<p>Receptors that bind immunoglobulin (Ig) via the Fc domain are known as Fc receptors (FcR). These receptors are integral transmembrane glycoproteins that are expressed on virtually every haematopoietic cell. FcR mediate a wide range of immunological functions from phagocytosis to cellular activation, however, the function and expression of FcR on CD4⁺ T cells is unknown. Thus, in vivo and in vitro studies were undertaken to investigate FcR expression and function on CD4+ T cells.</p> <p>Previously it has been demonstrated that CD4⁺ T cells activated with antigen-pulsed macrophages or interleukin 1 (IL-1) generated IgG and IgA binding factors (IgGBF and IgABF). These immunoglobulin binding factors (IgBF) are one component of a soluble macromolecule, known as a contrasuppressor factor (CSF). These CSF act to augment IgG or IgA responses in vivo and in vitro in an isotype-specific manner. Serological and functional data presented here demonstrate that the IgGBF and IgABF are soluble FcϒRII/III and FcαR, respectively. sFcR could functionally substitute for the IgBF and enhanced antibody responses in an isotype-specific manner. Recombinant sFcϒRIII/III, at concentrations of 0.01 to 0.5 ng/mI could augment IgG PFC responses. However, at higher concentrations (10 to 100 ng/ml) it failed to augment IgG PFC responses. Furthermore, the enhancing activity of the IgBF/sFcR was mediated through a subset of T cells that adhered to the lectin Vicia villosa (Vv T cells). In xid mice, which are unable to generate CSF, T cells could generate the IgBF. However, the xid mice lacked circulating regulatory Ig (reg Ig) that is also necessary for the generation of the CSF, resulting in defective CSF.</p> <p>Since activation of CD4⁺T cells induced the generation of sFcϒRII/III, I investigated FcϒR expression on CD4⁺ T cells utilizing an allogeneic activation system. FACS and PCR data from these studies demonstrated that alloactivation of purified CD4⁺ T cells with CH12.LXB cells induced de novo FcΥRIIBI expression within 24 hours and prior to DNA synthesis. The induction of FcΥRIIBI expression could be blocked by anti-MHC class II mAb, however, direct TCR ligation, even in the presence of IL-2, was not sufficient to induce expression. Moreover, the induction of FcΥRIIBi expression on CD4⁺ T cells was not dependent upon the Ig isotype of the CH12.LX B cells. Alloactivation of CD4⁺ T cells with different isotype-switch variants of the CH12.LX B cell line resulted in significant increases in the number of FcΥRIIB1⁺ CD4⁺ T cells. However, alloactivation with the IgG2b⁺ CH12.LX B cell line induced the largest number of FcΥRIIB1⁺ CD4⁺ T cells. Results from this study indicated that the IgG2b⁺ CH12.LX B cell line secreted a soluble factor(s) that augmented FcΥRIIB1 expression on aIloactivated CD4⁺ T cells. Although, the data suggests that this factor is not soluble IgG2b or IL-1, since both failed to induce FcyRIIBI expression on purified CD4⁺ T cells.</p> <p>In conclusion, these data indicate that alloactivation of CD4⁺T cells induces de novo mRNA and surface expression of FcΥRIIBI within 24 hours and prior to DNA synthesis. In addition, CD4⁺ T cell FcΥRIIBI expression can be augmented by a soluble factor(s) secreted by the IgG2b⁺ CH12.LX B cells. Furthermore, activation of CD4⁺ T cells also induces the generation of sFcΥRII/III and sFcαR. These sFcR participate in the formation of CSF that enhance antibody responses in vivo and in vitro, in an isotype-specific manner, through the activation of Vv T cells.</p> / Doctor of Philosophy (PhD)

<p>This study examines the relationship between neuropsychological functioning and positive versus negative symptoms of schizophrenia in order to test the hypothesis that negative symptoms are uniquely associated with cognitive deficits and attentional impairment. Forty chronic schizophrenics were subtyped on the basis of symptoms which were predominantly positive (n=10), predominantly negative (n=10), both positive and negative (n=10), or neither positive nor negative (n=10) and administered a battery of neuropsychological tests. The possibility that patterns of deficits among subtypes, if found, reflect lateralized or localized dysfunction was also examined.</p> <p>Test data revealed that positive- and negative-symptom schizophrenics are equally impaired according to several global indices of neuropsychological functioning as well as on various measures of attention. These findings are inconsistant with the hypothesis that cognitive and attentional deficits are unique to negative-symptom schizophrenia as has been reported in the literature. Further analysis of deficit patterns revealed that positive-symptom schizophrenics, relative to the asymptomatic group, showed more marked deficits in verbal learning and memory whereas negative-symptom schizophrenics, based on identical comparisons, showed greater impairment on measures of fluency and productivity. No relation was observed between neuropsychological indicies of right versus left or, anterior versus posterior dysfunction and a patient's symptom status. In fact, the low correlation between psychiatric symptoms and neuropsychological performance was generally observed. Reconceptualization regarding defining characteristics of postive- and negative-symptom syndrome, particularly with respoect to assumptions about attention and cognition, is suggested.</p> <p>The heterogeneity of neuropsychological deficits found among schizophrenics and their dissociation from the patients psychiatric presentation, stress the need for independent, individual assessment of cognitive functioning. Given that neuropsychological deficits, when identified, likely contribute to imparied social and occupational functioning, improvement in neuropsychological status may translate into improvement in these areas of everyday living. Preliminary results of an attempt at computer-based cognitive remediation in a seleted subset of schizophrenics are presented and a neuropsychological approach to psychiatric rehabilitation is proposed.</p> / Doctor of Philosophy (PhD)

<p>In the analysis of biomedical data, a question commonly asked by researchers involves the determination of the "best " or "worst" member of a group of results and an associated measure of the probability that this member is the "best" or "worst". Commonly, analysis of variance is suggested as the test of choice. Unfortunately, this test does not exactly answer the original question and further testing must be done to satisfy the question completely. This thesis presents a non-parametric rank test which directly answers the question of "best" or "worst".</p> <p>Before applying this test to biomedical problems, the probability tables associated with this test are expanded and the methods used are presented and discussed. An analogous parametric test is then described and compared in performance with the non-parametric test throughout the remainder of the thesis. Power curves for both the nonparametric and parametric test are developed for several population distributions and the results compared. The three areas of application are; chromosome frequencies in the culture of human melanoma tissue; scoring patterns among evaluators of letters of applications to medical school; and the determination of outliers when relating vital capacity to ventilatory response.</p> <p>It was found that except for cases where the number of objects was less than 10, the parametric test has equal or greater power than the non-parametric test when analysing continuous data, regardless of the population distribution. For less than 10 objects, the non-parametric test had greater power regardless of population distribution. Subsequent to analysis in the three areas cited, it was concluded that the two tests agreed very highly in selecting extreme deviates although the non-parametric, test was consistently more conservative in its probability measure. The problem of ties was found to weaken the power of the non-parametric test as did the ranking procedure itself but its ease of application and superior power with small sample sizes is a distinct advantage. The robustness of the parametric test is obvious throughout the examples. A method of selecting data values which are second or third most extreme was tested and it became obvious that the data must be displayed to show its distributional characteristics before this type of analysis could be carried out or interpreted.</p> / Master of Science (MS)

<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)