatal dopaminergic synapses. Decreases in striatal dopaminergic activity should impair exercise capacity whereas increases in dopaminergic activity should therefor improve exercise capacity. The rat was chosen as the experimental animal because of the availability of techniques to alter dopaminergic activity and to quantify exercise capacity. Striatal dopaminergic activity was reduced by depletion of striatal dopamine by an intracerebroventricular injection of 200mg of 6-hydroxydopamine. Dopaminergic activity was increases by an intreperitoneal injection of the specific dopamine receptor agonist apormorphine. Exercise capacity was quantified with treadmill-grid system by measuring the time taken for a running rat to become exhausted. Striatal dopamine depletion decreased exercise capacity whereas apomorphine increased xercise capacity. In contras, striatal and hpothalmic norepinephrine depletion had no effect on exercise capacity.</p> <p>The limitation of exercise capacity by the activity of striatal dopaoinergic synapses was not due to a failure of these synapses to maintain the release of dopamine, but may be due to these synapses releasing amounts of dopamine which are insufficient to transmit all the information arriving at the presynaptic terminal to the postsynaptic neuron. I propose that the release of dopamine is limited in exhausted rats by the activitation of presynaptic dopamine receptors located on the terminal and that the purpose of these receptors is to maintain the concentration of dopamine in the functional pool of the terminal.</p> / Doctor of Philosophy (PhD)

<p>This thesis examined developmental changes in morphology of the GnRH neuron in the female rabbit brain during sexual maturation. In the adult virgin rabbit approximately 1,000 GnRH cells were counted in half the hypothalamus. Two morphologically distinct populations of GnRH neurons were found. Fusiform cells with relatively smooth contours (smooth) accounted for 34% of the total. Cells with irregular contours (rough) represented 64% of the immunoreactive cells counted. In a subsequent experiment GnRH cell types were quantified in rabbits treated with Tamoxifen (TAM, 10 mg/kg/day), vehicle, and pregnant mare serum (PMS, 50 IU on postnatal days (PND) 25 and 28). Sexual maturity was considered achieved when rabbits attained a body weight of 3.0 kg. The proportion of rough cells increased while the smooth cells decreased with sexual maturation. This change was advanced by PHS treatment and prevented by TAM treatment compared to controls. Sexual maturity was advanced by PMS treatment (92 PND) versus controls (108 PND) and delayed by TAM treatment (128 PND). Mean plasma estradiol was significantly (P= 0.01) elevated in PHS rabbits versus controls between PND 25 and 34 and again at PND 75 (p= 0.05). Since the total number of immunoreactive cells remained constant, it is concluded that smooth cells are transformed to rough cells. In another experiment chronic ovariectomy did not change the total number of GnRH cells counted when compared to sham operated rabbits. However, the developmental shift of smooth cells to rough cells was prevented (p<0.05) in ovariectomized rabbits. These results suggest that the developmental change in GnRH cell morphology is functionally related to puberty onset. Moreover, estradiol seems to induce these changes through indirect mechanisms. It is proposed that estradiol augments the growth neural imputs to GnRH cells.</p> / Doctor of Philosophy (PhD)