No description available.

Cancer (CA) is the second leading cause of death in the United States preceded only by cardiovascular disease (CVD). Over the past 30 years, the 5-year survival rate for all cancers combined has increased by more than 20%. This improved survival rate is due to early diagnosis and advances in treatment involving a multimodality treatment approach that includes radiotherapy [RT] with about half of all CA patients receiving some type of RT sometime during the course of their treatment. Cardiotoxicity is one of the most important adverse reactions of RT and leads to a meaningful risk of CVD-related morbidity and mortality. Radiotherapy-related cardiotoxicity is a heterogeneous clinical syndrome characterized by symptoms related to impaired cardiac function due to radiation-injury to one or more cardiac structures. Furthermore, the relative risk of CVD increases with increasing incidental radiation dose to the heart. There is not a unified consensus on the definition of CA-related cardiotoxicity although most trials have focused on changes in resting systolic function, and/or development of cardiac symptoms.Commonly used tools to assess cardiac function are insensitive to minor injury hence subtle changes may go unnoticed for many years. Cardiotoxicity definitions should include a dynamic functional assessment of the CV system. This may allow detection of latent CV abnormalities before the precipitous decline of resting myocardial function or the development of CV symptomology that may impact quality of life. Cardiopulmonary exercise testing (CPET) including measurement of peak oxygen consumption (VO2) is the gold standard for the assessment of cardiorespiratory fitness (CRF). Cardiorespiratory fitness is a strong, independent predictor of mortality, CVD-related mortality, HF-related morbidity and mortality, CA-related mortality and may be involved in the pathophysiologic link between anti-CA related treatments and the increased risk of late CVD events. Emerging evidence indicates CRF may be reduced in CA survivors and have utility to detect subclinical cardiotoxicity, but this has not been evaluated in CA survivors treated with RT with significant heart involvement. This dissertation consists of one literature review and one comprehensive paper that will examine the ability of CPET to detect subclinical cardiotoxicity.

Because of the aerobic nature of cellular metabolism in mammalian organisms, a continuous supply of oxygen is necessary to maintain normal physiological function. As organisms age, their metabolic rates generally decline and there are accompanying alterations in the structure and function of the microcirculation, as this part of the cardiovascular system is especially important for oxygen exchange. The overall Oxygen Transport System can be considered as being composed of two complementary components: one for Oxygen Demand and one for Oxygen Supply. The purpose of the current work is to describe the age-dependent changes in both oxygen demand and oxygen supply at the level of the microcirculation, using intravital microscopic observations of the rat spinotrapezius muscle, along with optical techniques to delineate the structural, hemodynamic and oxygenation variables needed to characterize the Oxygen Transport System in this tissue. A summary of the findings is that basal oxygen consumption gradually declined with age (from 2 to 12 months) and there were corresponding decreases in tissue blood flow, blood hemoglobin concentration and capillary surface area for oxygen exchange, so that oxygen supply and demand were generally well-matched.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Migraines are recurrent debilitating headaches that predominately afflict young women. The pathophysiology of migraines is still not well understood but is related to neurovascular dysfunction. Meningeal blood vessel dilation, extravasation of pro-inflammatory cytokines and activation of trigeminal afferent neurons promote migraine generation. Serotonin (5-HT) is an endogenous vasoactive peptide with diverse physiology. In meningeal blood vessels, serotonin causes vasoconstriction, however in coronary arteries, serotonin causes both vasodilation and vasoconstriction. In diseased coronary arteries, with impaired endothelial function, vasoconstriction predominates. Selective meningeal blood vessel serotonin agonists, termed ‘triptans’, have become the therapy of choice for migraine headaches. However, due to their constrictive effects on the coronary vasculature, triptans are not recommend in patients with known coronary artery disease, patients with greater than one coronary artery risk factor or patients with atherosclerotic cardiovascular disease risk (ASCVD) greater than ten percent. Triptan associated chest pain is a well-known phenomenon. Age, hypertension, dyspepsia, and Raynauds phenomenon are associated with triptan associated chest pain. Hypertension is the strongest risk factor for triptan associated chest pain in males. Although triptan associated chest pain is assumed to be cardiovascular due to its constrictive effect on the coronary vasculature, only a few cases of myocardial infarction, with documented ST elevation and/or troponin elevation, have been reported. Herein we report the case of a male patient with inferolateral ST elevation myocardial infarction, within minutes of receiving subcutaneous sumatriptan for migraine headache. The patient had a normal echocardiogram and electrocardiogram prior to sumatriptan use, and a normal cardiac catheterization afterwards.

Introduction: The purpose of this study was to identify mentoring practices of new faculty members in Commission on Accreditation for Respiratory Care (CoARC) accredited respiratory care programs in the U.S. and to identify the perceptions of program directors regarding the observed impact of program mentoring practices. Methods: The method for the study was quantitative non-experimental survey research. The survey instrument was an electronic questionnaire titled Respiratory Care Faculty (RCF) Mentoring Survey. The 25-item survey was divided into three dimensions: mentoring practices, mentor/mentee relationship, and perceptions of the impact of new faculty mentoring. Of the 410 possible program director participants, 126 (30%) responded to the survey. Data from the survey were used to analyze three primary research questions on four independent variables (12 total research questions). Results: Testing of the null hypotheses associated with the 12 research questions resulted in three significant findings and 9 findings that were not significant. Significant findings included female program directors reported greater opportunities for mentoring within their programs and greater levels of expectation concerning mentoring as compared to male program directors. Program directors from associate degree programs also reported a higher level of expectation concerning mentoring than program directors in bachelor’s degree programs. There was overwhelming agreement regarding the potential impact and benefit of mentoring new faculty to improve job performance, reduce turnover, improve job satisfaction, and organizational commitment. Conclusion: The results of this study may benefit administrators and educators in respiratory care in efforts to support new faculty who possibly feel underprepared or overwhelmed in the new role. Because other allied health fields of study are similar in nature to respiratory care, the findings of the study could have potential implications across a range of health-related professions.

Glia, whose name derives from the original Greek word, meaning “glue,” have long been understood to be cells that play an important functional role in the nutritive and structural support of the central nervous system, yet their full involvement has been historically undervalued. Despite the strong evidence that glial reactions to cellular debris govern the health of the nervous system, the specific properties of damaged axonal debris and the mechanisms by which glia sense them, morphologically adapt to their presence, and initiate phagocytosis for clearance, have remained poorly understood. The work presented in this thesis was aimed at addressing this fundamental gap in our understanding of the role for glia in neurodegenerative processes. I demonstrate that the cellular machinery responsible for the phagocytosis of apoptotic cell corpses is well conserved from worms to mammals. Draper is a key component of the glial response machinery and I am able to show here, for the first time, that it signals through Drosophila Shark, a non-receptor tyrosine kinase similar to mammalian Syk and Zap-70. Shark binds Draper through an immunoreceptor tyrosine-based activation motif (ITAM) in the Draper intracellular domain. I show that Shark activity is essential for Draper-mediated signaling events in vivo, including the recruitment of glial membranes to axons undergoing Wallerian degeneration. I further show that the Src family kinase (SFK) Src42A can markedly increase Draper phosphorylation and is essential for glial phagocytic activity. Therefore I propose that ligand-dependent Draper receptor activation initiates the Src42A-dependent tyrosine phosphorylation of Draper, the association of Shark and the subsequent downstream activation of the Draper pathway. I observed that these Draper-Src42A-Shark interactions are strikingly similar to mammalian immunoreceptor-SFK-Syk signaling events in myeloid and lymphoid cells. Thus, Draper appears to be an ancient immunoreceptor with an extracellular domain tuned to modified-self antigens and an intracellular domain that promotes phagocytosis through an ITAM domain-SFK-Syk-mediated signaling cascade. I have further identified the Drosophila guanine-nucleotide exchange factor (GEF) complex Crk/Mbc/dCed-12, and the small GTPase Rac1 as novel modulators of glial clearance of axonal debris. I am able to demonstrate that Crk/Mbc/dCed-12 and Rac1 function in a non-redundant fashion with the Draper pathway to promote a distinct step in the clearance of axonal debris. Whereas Draper signaling is required early during glial responses, promoting glial activation and extension of glial membranes to degenerating axons, the Crk/Mbc/dCed-12 complex functions at later stages of glial response, promoting the actual phagocytosis of axonal debris. Finally, many interesting mutants have been identified in primary screens for genes active in neurons that are required for axon fragmentation or clearance by glia, and genes potentially active in glia that orchestrate clearance of fragmented axons. The further characterization of these genes will likely unlock the mystery surrounding “eat me” and “find me” cues hypothesized to be released or exposed by neurons undergoing degeneration. Illuminating these important glial pathways could lead to a novel therapeutic approach to brain trauma or other neurodegenerative conditions by providing a druggable means of inducing early attenuation of the glial response to injury down to levels less damaging to the brain. Taken together, my combined work identifies new components of the glial engulfment machinery and shows that glial activation, phagocytosis of axonal debris, and the termination of glial responses to injury are genetically separable events mediated by distinct signaling pathways.

The 'exponential peeling' technique has been applied to minute ventilation and tidal volume transients occurring after the abrupt removal of 7,6 and 5% CO2 in inspired air. These transients, in many cases, were found to be composed of three exponential components, each contributing to the total ventilatory response and each having individual time responses. Gelfand and Lambertsen (1973) have attributed these components to the peripheral chemoreceptors as a group and to two central chemoreceptors. Statistical analysis to determine the constancy of the contribution of the three components over the the range of CO2 values studied showed that, although the values for each at the different stimulus levels were not significantly different, the great subject-to-subject variation in the data precluded a firm conclusion about the constancy of the components. Because of a number of considerations it was concluded that exponential peeling of respiratory transients following abrupt removal of CO2 inhalation is not a satisfactory way to approach the problem of the numbers, relative contributions and time responses of the various receptor groups comprising the respiratory controller.