Thesis (doctoral)--University of Tampere, 1984. / Includes previously published articles. Includes bibliographical references (p. 42-51 (1st group)).

Cholecystokinin (CCK)-like immunoreactive materials have been localized in neurons with cell bodies in the colon and axons in the IMG of the guinea pig. The physiological significance of neuronal CCK in sympathetic prevertebral ganglia is unknown. The goal of the present studies is to test the hypothesis the CCK is a neurotransmitter in the IMG of guinea pig and rabbit. In vitro IMG preparations with or without a segment of the colon attached were utilized to conduct intracellular recordings of potentials elicited in the neurons by pressure-ejected CCK₈. The peptide triggered a depolarization with rapid onset (1-5 s) and a rate of rise (1.6 ± 0.4 mV/s) in 95% of the neurons tested. Values of the ED₅₀ for effecting depolarization average 1.1 ± 0.5 pmoles. In 59% of the cells, the depolarization was associated with a decrease in R(in) and in 20% with an increase. The remaining cells showed no change in R(in). G(Na) and G(K) were increased and decreased, respectively; potential-dependence characteristics revealed a null potential of 36 ± 9 mV in those cells exhibiting a decrease in R(in). Gastrin, caerulein, and CCK₂₇₋₃₃ effected similar depolarization. CCK₈-evoked depolarization imitated the depolarization produced either by colon distension or by nerve stimulation. Upon repeated administration of CCK₈, the response of the cells to the peptide underwent tachyphylaxis. In addition, CCK₈ desensitized the depolarization evoked by stimulation in 50% of the cells. Furthermore, in an equal percentage of neurons, CCK₈ depressed responses of the colon distension-induced depolarization. The CCK₈ has both pre- and postsynaptic sites of action is supported by lowering Ca²⁺ and administering TTX (3 μM), which caused no effect and depressed 30% of CCK-induced depolarization respectively. Spantide (SP antagonist) blocked the response to SP, but not to CCK₈, in 5 out of 6 neurons, indicating separate receptor sites for SP and CCK₈. Moveover, completely desensitizing the cell response to SP or VIP did not cross desensitize its response to CCK₈ as observed in 6 neurons. In the rabbit IMG, the physiological significance of CCK₈ excitation is unknown, since colon distension did not elicit any depolarization. These results support the hypothesis that CCK₈ or a related peptide is a neurotransmitter mediating reflex activity between the colon and the IMG in guinea pig.

Cette thèse se situe dans le domaine de l’informatique orientée service. Elle propose un ESB (Enterprise Service Bus) autonomique, c’est-à-dire capable de s’autogérer sur un ensemble d’aspects. Cet ESB, nommé Cilia autonomique, permet de construire des applications de médiation sensibles au contexte.Précisément, la version autonomique de Cilia, que nous proposons, permet l’optimisation de l’utilisation des ressources de la plate-forme d’exécution et l’adaptation dynamique des chaînes de médiation au niveau de la configuration et de la topologie. Notre framework permet également de présenter à tout moment un modèle simplifié des phénomènes liés à l’exécution des chaînes et, ainsi, de faciliter le raisonnement et la prise de décisions d'adaptation.Les travaux de cette thèse ont été validés dans le cadre de l’informatique pervasive. En particulier, Cilia autonomique a été utilisé et instrumenté pour la mise en oeuvre d’applications de maintien à domicile et de suivi de la santé des usagers. Les résultats sont disponibles en open source. / This PhD work takes place within a broader context of service-oriented computing. Precisely, it defines an autonomic Enterprise Service Bus (ESB) with self-management ability regarding certain aspects. This ESB, named autonomic Cilia, allows the simplified development of context-aware mediation applications. Autonomic Cilia permits the runtime optimization of resources used by its execution machine and the dynamic adaptation of mediation chains, regarding configuration and topology. Our framework can also retrieve at any time a simplified model of the mediation chains execution. Such models enable reasoning and decision making easier to implement for mediation developers. The work presented in this thesis has been validated in the context of pervasive computing. In particular, autonomic Cilia has been used and instrumented to implement healthcare applications in smart homes. The autonomic Cilia framework is available in open source.

Background & Rationale: Heart rate variability analysis has provided scholars and clinicians with a powerful non-invasive tool for the assessment of cardiac autonomic function in health and disease. However, the interpretation of the information provided by this technique would be greatly facilitated by a more precise definition of 'normality'. The purpose of this investigation was to examine the alterations in cardiac autonomic function across a broad spectrum of ages in healthy males and females. Methods: Heart rate variability data during 20 min supine rest and orthostatic stress (10 min free standing) as well as 24-hour ambulatory Holter ECG recordings were obtained on 123 healthy volunteers (72 female/51 male). Subjects were arbitrarily classified into five categories: pediatric (PED; 5-12 yrs, n=22, 12 female:10 male), adolescent (ADO; 13-17 yrs, n=21, 13 female:8 male), adult (ADU; 18-30 yrs, n=26, 13 female:13 male), middle aged (MDA; 31-60 yrs, n=24, 15 female:9 male) and elderly (ELD; 61+ yrs, n=30, 19 female:11 male) age groups. Power spectral analysis (autoregressive) was determined from supine and standing acute data sets as well as six evenly spaced one hour periods during the Holter recording. Time domain variables (pNN50, R-MSSD, SDNN, SDANN & SDNN index) were derived from the 24-hour data sets. Results: Heart rate in the supine position declined progressively from age 5 years to 30 years but showed no further changes thereafter. In contrast, power spectral measures remained relatively stable in the younger age groups but subsequently exhibited a significant shift toward a higher LF:HF area signifying sympathetic dominance (or vagal withdrawal) in the MDA and ELD subjects. The heart rate and spectral response to orthostasis was most dramatic in the ADO subjects and exhibited a progressive decline in the three older age groups. With respect to the time domain variables, those parameters characterizing short term variability (pNN5O & R-MSSD) were stable in the PED, ADO and ADU subjects but significantly diminished in the two older age groups. In contrast, time domain variables encompassing long term (SDNN & SDANN) and intermediate (SDNN index) oscillations exhibited age-related increases reaching peak values in the ADU subjects and declining progressively thereafter. Power spectral analysis of the six evenly spaced one hour periods of the 24-hour holter recording revealed a diminished circadian rhythm for the majority of the frequency domain indices in the two oldest age groups. Conclusions: The present investigation revealed substantial evidence supporting the existence of an age dependent change in cardiac autonomic function. However, this process appeared to act homogeneously across gender. The similarity of these age dependent changes to those previously observed in pathological conditions commonly associated with autonomic neuropathy serves to emphasize the importance of HRV research aimed at the establishment of reference standards in healthy populations and a more precise definition of 'normal' autonomic neurocardiac function. / Thesis / Master of Science (MSc)

Spontaneously hypertensive rats (SHR) are a well accepted model of primary hypertension. Among other features common to human hypertension, these rats exhibit sympathetic hyperactivity. The neurons of the superior mesenteric ganglion (SMG) from SHR display enhanced collateral sprouting, higher firing rates and hyperinnervation of the mesenteric arteries compared to the SMG neurons from age-matched, normotensive Wistar-Kyoto (WKY) rats. Furthermore, SMG neurons in SHR are exposed to different conditions than are SMG neurons from WKY rats, including enhanced oxidative stress, increased afferent stimulation, and an altered hormonal environment. In order to identify proteins with potential involvement in the establishment or maintenance of peripheral sympathetic hyperactivity in SHR, we used proteomic techniques to search for differences in protein expression between the SMG of SHR and the SMG of WKY rats at 16 and 22 weeks of age. We found an upregulation of predominantly fetally expressed T1 domain and haptoglobin and a downregulation of serine protease inhibitor 2.1 in SHR relative to WKY rats at 16 and 22 weeks; Apolipoprotein-A1 was also found to be upregulated in 22 week SHR SMGs compared to age-matched WKY SMGs. These identifications improve our understanding of the ganglionic microenvironment in SHR and represent targets for the development of novel therapies to treat primary hypertension. Hypertension is one of the defining components of the metabolic syndrome, together with insulin resistance, visceral adiposity and hyperlipidemia. Non-alcoholic fatty liver disease (NAFLD) is also a common feature of the metabolic disorder, and thus primary hypertension and NAFLD are common comorbidities. Despite these clinical connections, very little is known about the effects of primary hypertension on hepatic physiology. We used proteomic techniques to search for evidence of significant involvement of the liver in SHR phenotype at the molecular level. We detected changes in the expression of several proteins involved in the regulation of oxidative stress and lipid metabolism which together show that the liver is strongly involved in the pathologies associated with hypertension. Our results suggest several novel mechanisms for the initiation of oxidative stress in SHR which could contribute to new advances in the treatment of metabolic abnormalities associated with hypertension. / Thesis (Master, Anatomy & Cell Biology) -- Queen's University, 2009-10-27 10:11:05.052

The hypothesis that high heart rate and low perceived skill would be associated with greater return of fear than low heart rate and high perceived skill was investigated in a group of anxious musical performers (N=63) in response to an anxiety-reduction training program. Musicians were taught progressive muscle relaxation and attention-focusing skills over the course of four weekly meetings. Return of subjective fear was assessed between training program sessions and at a three-month followup assessment. The three major fear response systems were measured at pre, post and followup assessments and throughout the three training program sessions that included behavioural rehearsal. Subjects (pianists, violinists and vocalists) performed a short piece before an audience (at assessments) or before their fellow group members. Performance quality ratings by independent musicians served as the behavioural measure, anticipatory heart rate as the physiological measure, and subjective units of distress scales as the subjective measure. In addition, subjects completed memory questionnaires, designed to assess their recall of the setting and their response to previous performances, and thought questionnaires, to provide data pertinent to processes hypothesised to underlie return of fear. Four classification groups (high heart rate, low perceived skill; high heart rate, high perceived skill; low heart rate, low perceived skill; and low heart rate, high perceived skill) were formed on the basis of median splits of heart rate and perceived skill pre-assessment levels. At post-assessment, each group demonstrated fear reduction, heart rate reduced in high-heart-rate subjects, and performance quality improved overall. Followup return of fear was evident in high-heart-rate subjects regardless of initial perceived skill status, and was not dependent on initial fear levels. Perceived skill was not associated with return of fear. High-heart-rate subjects also overestimated their level of fear for previous performances, and reported more anxious thoughts and thought resensitization between performances. High non-performance heart rate was associated with greater return of fear only in extreme group analyses. Post-hoc analyses compared subjects who did (n=24) and did not (n=25) display followup return of fear. Return-of-fear subjects, in general, had higher heart rates and lower perceived skill than no-return-of-fear subjects, and tended to report thought resensitization between post and followup assessment. In addition, return-of-fear subjects were generally less skilled and performed on fewer occasions over the followup interval. The assessment of between-session return of fear was limited by design faults. The results were consistent with a dishabituation model of return of fear. They also lent support to Wagner's consolidation model in which an alteration of stimulus representations between exposures is believed to producedishabituation. The findings did not support the hypothesis that lack of consolidation may also arise from failure to attend to contextual cues, and hence, impaired retrieval of stimulus representations. Similarities of the data to Bower's description of mood-dependent cognitions were noted. It was suggested that salient internal autonomic cues during mood-congruent states facilitated overestimation of previous fear, expectation of distress and return of fear. Finally, research possibilities and treatment implications were considered. / Arts, Faculty of / Psychology, Department of / Graduate

<p>  </p> <p>Persons with a spinal cord injury (SCI) above the sixth thoracic vertebrae commonly experience autonomic dysreflexia (AD), 90 percent of individuals with this level of injury are susceptible to AD which is associated with an increase in sympathetic nerve activity. Left untreated AD causes a paroxysmal rise in blood pressure that may result in seizures, heart attack, or even death. This project investigates how AD affects QT interval, RR interval, P wave height, heart rate, and QRS width both during an event and long term to help identify potential cardiac risks for individuals with SCI who experience chronic AD. Sympathetic tone has been shown to influence QT interval changes that can be indicative of an increased risk of arrhythmia, which can be exacerbated by recurring episodes of AD.</p> <p>A rat spinal cord injury model at the T3 level undergoing colorectal distention (CRD) was used to induce AD. Electrophysiological recordings from an implanted ECG sensor and noninvasive skin nerve activity (SKNA) sensor array during normal baseline and three trials of CRD were collected on days 5, 7, 9, 11, 14, 16, 19, and 21 post-SCI. Custom MATLAB algorithms were used to identify the QRS complex and T-peaks from the implant ECG signal. QT interval measurements were taken for 2 minutes of baseline and for 2 minutes after the initiation of each CRD trial. Corrected QT interval (QTc) was calculated using normalized Bazett’s formula to account for the impact of heart rate on QT interval. </p> <p>It was found that the rats’ susceptibility and reaction to AD events varied between subacute (5-14 days) and chronic phases of SCI. During the chronic phase the incidence of AD events increased during regular occurrences of CRD as indicated by above-threshold (≥15 mmHg) blood pressure spikes. AD events also resulted in increased QT interval short term variability marking an increased risk of arrythmias. Baseline P-wave height and QTc interval were also increased while QRS complex width decreased resulting in potentially detrimental cardiac effects. This rat model showed that humans who experience recurrent AD during the chronic phase of SCI may be at increased risk for arrythmia. </p>

Some diabetic patients - particularly those with nausea and vomiting - frequently have evidence of delayed gastric emptying while other diabetic patients may in fact exhibit accelerated gastric emptying. Whether the presence or absence of symptoms of upper gastrointestinal dysfunction correlated with objective measures of gastric emptying in insulin dependent diabetic subjects was investigated. Twenty one insulin dependent diabetic patients underwent a solid phase gastric emptying scintiscan using in vivo labelled chicken patients had symptoms Thirteen patients had symptoms suggestive of gastrointestinal dysfunction (nausea, vomiting, early satiety, or constipation), while eight patients had no gastrointestinal symptoms. Eleven patients had orthostatic hypotension. All patients had been diabetic since childhood or adolescence. As a group, the diabetic patients showed a half time (T50) of gastric emptying (mean (SD) 150.0 min (163.7) that was not significantly different from that of 12 healthy control subjects (148.1 min (62.4)). Those diabetic patients without gastrointestinal symptoms and without orthostatic hypotension, however, showed a gastric emptying half time (70.1 min (41.6)) that was significantly faster than that of the control subjects. Conversely, those diabetic patients with nausea, vomiting, and early satiety (or early satiety alone) showed T50 values that were significantly greater than those of the diabetic patients without these symptoms. No correlation was found between the T50 value and the duration of diabetes, the fasting blood glucose at the time of study, or the respiratory variation in heart rate (E:I ratio). These observations indicate that highly variable rates of gastric emptying occur in insulin dependent diabetic patients, and that accelerated gastric emptying may occur in diabetic patients who have no symptoms of gastrointestinal dysfunction.

No description available.

<p>  </p> <p>Persons with a spinal cord injury (SCI) often suffer from secondary complications including the dysfunction of the autonomic nervous system below the level of injury. For persons with a SCI at or above T6, autonomic dysreflexia (AD) may be triggered by noxious stimulation below the level of injury causing rapid sympathetic hyperactivation, leading to paroxysmal hypertension. If AD is not recognized and managed promptly, this increase in blood pressure can lead to stroke, organ damage, and/or death. Currently, AD is only detected in clinical settings through continuous blood pressure monitoring. Recent studies have revealed that rapid detection of AD is possible by using extracted features from electrocardiogram (ECG) data collected non-invasively and applying a five-layer neural network.</p> <p>This project focuses on further characterization of physiological responses before and during AD to detect the overreaction of sympathetic nerve activity prior to the detrimental increase in hypertension. Using a rat model with implanted telemetry and noninvasive sensors, an acclimation protocol was developed to minimize noise and motion artifacts during data collection. We induced AD in a controlled manner using colorectal distention (CRD). We analyzed skin nerve activity (SKNA) and heart rate variability parameters in the time and frequency domain to improve the non-invasive detection of AD. A four-week acclimation protocol exposed a minimal increase in sympathetic activity during experimentation despite long periods of restraint. Results indicated an increase in SKNA features occurred about 18 seconds before the gold standard increase in blood pressure. Additionally, integrated SKNA features in the frequency domain quantified nerve activity and low frequency components were found to be dominant during AD, providing another parameter that could be included in an AD detection system to improve accuracy. In humans, SKNA may be used to alert patients of the onset of AD, allowing caretakers to respond quickly and make necessary changes to decrease the severe effects of AD.</p>