In order to examine the effects of prelatent/latent iron deficiency on physical work capacity and selected muscle enzyme activities, forty female subjects were studied before and after eight weeks of supplementation with either oral iron or a matching placebo. Initially, female volunteers engaged in regular endurance running were screened for iron deficiency by blood analysis (serum ferritin and hemoglobin). Forty non-anemic subjects with deficient iron stores underwent physiological and anthropometric tests to obtain a comprehensive profile. The specific physical work capacity tests were alactic and lactacid power on the Wingate cycle ergometer test, lactacid capacity on the anaerobic speed test, anaerobic (ventilatory) threshold using gas exchange variables, V0₂ max. and the max. treadmill velocity during the V0₂ max. test. Muscle biopsy samples pre-, and post- treatment were assayed for citrate synthase and alpha-glycerophosphate dehydrogenase activity. Treatment was oral iron supplementation (320 mg ferrous sulfate = 100 mg elemental iron taken as SLOW-Fe® twice a day) or a matching placebo. The subjects were randomly assigned to one of the treatment groups and a double-blind method of administration of the supplements was used. It was hypothesized that work capacity would be enhanced following oral iron supplementation, possibly due to the repletion of iron containing oxidative enzymes important in energy production. Results could not strongly support this hypothesis with the difference between the two groups on the work capacity and enzyme activity variables being statistically nonsignificant. Serum ferritin values rose from a mean of 12.4+4.5 to 37.7+19.7 ngml⁻¹ for the experimental group and 12.2±4.3 to 17.2±8.9 for the controls; (p=0.0025). Hemoglobin levels remained fairly constant for both treatment groups; 13.4±0.6 to 13.5±0.5 gdl⁻¹ (experimental), and 13.0±0.6 to 13.1+0.5 (control); (p=0.6). Pre to post values on the work capacity variables, experimental vs control respectively were: Alactic power, 8.8 to 8.4 watts-kg⁻¹ body wt. vs 8.4 to 8.2; lactacid capacity, 6.9 to 6.9 watts-kg⁻¹ body wt. vs 7.0 to 6.0; anaerobic speed test, 41.3 to 45.1 seconds vs 43.7 to 44.8; anaerobic threshold, 7.4 to 7.5 mileshour⁻¹ vs 7.2 to 7.2; V0₂ max, 51.3 to 52.7 ml-kg⁻¹ min⁻¹ vs 50.6 to 50.6; max velocity during V0₂ max, 9.8 to 9.8 mileshour⁻¹ vs 9.6 to 9.5. Except for alactic power, the change in work capacity favored the iron treated group. Noting this trend, further study may be warranted. Prelatent/latent iron deficiency appeared not to depress the activities of the two enzymes measured. Cytoplasmic alpha-glycerophosphate dehydrogenase activity rose from 0.066 to 0.085 units for the experimental group (p=.58) vs .058 to .066 for the control group and citrate synthase activity changed from 0.047 to 0.048 (experimental) vs 0.039 to 0.042 (control). It can be concluded that eight weeks of iron supplementation to prelatent/latent iron deficient, physically active females does not significantly enhance work capacity nor the activity of 2 oxidative muscle enzymes (citrate synthase and cytoplasmic alpha-glycerophosphate dehydrogenase). Within the limitations of this study the presence of a serum ferritin below 20 ng-ml⁻¹ does not pose a significant handicap to anaerobic or aerobic capacity. / Graduate and Postdoctoral Studies / Graduate

The purpose of this study was to compare the relationship between immersion running and treadmill running through the measurement of cardiorespiratory parameters. Sixteen subjects completed two exercise protocols to exhaustion. The treadmill running protocol was initiated at 3.08 m*s-l and increased a 0.22 m*s-l every sixty seconds. The immersion running protocol utilized an immersion running Ergometer (IRE). The IRE is similar to a tethered swim machine. The initial weight was set at 1 kg and Increased a 1/2 kg every sixty seconds. Heart rate (HR), oxygen consumption (V02), ventilatory equivalent (VE/V02), and minute ventilation (VE) were determined at ventilatory threshold and at maximal effort, HR, V02, VE/V02 and VE were analyzed by MANOVA (RM). Tidal volume and frequency of breathing were collected for four subjects at ventilatory threshold and at maximal effort (no statistical analysis). Two subjects who had completed the initial exercise protocols volunteered for a follow up study of blood flow distribution testing (no statistical analysis). These subjects were injected with Tc-99 2-methyloxy isobutyl isonitrlle at ventilatory threshold during immersion and treadmill running. Imaging was performed with a Selmans Gamma Camera at the UBC Dept. of Nuclear Medicine. V02 and HR at ventilatory threshold and maximal effort were significantly lower (P < .05) during immersion running. VE/V02 was significantly greater at maximal effort during immersion. Minute ventilation was unaffected by immersion, however, there was a trend towards a smaller tidal volume and greater frequency of breathing. The blood flow distribution data varied considerably partially between subjects. The significant drop in V02 at maximum effort and at ventilation threshold during immersion running may be accounted for by changes in muscle mass recruitment, muscle fibre type recruitment, recruitment pattern and state of peripheral adaptation (muscular). A lower heart rate during immersion may be due to increases in intrathoracic blood volume. The trend towards a higher breathing frequency and lower tidal volume during immersion running may be due to the increased effort to breath caused by hydrostatic chest compression. The significant increase in VE/V02 at maximal effort during immersion running was due to the significant drop in V02. It may be concluded that immersion running causes significant changes in cardiorespiratory parameters at ventilatory threshold and at maximal effort. Research is needed to investigate the significance of the changes. / Education, Faculty of / Curriculum and Pedagogy (EDCP), Department of / Graduate

My thesis is divided into 4 major sections. The first section is devoted in part to a description of the biochemical abnormalities in the metabolism of homocarnosine (y-aminobutyryl-L-histidine, HCarn) occurring in a patient with homocarnosinosis. The patient studied and two of her siblings have a progressive neurological disorder with grossly elevated concentrations of HCarn in their CSF. HCarn content was four times higher in a biopsy from the patient's frontal cortex than in biopsied cortex from a large group of control subjects. Using new techniques for the measurement of the HCarn synthesizing and catabolizing enzymes, it was found that the activity of HCarn-Carn synthetase was not increased in the patient's biopsy whereas homocarnosinase activity was undetectable. It is concluded that the elevated HCarn in brain and CSF in the homocarnosinosis patient is due to a deficiency of brain homocarnosinase activity. The first description of the regional distribution of the two HCarn metabolizing enzymes in human brain was also obtained. The remainder of the first section deals with a description of the neuropharmacological properties of HCarn. Intraventricular injection of HCarn in the rat produced hyperexcitability and in high doses, convulsions, whereas unilateral intra-striatal injection of HCarn resulted in contralateral myoclonus. The results of these experiments are consistent with the possibility that HCarn may be involved in the neuronal excitability of brain. The second section describes experiments which test the hypothesis that the content of the inhibitory neurotransmitter GABA is altered in the autopsied brains of some patients dying with schizophrenia. The mean content of GABA was reduced by 20-25% in nucleus accumbens, caudate nucleus, frontal cortex and thalamus of the schizophrenic patients as compared to a control group. However, the differences were found to be statistically significant for only the caudate and thalamus. Extraneous factors such as age of patient at death and prolonged drug treatment did not readily explain the observed reduction in GABA content. The results of the investigation suggest an association between a deficiency of GABAergic function in certain brain areas with some forms of schizophrenia. The third section describes experiments which test the hypothesis that a deficiency of aspartate found in the cerebellar cortex of some patients with dominantly inherited cerebellar disorders might be due to reduced activity of two enzymes involved in the synthesis of aspartate, namely, aspartate aminotransferase and pyruvate carboxylase. No deficiency of either enzyme was observed in the cerebellar specimens studied. The results of this investigation suggest that the aspartate deficiency in cerebellar cortex found in some dominantly inherited cerebellar disorders does not result from a deficiency of either of these two brain enzymes. In the final section, experiments are described which study the effects of chronic administration of Y-vinyl GABA and of hydrazine on the contents of GABA and other amino compounds in rat brain. Both of these compounds are presently under consideration for use in clinical trials on patients with disorders involving a brain GABA deficiency. Chronic administration of either y-vinyl GABA or of hydrazine markedly increased brain GABA content in the rat. Prolonged treatment with y-vinyl GABA, but not hydrazine, produced a decrease in the activity of glutamic acid decarboxylase (GAD) in rat brain. Since GAD is localized to a large extent in nerve endings, the possibility exists that y-vinyl GABA might reduce the amount of GABA available for release at synapses, a potentially undesirable effect. The contents of many brain amino compounds other than GABA were markedly altered by both drugs. Since the potential harmful effects of these unexpected biochemical alterations in brain are unknown, the nonspecific effects of Y-vinyl GABA and hydrazine are disturbing. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

M.Cur. / Midwives are responsible to assess pain before treating it; then they should reassess the pain to evaluate the effectiveness of the interventions and plan future therapy. Accurate and objective measures of labour pain continue to be scarce and the discrepancy in labour pain perceptions between parturients and health-care providers remains challenging. Various pain measurement tools are currently in use measuring chronic and acute pain, but many problems were encountered applying these methods to the woman in labour. The charts were detailed and required too much time to complete. The aim of the study was to develop a multidimensional labour pain assessment instrument to assist clinicians and midwives with labour pain control. Objectives for developing a valid and reliable instrument to accurately measure labour pain included refinement of the labour pain assessment instrument developed from literature, testing of the refined instrument on patients during labour, compilation of a final instrument and development of guidelines on how to implement the labour pain assessment instrument in nursing practice. A descriptive and exploratory approach was used to describe, evaluate, observe, explore and assemble new knowledge on assessment and measurement of pain during the first stage of labour. Development of the instrument was addressed in the literature chapter. The research was conducted in three phases, combining qualitative and quantitative research. During phase one, the instrument was refined in two stages. Focus group interviews were conducted with members regarded as knowledgeable in the field of normal labour who evaluated the face and content validity of the instrument. The most senior people teaching Midwifery at all South African universities evaluated the face and content validity of the instrument with an open-ended questionnaire thereafter, using the Delphi technique. The analysis of the first Delphi round was compared to the focus group analysis. The instrument was altered and submitted to the Delphi experts in a second open-ended questionnaire to confirm the alterations. During phase two, the altered instrument was tested in private and provincial hospitals. Testing of the altered labour pain assessment instrument on patients in active labour yielded quantitative data. A statistician at the University of Johannesburg was consulted to assist with tabulation, frequencies and statistical tests needed. The midwives from the private and provincial hospitals also completed the second Delphi open-ended questionnaire. A Likert scale was included in the second Delphi instrument as midwives have less time available to complete questionnaires. The qualitative analysis of their responses was compared to those of the second Delphi round experts to avoid an inflated estimate of validity that might have been brought forth by the very small second Delphi round sample. The instrument was finally altered and, during phase three, guidelines were developed on how to implement the labour pain assessment instrument in nursing practice.The experts concluded the instrument as a simple tool that can measure and assist with labour pain control, assess the progress of labour and the patient’s condition, assist with training, guide inexperienced midwives in pain assessment and serve as a research tool. The labour pain assessment instrument can be a valuable tool in assisting clinicians and midwives with labour pain control during the first stage of labour and initiate standards for pain measurement. The challenge remains to convince institutions to improve pain control during labour and protect themselves from potential pain maltreatment litigation by using a valid and reliable pain measurement instrument.

In order to assess flexibility in acquiring and using conflicting response rules, rats with selective lesions of the NBM or sham-lesion controls were subjected to serial reversal training in a simple operant discrimination paradigm. The NBM lesion group did not differ from the control group in acquisition of the original rules; the NBM lesion group required more time to master the changes in rules in the first reversal, but not in subsequent reversals.

The main problem of this study was to determine if a significant strength difference existed between the mirror muscles of six muscle groups in the dominant and nondominant legs of University of the Pacific male soccer players at differing contraction speeds as measured by the Cybex II Isokinetic Dynometer.

The purpose of this study was to investigate the effects of fatigue on the accuracy and selected biomechanic variables of jump shot performance. Five subjects were filmed with two high speed cine cameras during pre-fatigue and post-fatigue conditions. The accuracy data were acquired by recording the results of thirty pre-fatigue and thirty post-fatigue, fifteen foot jump shots. The biomechanical data were gathered from film records of every third trial in the pre-fatigue and post-fatigue shooting. Biomechanical analysis variables were acquired using a ten point body model. With these data the following biomechanical variables were analyzed in the pre-fatigue and post-fatigue condition: (1) height of release (2) angle of release (3) absolute shoulder flexion angle at release, and (4) angle of shoulder abduction. Results of the study showed that there is no decrease in accuracy of jump shot performance after fatigue. Fatigue slightly effects the height of release in jump shot performance. Fatigue does not decrease the angle of release in jump shot performance. Fatigue does cause a decrease in the shoulder angle in jump shot performance. There is no decrease in shoulder abduction after fatigue . The study also showed that there are apparently many biomechanical techniques in high percentage shooters, and the presence of fatigue affects selected jump shot biomechanics differently in each shooter.

Circadian systems drive daily oscillations in physiology in organisms from bacteria to humans. These oscillations are coordinated by specific changes in environmental cues, the most important of which is light. In animals, circadian regulation of brain function creates rhythmic patterns in behaviors like sleep. Circadian dysregulation is a common feature of many human diseases and environmental causes of circadian disruption increase susceptibility to many diseases including cancer. Importantly, circadian disruption is also commonly seen in hospitalized patients, which could have negative effects on health outcomes. Understanding the basic biology of circadian-regulatory systems and their physiological functions is essential for identifying the impact of circadian rhythms on human health. This dissertation describes a body of work using the fruit fly Drosophila melanogaster to better understand circadian regulation and its impact on behavior and physiology.

The purpose of this study is to assemble information needed to assess, understand and hopefully correct muscular hyperfunction that is related to tongue tension in singing and speech which inhibit freely, efficiently, and comfortably produced beautiful singing. This text will include a definition of freely produced, fully resonating tone for beautiful singing, major components of vocal technique, physiology related to singing and speech production, hyperfunctions associated with tongue tension, tongue involvement in the articulation of the four major singing languages, and will present exercises for training the muscles of coordination in a manner conducive to singing and speech.

The cerebellum is well-known for its ability to integrate diverse internal and external stimuli, forming associations which serve as a basis for the construction of predictive models. Though traditionally studied in the context of motor learning, mounting evidence indicates that cerebellar learning may play an analogous role in many non-motor functions, including autonomic regulation and reward processing. Using combinatorial approaches of neuroanatomical tracing, electrophysiology, and behavioral studies, we investigated whether cerebellar learning extends to the domains of feeding behavior and gastrointestinal regulation, wherein prediction is critical for optimally timing food seeking and digestion in order to maximize nutrient acquisition while minimizing risk and energetic cost. Our results show direct anatomical connections between the cerebellum and known feeding centers, including the lateral hypothalamus, nucleus of the solitary tract, and parvocellular reticular nucleus. In addition, a localized area of the rostral cerebellum was found to respond to gastric distension and drive gastric emptying. Finally, we show that cerebellar activation drives robust, short-latency ingestive responses in awake, sated mice. Collectively, our results implicate the specific, interconnected cerebellar regions of Lobules II & III and the rostral fastigial nucleus, which we believe may represent one or more microzones devoted to integrating pre-and post-ingestive signals for control of feeding and digestion.