<p>The current method presently in use for diagnosing male asymptomatic urethral gonococcal carrier is considered unsuitable for screening purposes in Sierra Leone. A search for a reliable, cheap, simple, and unobtrusive method found the first voided urine (FVU) as a specimen for culture to be the most promising. Because of methodologic weaknesses associated with previous evaluation of the FVU and the change in the population to which it would be used, blind adoption of the FVU was considered inappropriate.</p> <p>A protocol for validating the FVU in Sierra Leone is presented. The major methodologic problems addressed were definition of asymptomatic male urethral gonococcal carrier, the selection of the study population, and quality control in the laboratory.</p> <p>The finding of a sensitivity of 0.9 or greater for the FVU will be considered valid for the study.</p> / Master of Science (MS)

<p>The effects of liver on pituitary prolactin (PRL) secretion were investigated using an in vitro organ culture system. It was determined that various preparations of liver when coincubated with pituitary tissue resulted in a diminished PRL content in the bathing culture medium. Female Wistar rats (>200gm) provided the source for liver chunks (~150mg) that were coincubated with pituitary tissue obtained from female Wistar rats (>200gm) primed with estradiol-17-β and progesterone. The PRL content of the culture medium obtained from the liver - pituitary coincubate was reduced significantly (p<.001) compared to control. This effect could not be attributed to PRL degradation and/or binding to liver and was therefore interpreted as inhibition of secretion. The effect was partly but not completely antagonized by the addition of Haldol at concentrations ranging up to 1000nM.</p> <p>It was also noted that the diminished PRL content was observed when methanol extracts of male and female livers were coincubated with male and female (primed and unprimed) pituitary tissue. It is concluded that factors associated with liver and extracts of liver inhibit the secretion of prolactin. These factors are thought not to mediate all of their actions through the dopamine receptor as maximally effective concentrations of Haldol only partially eliminate this inhibition.</p> / Master of Science (MS)

<p>Endogenous protein kinase activity was detected on the external cell surface of both normal and Rous sarcoma virus (RSV)-transformed chick embryo fibroblasts (CEF). Cells growing in plastic dishes were incubated with [Υ-³²P]ATP for 20 minutes. Under the conditions employed, only proteins located on the external cell surface were labeled, as the radioactivity could be removed by mild trypsin treatment. In addition, exogenous histones were phosphorylated when added to the reaction mixture. The addition of cAMP and cGMP to the reaction had virtually no effect on ³²P incorporation, suggesting there is little or no cyclic nucleotide-dependent protein kinase activity present on the external cell surface. Cell surface protein kinase activity was higher in RSV-transformed CEF than in normal CEF, and, using a temperature-sensitive src mutant, this difference was found to be transformation-specific. Several differences were observed in the cell surface proteins phosphorylated in normal and transformed cells, and at least two of these were transformation-specific. These data suggest that changes in external cell surface protein phosphorylation are associated with RSV transformation and thus could play a role in the formation of the transformed cell phenotype.</p> / Master of Science (MS)

<p>This thesis intends to study the effects of introducing a pharmacy-service-package in three health districts of the State of Tlaxcala, Mexico. Each district consists of several villages with rural health centres. They have small variation in size and their total economy and natural resources are almost equal. Districts have some features in common, none of them have experienced the "intervention" and all have the same health care system.</p> <p>The investigative method followed consists of randomly allocated intervention and then surveying the districts at two points in time, noting the changes that occur in the interim. Thus it basically requires two sets of observations, one for what might be called the before period (from 1977-1981), the other for what might be called the after period (1982-1983).</p> <p>These districts have already been studied by the University of Mexico. From this survey and auxilliary resources, enough information has been assembled that will be used to determine the initial health care conditions of the districts in the base line period. The investigation of the follow-up and terminal period are the author's responsibility. This work will consist of the designing of a study to collect comparable data and the designing of the analysis to provide evidence of the most important changes that will take place during the study.</p> <p>Chapter One contains an overview of Mexico. Chapter Two describes the current health care system in Mexican rural areas with emphasis on pharmaceutical services. A review of the literature is presented in Chapter Three. In an attempt to establish some basis for the design of a study, existent data is presented in Chapter Four. In this chapter also a proposed protocol presents the design of a definitive study to analyse the effects of pharmacy services in those districts.</p> / Master of Science (MS)

<p>In our investigations concerning the control of synthesis of mouse alpha-1-protease inhibitor (α1Pi), also called alpha-1-antitrypsin (α1AT), a major inhibitor of serum proteases, we had reason to attempt to develop a monoclonal antibody to this molecule to clarify some apparent molecular heterogeneity, as conventional approaches to separate the isoproteins had met with limited success. We immunized Lewi rats with purified mouse α1Pi and fused the immune spleen cells with mouse SP2 plasmacytoma cells after optimizing some of the fusion parameters such as the source of polyethylene glycol (PEG), its concentration and exposure time to cells. In addition, we examined two different fusion protocols for their ability to produce xenogenic rat X mouse hybrid cells. Several hybridomas were produced, one in particular secreting rat IgM specific for mouse α1Pi. Screening of the positive clones was carried out by modified ELISA and radioimmunoassays. Characterization of the cell product was completed by SDS-PAGE and radioimmunoelectrophoresis. Specificity of the secreted immunoglobulin (D7-IgM) was determined using crossed radioimmunoelectrophoresis with ³⁵S-methionine labelled monoclonal antibody. The establishment of a mouse ascitic form of the hybridoma was not successful even after prolonged subcutaneous adaptation of the hybridoma line in ALS treated, bone marrow reconstituted, X-irradiated Balb/c recipients. Mice bearing the solid tumor exhibited pathology in the liver in the form of discrete necrotic lesions suggesting metastatic localization of the hybridoma in the liver and local production and interaction of the monoclonal antibody with the hepatocyte via one of its secreted molecules, alpha-1-protease inhibitor.</p> / Master of Science (MS)

<p>Each year, educational programs, with the responsibility of graduating health professionals, face the dilemma of selecting the most suitable candidates from numerous applicants. Since the number of positions in these classes is limited, the goal underlying the admission procedure is to identify those most likely to succeed.</p> <p>Nursing programs, in particular, have had difficulty in realizing this goal. Despite the use of a variety of selection devices by different schools, the attrition rate of nursing students consistently remains between 30 and 40 percent.</p> <p>The reduction of this attrition rate, by careful examination of various admission methods, will be addressed in this thesis. First, the scientific literature examining attrition and admission procedures in nursing, as well as other disciplines, will be reviewed. Following this, the extent of the attrition problem, specifically in the baccalaureate nursing program at McMaster University, will be explored by means of a retrospective analysis of four years of data. Finally, the design of two randomized controlled trials, each addressing one of two categories of applicants, will be described.</p> <p>The McMaster baccalaureate nursing program presently assesses candidates applying for a position directly upon completion of secondary school on the basis of Grade 13 marks. A second group, 'special' applicants, are considered on the basis of interview scores. The designs will examine two selection devices--the autobiographical letter and the team interview.</p> <p>An additional feature of the proposed study is that all applicants will participate in each admission procedure, but will be blind to the device used to determine their admission. Data about the alternate selection tools will be available for analysis at the end of the study.</p> <p>The validity of the selection devices will be assessed by the examination of four outcome measures. First, success of students in terms of remaining in the program, failing, and withdrawing will be monitored. Second and third, grades in nursing courses for the first two years of the program will be recorded, as well as grades in nursing science courses. Lastly, first and second year tutors will be asked to evaluate the students in terms of their abilities in self-directed learning, problem-solving, interpersonal relations, and self-evaluation.</p> / Master of Science (MS)

<p>Up until the last decade, physicians were content to base management decisions in postoperative surgical patients on the clinical diagnosis of deep vein thrombosis (DVT). Subsequently, multiple studies have demonstrated the insensitivity of clinical diagnosis. Pulmonary embolism (PE) is the most common preventable cause of in-hospital death, which no doubt reflects the insensitivity of clinical diagnosis. Multiple randomized trials indicate that low-dose subcutaneous (sc) heparin and intravenous (IV) dextran are effective for preventing death due to pulmonary embolism in postoperative general surgical patients. Other approaches effective against venous thromboembolism are: intermittent pneumatic leg compression (IPLC) and screening with ¹²⁵I-fibrinogen leg scanning. We have performed a cost-effective analysis in 1,000 patients over the age of forty years undergoing major elective surgery comparing the prophylactic approaches described above with the "no-programme" situation (early ambulation but no other active prophylaxis). The total cost (Canadian dollars) and total effects (deaths from pulmonary embolism averted) are as follows: s.c. heparin $35,714 for 7 lives saved; IPLC $55,803 for 7 lives saved; IV dextran $137,235 for 6 lives saved; leg scanning $396,599 for 7 lives saved; and the "no-programme" situation $53,472 for 8 lives lost. The "no-programme" situation is clearly cost-ineffective. Incremental cost-effectiveness analysis indicates that s.c. heparin is the most cost-effective, followed by IPLC. Dextran and leg scanning, although effective, are both expensive; therefore s.c. heparin or IPLC prophylaxis are preferred.</p> / Master of Science (MS)

<p>The Ames Assay is a battery of tests which measures the mutagenicity of chemical substances. In order for its results to be relevant to human health, Ames Assay mutagenicity must relate to human cancer in a biologically credible and comprehensive way. It must also correlate with other measures and attributes of carcinogenicity. The evidence presented demonstrates its biologic credibility, but illustrates the improbability of its being a comprehensive measure of all attributes of carcinogenesis. Agreement between the Ames Assay and animal cancer studies, other short-term bioassays, human carcinogens, and chemical structures predictive of carcinogens is presented. The range of possible predictive accuracy for the Ames Assay is calculated from these agreement evaluations. A hypothetical model is developed to test whether the Ames Assay is a sufficiently valid predictor of human carcinogenesis regardless of the extremes of this range. It is not sufficiently valid in the lower half of the range. So more work must be done to define precisely its accuracy.</p> <p>The problems of applying the range of accuracy of a laboratory test of pure substances to biologic and environmental samples are explored. Unsolved problems in collection and analysis of airborne samples are identified. A study design is presented which minimizes the chance of bias in collecting airborne samples. The limitations of the laboratory procedure and the problems of sample collection are brought together in two continuous flow schemes. Together these demonstrate the unsolved biologic and biostatistical problems in validating the Ames Assay.</p> / Master of Science (MS)

<p>A retrospective cohort analytic study will be conducted to compare the incidence of abnormal reproductive outcomes of members of the Canadian Society of Laboratory Technologists with that of members of the Canadian Physiotherapy Association in order to identify exposures which may pose a threat to the reproductive process.</p> <p>Members of each of the organizations will be mailed a questionnaire requesting demographic and health information. A second questionnaire requesting detailed information about reproductive outcomes will be sent to those subjects who have experienced pregnancies in the previous five years. Additional mailings by conventional mail and special delivery wil be used to increase the response rate. Subjects who have given birth to stillborn children or children with congenital abnormalities and a random sample of those who have had miscarriages will be asked to provide written consent for their physician to be contacted to provide confirmatory information from their medical record.</p> <p>The analyses will compare rates of abnormal reproductive outcomes in total and by specific type between laboratory technologists and physiotherapists controlling for age, parity, smoking status, infection, X-ray, drug and alcohol exposure during pregnancy.</p> / Master of Science (MS)

<p>Hereditary muscular dystrophy of the chicken is a primary defect of muscle which is expressed specifically in the fast twitch, focally innervated glycolytic muscle, while slow tonic, multiply innervated oxidative muscles are spared disease characteristics (for review, Cosmos et. al., 1979b). Since motor nerves influence the characteristics of skeletal muscles, and since slow tonic muscles in the chicken do not express dystrophic phenotypes, it was decided to replace the motor innervation of the fast twitch posterior latissimus dorsi (PLD) muscle with the motor innervation of the slow tonic anterior latissimus dorse (ALD) muscle within a dystrophic chicken, in order to alter the fate of the dystrophic fast twitch muscle. Selected mechanical, histochemical and structural properties of the ALD and PLD muscles of normal (White Leghorn) and dystrophic (Storrs line) chickens 15-800 days ex ovo were compared to determine which of these properties were altered as a result of the disease, and to provide baseline data for the analysis of the cross reinnervation experiments. ALD muscles of dystrophic chickens exhibited normal phenotypes, i.e. slow tonic isometric contraction in response to nerve stimulation in vivo, acid and alkaline stable myosin ATPase activity, "en grappe" innervation, weak phosphorylase (Pase), strong succinic dehydrogenase (SDH) enzymic activities and peripheral location of nuclei. PLD muscles of dystrophic genotype demonstrated structural and histochemical alterations but retained contraction and relaxation times characteristic of fast twitch muscle of normal genotype. Further, they exhibited focal "en plaque" innervation and alkaline stable myosin ATPase activity similar to that of normal PLD muscles. The abnormalities identified in the dystrophic PLD included the following: lower muscle weight, abnormal size and shape of fibres, increased number of internal nuclei, abnormal Pase and SDH enzymic activities and lower twitch and tetanic tensions. The surgical cross reinnervation between the ALD nerve and the PLD muscle was performed at hatching. The muscles were examined at various time intervals postoperatively using the criteria established in the study of the unoperated muscles. Self reinnervation of PLD muscles by their own nerves, and cross reinnervation with normal chickens served as control experiments. Fibres of both normal and dystrophic PLD muscles which had been successfully cross reinnervated acquired mechanical, structural and histochemical properties characteristic of the ALD muscle. Thus, muscles of both genotype responded similarly to the ALD nerve. These results established that the PLD muscle of dystrophic chicken is able to accept the new innervation, and is as capable of responding to the influence of the ALD nerve as is the normal PLD. Furthermore, the successfully cross reinnervated fibres are spared disease characteristics. The present cross reinnervation experiment demonstrates, for the first time, an experimental manipulation which interferes with the expression of phenotypic characteristics of dystrophy during development ex ovo. The results support the rationale underlying the present study: the PLD muscle of dystrophic genotype is unable to respond appropriately to the demand from its own motor nerve to complete successfully the transition from embryo to adult metabolism, thus expressing the dystrophic phenotypes. However, when this request is removed by cross reinnervating the PLD muscle with the ALD nerve, the dystrophic phenotype is not expressed. These findings strongly suggest that regardless of the time during development when slow tonic characteristics are achieved, i.e. either during development in ovo or by surgical manipulation ex ovo, slow tonic fibres are spared dystrophic phenotypes.</p> / Doctor of Philosophy (PhD)