Dissertations / Theses on the topic 'Heart disease in the newborn'

A dor ocasiona uma série de alterações sistêmicas que afetam o desenvolvimento do recém-nascido (RN), em particular, os submetidos à cirurgia cardíaca, além de acarretar alterações hemodinâmicas que podem comprometer sua sobrevivência. O objetivo do estudo foi caracterizar a população de neonatos submetidos a cirurgias cardíacas e descrever as práticas de controle da dor implementadas no primeiro pós-operatório. Estudo descritivo, transversal realizado na Sociedade Hospital Samaritano de São Paulo. Os dados foram obtidos de prontuários médicos de RN submetidos à cirurgia cardíaca, internados entre julho de 2001 e dezembro de 2005. Os registros sobre a avaliação da dor e intervenção medicamentosa para o alívio da dor no primeiro pós-operatório foram analisados. Dentre quarenta e dois RN submetidos a cirurgias cardíacas no período estudado, 30 atenderam aos critérios de inclusão e constituíram a casuística do estudo. A maioria dos RN nasceu a termo, pesava 2.500g ou mais na data do procedimento cirúrgico e foi submetida à cirurgia na primeira semana de vida. Foram identificados 24 diferentes diagnósticos de cardiopatias congênitas e 14 tipos de intervenções cirúrgicas, corretivas ou paliativas, no grupo estudado. Dentre 30 prontuários, foram identificados registros de avaliação de dor em 24 (80,0%). A avaliação por meio da escala NIPS foi anotada em 17 (56,7%) prontuários e em 15 (50,0%) verificou-se registro de comportamentos e alterações nos parâmetros fisiológicos indicativos de dor. Dos RN avaliados, 17 (56,7%) apresentaram registro de ocorrência de dor no primeiro pós-operatório. A maioria, 29 (96,7%), recebeu analgesia farmacológica: 24 (80,0%) RN receberam citrato de fentanil contínuo, 5 (16,7%) RN, dipirona intermitente, 5 (16,7%) RN, citrato de fentanil contínuo e dipirona intermitente, 1 (3,3%) RN recebeu citrato de fentanil contínuo e morfina intermitente. As doses administradas variaram amplamente. Foram também utilizados sedativos associados aos analgésicos: 12 (40,0%) RN receberam midazolan contínuo, 5 (16,7%) RN, midazolan intermitente, 1 (3,3%), besilato de cisatracúrio contínuo, 1 (3,3%) cloridrato de clorpromazina contínuo e 1 (3,3%) propofol intermitente Os resultados evidenciam não haver uniformidade e padronização na avaliação da dor pós-operatória e nos tipos e doses de fármacos utilizados para o controle da dor pós-operatória dos RN submetidos a cirurgias cardíacas no serviço estudado.
Pain causes several systemic alterations that affect the newborn’s development, specially the ones who underwent cardiac surgery. Besides, hemodynamic alterations related to pain can put their lives into risk. The aim of the study was to characterize pain control practices in newborns who underwent cardiac surgery. This is a cross-sectional and descriptive study performed in Sociedade Hospital Samaritano of São Paulo. The data were collected from the medical reports of the newborns who underwent cardiac surgery from July 2001 to December 2005. The records related to pain assessment and pharmacological treatment in the first post-operative day were analyzed. From 42 newborns who underwent cardiac surgery during the period studied, 30 of them were in accordance with the criteria of inclusion. Most of the neonates were term and their weights were 2.500 grams or more on the date of the surgery that was mostly performed in the first week of life. In the studied group, it was identified 24 different diagnoses of congenital heart deffects and 14 types of corrective or palliative surgical interventions. From the 30 medical reports, records of pain assessment were found in 24 of them (80.0%). The evaluations taken by using the NIPS were written in 17 medical reports (56.7%) and in 15 of them (50.0%) it was verified records of behavior and physiological parameters alterations that indicate pain. From the newborns evaluated, 17 (56.7%) presented records of pain in the first day post-surgery. 29 neonates (96.7%) received analgesics, as it follows: continuous fentanyl citrate, 24 newborns (80.0%); intermittent dipyrone, 5 (16.7%); continuous fentanyl citrate and intermittent dipyrone, 5 (16.7%) and fentanyl citrate and intermittent morphine, 1 (3.3%). The doses given to the neonates were very different. 12 (40.0%) newborns received the sedative midazolam by continuous infusion with analgesics. 5 (16.7%) neonates received intermittent midazolam, 1 (3.3%) received continuous cisatracurium besylate, 1 (3.3%) received continuous chlorpromazine hydrochloride and 1 (3.3%) received intermittent propofol. The results showed that there is no pattern and uniformity of pain assessment after surgery, neither of the types and doses of drugs used for pain control of the newborns who underwent cardiac surgery in the service that was studied.

A system of 32 first-order differential equations is formulated and solved for the LP model using a fourth-order adaptive Runge-Kutta solver. The output pressure and flow waveforms obtained from the LP model are imposed as boundary conditions on the CFD model. Coupling of the two models is done through an iterative process where the parameters in the LP model are adjusted to match the CFD solution. The CFD model domain is a representative HLHS anatomy of an infant after undergoing the Hybrid Norwood procedure and is comprised of the neo-aorta, pulmonary roots, aortic arch with branching arteries, and pulmonary arteries. The flow field is solved over several cardiac cycles using an implicit-unsteady RANS equation solver with the k-epsilon turbulence model.; Hypoplastic left heart syndrome (HLHS) is a complex cardiac malformation in neonates suffering from congenital heart disease and occurs in nearly 1 per 5000 births. HLHS is uniformly fatal within the first hours or days after birth as the severely malformed anatomies of the left ventricle, mitral and aortic valves, and ascending aorta are not compatible with life. The regularly implemented treatment, the Norwood operation, is a complex open heart procedure that attempts to establish univentricular circulation by removing the atrial septum (communicating the right and left ventricle), reconstructing the malformed aortic arch, and connecting the main pulmonary artery into the reconstructed arch to allow direct perfusion from the right ventricle into the systemic circulation. A relatively new treatment being utilized, the Hybrid Norwood procedure, involves a less invasive strategy to establish univentricular circulation that avoids a cardiopulmonary bypass (heart-lung machine), deliberate cardiac arrest, and circulatory arrest of the patient during the procedure. The resulting systemic-pulmonary circulation is unconventional; blood is pumped simultaneously and in parallel to the systemic and pulmonary arteries after the procedure. Cardiac surgeons are deeply interested in understanding the global and local hemodynamics of this anatomical configuration. To this end, a multiscale model of the entire circulatory system was developed utilizing an electrical lumped parameter model for the peripheral or distal circulation coupled with a 3D Computational Fluid Dynamics (CFD) model to understand the local hemodynamics. The lumped parameter (LP) model is mainly a closed loop circuit comprised of RLC compartments that model cardiac function as well as the viscous drag, flow inertia, and compliance of the different arterial and venous beds in the body.
ID: 030423155; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Thesis (M.S.)--University of Central Florida, 2011.; Includes bibliographical references (p. 59-61).
M.S.
Masters
Mechanical, Materials, and Aerospace Engineering
Engineering and Computer Science

Heart failure patients have dysfunction of the cardiac conduction system that contributes to a high burden of arrhythmias including atrial fibrillation and sudden cardiac death. Heart failure has been associated with the inflammatory response, but it is unknown if inflammation is playing a role in the remodelling of the cardiac conduction system in heart failure. Inflammation has been shown to be present in the myocardium from failing hearts and it is known to have detrimental effects on cardiac function, inducing fibrosis, remodelling of ion channels and even arrhythmias. However, the effect of inflammation on the cardiac conduction system has not been investigated. The aims of this study were to determine if there is an increase of pro-inflammatory cytokines and inflammatory cells in the cardiac conduction system in heart failure. In addition, to identify if there is possible inflammation-associated fibrosis and apoptosis in the cardiac conduction system in heart failure. To test these aims, three models of heart failure were used: a rat model of pulmonary arterial hypertension, a rabbit model of congestive heart failure and a rat model of myocardial infarction. In the rat model of pulmonary arterial hypertension there was a bradycardia, a prolongation of the QT interval, and an increase in the atrioventricular and ventricular refractory periods, suggesting electrical remodelling in these animals. The rats with pulmonary arterial hypertension displayed an increase in pro-inflammatory cytokines such as interleukins 1β and TGFβ in the right side of the heart, including the sinoatrial node and right Purkinje fibres of the cardiac conduction system. In addition, in these areas, there was an increase in components of the extracellular matrix, including fibronectin, collagen I and vimentin. Histology revealed regions of non-myocyte nuclei, only in the right ventricle of the rats with pulmonary arterial hypertension. Immunohistochemistry demonstrated patches of CD68 and vimentin expression (markers for macrophages and fibroblasts, respectively) in the right side of the heart in these animals. TUNEL staining also revealed an increase in apoptosis in the right side of the heart. In the rabbit model of congestive heart failure, the region most affected by inflammation was the right atrium, while few changes were measured in the ventricles or cardiac conduction system. Although these results are surprising, it is suggested that the atria could be more sensitive to the physical stretch produced in this model. In the rat model of myocardial infarction, there were regions of non-myocyte nuclei in the border zone. This region also had increases in pro-inflammatory and fibrosis markers. In conclusion, this work has presented the novel finding that there can be inflammation in the cardiac conduction system in heart failure. This could be contributing to the arrhythmias seen in heart failure patients. This could possibly lead the way to anti-inflammatories as a possible novel therapeutic for heart failure patients.

4 pp.
Heart disease, or cardiovascular disease (CVD), includes stroke and coronary heart disease, which are serious disorders of the heart and blood vessel system. Heart disease is the leading cause of illness and death in North American women. This publication addresses what kind of heart diseases affect women and how to live the heart-healthy way.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.
Includes bibliographical references (leaves 69-71).
Heart rate variability (HRV), the beat-to-beat fluctuation of the heart rate, is a non-invasive test that measures the autonomic regulation of the heart. Assessment of HRV has been shown to predict the risk of mortality in patients after an acute myocardial infarction. Recently, the Krieger lab at MIT developed genetically engineered double knockout (dKO) mice that develop coronary artery disease accompanied by spontaneous myocardial infarctions and die at a very young age. This thesis investigated whether HRV could function as a prognostic indicator in the dKO mouse. A novel method for estimating physiological state of the mouse from the electrocardiogram using an innovative activity index was developed in order to compare HRV variables at different times while controlling for physiologic state. Traditional time and frequency domain variables were used to assess the prognostic power of HRV. Results have shown that none of the HRV variables were helpful in predicting mortality in the dKO mice. Mean heart rate showed some prognostic power, but it was not consistent in all the dKO mice. Finally, the activity index developed in this thesis provided a reliable metric for activity in mice as validated by a camera with motion detection.
by Laurence Zapanta.
S.M.

Gap junctions are clusters of transmembrane channels, composed of connexins (Cx), that facilitate electrical and chemical communication between the cytoplasmic compartments of contiguous cells. Three connexins are expressed in cardiac myocytes, Cx40, Cx43 and Cx45. Targeted deletion of these connexin genes in mice results in cardiac malformations and conduction abnormalities. From this background, the question arises as to whether connexins play a role in human congenital heart disease. Atrial and ventricular tissue samples were studied from patients undergoing cardiac surgery. Immunoconfocal microscopy and western blot analysis of atrial tissue revealed that expression of CX40 and CX43 in children and adults with congenital heart disease is the same as that in the normal adult atrium, irrespective of the underlying malformation. Normal adult ventricular working myocytes express only CX43. Study of control ventricular samples in children confirmed that, as in adults, CX43 only is expressed. However, immunoconfocal microscopy of samples from patients with right ventricular outflow obstruction (tetralogy of Fallot and double chambered right ventricle) revealed that in addition to CX43, CX40 is also highly expressed. Expression is heterogeneous and CX40 is eo-localised with CX43. Quantitative western blot analysis showed that up to 10% of the total connexin expressed in these samples is CX40. As patients re-operated following previous repair (with markedly different underlying haemodynamics) still demonstrated high CX40 expression in the working myocardium, these results suggest that a lack of normal CX40 repression during development leads to heart malformations . . Gap junction channels formed from each connexin isofonn have distinctive biophysical properties. Connexin eo-expression further alters these properties. To investigate the functional consequences of the connexin eo-expression patterns observed in the ventricular samples, in vitro cell models were used. Intercellular communication was assessed using cell-to-cell Lucifer Yellow dye transfer in an inducible RLE cell line and conducjion properties were studied in an atrial myocyte (HL-l) cell line. The findings are consistent with the idea that altered function arising from abnormal embryonic connexin expression is a contributor to some types of human cardiac malformation.

Congenital Heart Disease (CHD) is the leading non-infectious cause of death among children less than one year. CHD is genetically heterogeneous, but analysis of large multi-generational families has led to the identification of a number of genes for CHD. In this project I investigated the molecular genetic basis of CHD in a large Kuwaiti family with clinically diagnosed truncus arteriosus. Using a homozygosity mapping approach I identified a region of interest on chromosome 8p21. I proceeded to sequence candidate genes in this region. One of the novel genes identified was predicted to be the human homolog of mouse Nkx2.6, a gene encoding a homeobox transcription factor expressed in the sinus venosa and the myocardium of the outflow tract in the developing mouse heart. Sanger sequencing identified a Phel51Leu mutation which segregated with disease in the family. Next I investigated whether mutations in Nkx2.6, or the related gene Nkx2.5, were a common cause of type I truncus arteriosus in 12 unrelated individuals. However I found no mutations, suggesting the pattern of inheritance in this phenotype is likely to be complex and potentially multifactorial. Finally I investigated the molecular genetic basis of another congenital heart defect known as Patent Ductus Arteriosus (PDA) in a multigenerational Kuwaiti family with six affected members. A condition known as Char Syndrome is characterized by a combination of major features one of which is PDA and can be caused by mutations in the TFAP2B gene which encodes the Transcription Factor AP-2 Beta. I therefore hypothesised that mutations in TFAP2B may also be responsible for PDA in the Kuwaiti family. I identified a predicted splice site variant in this gene that segregated with disease status. A full clinical history and physical examination confirmed that no affected members of this family have any of the remaining features of Char Syndrome suggesting that mutations in TFAP2B can also cause isolated PDA.

Rheumatic Heart Disease remains one of the most neglected cardiac conditions in children and young adults around the world. The pathogenesis is complex and remains elusive, and the clinical characteristics vary around the world. This thesis concentrates on different aspects of the disease in Egypt, where it is known to have a high incidence. The methodology included epidemiological studies in school children in Aswan and investigation of RHD in a population with history of RF, using newly developed echocardiographic criteria. Concomitantly, the pattern of immune response in RF and RHD was determined in serum and excised valves. In this series RF presents in children and young adults, as well as adults, (0.2-44 years, 10.69 ± 6.24) with polyarthritis being the most common clinical presentation (87.9%) and recurrences of RF being very common (98.2%). RHD affected 23 in 1000 school children in Aswan with over 90% of the cases being subclinical and developed in up to 69.2% of the individuals with history of RF, predominantly as mitral regurgitation. Risk factors for the development and severity of RHD were shown to be low disease awareness, non-compliance to penicillin prophylaxis or a regimen of longer than 15-days. Resistance to antibiotic regimens, including Penicillin and Vancomicin seems to lead to development and recurrences of RF in Egypt. This series showed the presence of immune activation and ongoing immunological reaction in an apparently quiescent phase of the disease with distortion of normal valvular architecture, histology and composition. This work has served to define the epidemiology, pattern of disease, immune reponse and predisposing factors in a population with no previous data, also contributing to the improvement of the echocardiographic diagnostic criteria. Standardization of the criteria will allow comparison of prevalence in different areas and improve case detection.

Using mean telomere length as a marker of biological age, I show that: 1. Subjects with premature myocardial infarction (MI) have significantly shorter telomeres than age-sex matched, healthy, controls. The mean telomere length in MI subjects was similar to controls almost 11 years older. 2. Healthy young adult children of families with a strong history of premature MI have shorter telomeres than age matched children of families without such a history. 3. Shorter telomere lengths are associated with increase risk of subsequent CHD events in a prospective study. This analysis was carried out on samples collected in the West of Scotland Coronary Prevention Study (WOSCOPS). This randomised blinded trial was designated to examine the benefits of statin treatment on preventing CHD and showed a 30% reduction of events in those treated with pravastatin. Interestingly, my analysis showed that this benefit of statin is only seen in those subjects at higher risk of CHD based on their telomere length.;As the final part of the thesis I carried out a quantitative linkage trait (QTL) analysis in sib-pairs in an attempt to identify genetic loci regulating telomere length. I report the mapping of a major QTL on chromosome 12 that determines almost 50% of the inter-individual variation in mean telomere length.;These findings support a novel "telomere" hypothesis of CHD. They indicate that telomere biology is intimately linked to the genetic aetiology and pathogenesis of CHD. Specifically, the findings suggest that (i) those individuals born with shorter telomeres may be at increased risk of CHD (ii) rather than individual genes, a more global structural property of the genetic material may explain the familial basis of CHD (iii) variation in telomere length may explain, in part, the variable age of onset of CHD. The findings provide several new avenues for future research.

This study explored infants' immediate and residual responses to holding and rocking, and how these responses relate to previously proposed mechanisms to explain long term benefits found when infants are repeatedly exposed to tactile and vestibular stimulation. This form of stimulation has been proposed to increase infants' ability to control and organize l) their behavioral state, 2) their arousal and autonomic functioning, or 3) that there is no clear relationship between immediate responses and long term benefits. Behavioral state and heart rate were collected on 40 infants who were randomly assigned to either a control group where infants were briefly repositioned twice but otherwise lay undisturbed for 90 minutes or an experimental group where infants were held and rocked for 30 minutes during the middle of a 90-minute observation. Results of analyses showed that, when infants were held and rocked they 1) displayed a lower Heart Rate Mean and Standard Deviation, 2) displayed a lower Mean Heart Rate During Active Sleep, 3) spent less time in a FussCry State, 3) were less likely to cry continuously, and 4) displayed nominally Smoother State Transitions and greater Stability Within States. Following the cessation of the rocking stimulus infants in the Experimental Group l) displayed a lower Mean Heart Rate, 2) displayed a lower Mean Heart Rate while in a Quiet Alert State, 3) were more likely to spend some time in a Quiet Sleep State, and 4) were less likely to cry continuously. In addition, all infants displayed Smoother State Transitions and greater Stability Within States during the first 30 minutes than during the final 30 minutes of the observation. Finally, across the 90-minute observation, the infants who were not rocked spent progressively more time in a Quiet Alert State, whereas infants who were rocked spent less time in a Quiet Alert State. The results were the most consistent with the hypothesis that the mechanism leading to both the immediate and residual effects of the stimulation was an increase in control and organization of infants’ arousal and autonomic functioning.
Ph. D.

Mortality due to structural heart disease (SHD) remains high despite advances in clinical therapies. The aim of this thesis is to elucidate how structural remodeling in heart disease may lead to the development of potentially life threatening arrhythmias. This objective was advanced by the combined use of mathematical modelling and an experimental model of myocardial infarction (MI). The computer model was used to investigate possible electrical effects of tissue remodelling associated with SHD. Heterogeneous discontinuities resembling patchy fibrosis were incorporated into a 2D array of coupled myocytes with uniform electrical properties. It was shown that structural discontinuities alone can alter dynamic instability and provide a rate-dependant substrate for electrical reentry. This challenges the wide-spread notion that dynamic instability of this kind is due to changes in cellular electrical properties. Experimental studies were carried out in sheep with healed reperfusion MI. Intramural electrical activation in the infarct border zone (BZ) was recorded with a high density mapping array. Novel techniques were developed that enable the spread of activation in this region to be reconstructed in 3D at higher resolution than has previously been possible. Heart structure was also reconstructed in 3D using magnetic resonance imaging and serial histology. Intracardiac left ventricular mapping was carried out simultaneously. The BZ substrate was characterised by systematic intramural pacing. This confirmed that activation delay, consistent with tortuous electrical pathways, is the origin of apparently slow conduction in the BZ. Stimulus-site specific, low-level activation in the BZ was followed by uniform propagation around the infarct boundary at relatively normal conduction velocities. Electrical activity in the intramural BZ was recorded during induction and maintenance of ventricular tachycardia (VT). BZ activation delays were amplified during VT induction and in some cases contributed substantially to the cycle length during VT. For the first time, complex intramural activation patterns were tracked through the BZ during reentry. In general, local intramural and endocardial activation patterns were non-stationary during VT despite relatively monomorphic limb-lead electrocardiograms. This signifies a heterogeneous substrate capable of supporting multiple arrhythmic circuits.

Plasma natriuretic peptide concentrations rise in response to either atrial or ventricular wall stretch and have been found to be useful in the diagnosis and assessment of patients with congestive cardiac failure. Although previous studies have suggested that plasma natriuretic peptides may offer some prognostic information in patients with valvular heart disease, it is unclear whether concentrations reflect disease severity and how plasma concentrations vary across different valve lesions. The aim of this research was to identify the factors that affect natriuretic peptide releases in valvular heart disease (VHD) and to investigate whether natriuretic peptides can be used in clinical practice to identify those patients who may benefit from early intervention. Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in patients with normal left ventricular (LV) systolic function and isolated VHD (mitral regurgitation, MR, n=33; aortic regurgitation, AR, n=39; aortic stenosis, AS, n=34; mitral stenosis, MS, n=30), and age and sex matched controls (n=39) immediately prior to exercise stress echocardiography. Peptide levels were compared against age and sex matched controls and against markers of severity for each valve lesions and across different valve lesions. Compared to controls, patients with all types of VHD had elevated plasma BNP concentrations [(MR median 35(inter quartile range 23-52), AR 34(22-45), AS 31(22-60), MS 58(34-90); controls 24(16-33) pg/mL; p < 0.01 for all]. LV end diastolic volume index varied by valve lesion; [MR (mean ± standard deviation 77±14), AR (91±28), AS (50±17), MS (43±11), controls (52±13) mL/m2; p < 0.0001]. There were no associations between LV volume and BNP. Left atrial (LA) area index varied [MR (18±4cm2/m2), AR (12±2), AS (11±3), MS (19±6), controls (11±2); p < 0.0001], but correlated with plasma BNP concentrations: MR (r=0.42,p=0.02), MS (r=0.86,p < 0.0001), AR (r=0.53,p=0.001), AS (r=0.52, p=0.002). Higher plasma BNP concentrations were associated with increased pulmonary artery pressure and reduced exercise capacity. Despite adverse cardiac remodelling, 81(60%) patients had a BNP concentration within the normal range. In patients with MS BNP was strongly associated with left atrial area index (r=0.86; p < 0.0001) and a BNP level of greater than 2 times the upper limit of normal identified patients who fulfilled guideline criteria for intervention (Area under the curve (AUC) 0.87 [0.74,0.99], p =0.006) and lower exercise capacity (AUC 0.82 [0.67,0.97]; p=0.004). In AR patients significant remodelling could occur whilst BNP remained within the normal range and in general BNP appeared less useful in assessing disease severity. However raised levels of BNP was associated with more severe AR as assessed by left ventricular outflow tract:AR Jet area ratio (r=0.43 p=0.0007). AR patients with an abnormal BNP had signs of early LV dysfunction on exercise with a lower LV longitudinal strain rate post exercise compared to AR patients with a normal BNP (0.68±0.31 vs. 1.06±0.45 1/sec; p=0.02). In MR patients, higher plasma BNP concentrations were associated with larger left atrial area index (r=0.42, p=0.02), higher pulmonary artery pressure (r=0.53, p=0.002) and a lower exercise time (r=-0.60, p=0.0002). BNP was not associated with any marker of left ventricular size or function in MR. These findings suggest that despite significant LV remodelling, plasma BNP concentrations are often normal in patients with VHD. Consequently, plasma BNP concentrations should be interpreted with caution when assessing patients with VHD. However natriuretic peptide levels offer complementary information to the standard assessment of patients with VHD and an unexplained finding of an elevated BNP in an otherwise asymptomatic patient should prompt further investigation.

Fifty percent of the diagnosed cases of coronary heart disease in the United States are of unknown etiology. This study proposed that five personality traits— achievement, dominance, aggression, succorance and Critical Parent—differentiate individuals with coronary heart disease manifestations. The ultimate goal of this research was to formulate a predictive profile of at-risk individuals of developing coronary heart disease. Cardiac rehabilitation units' participants from across the United States were recruited as subjects. Randomly selected cardiac rehabilitation units were sent an initial letter inquiring whether their staff would be willing to participate in the study by administering the instruments to their participants. Eight units from each of the 50 states were contacted. A total of fourteen units agreed to participate. One hundred sixty-nine subjects completed the Demographic Data Questionnaire and the Adjective Check List. Five scale scores, representing the five personality differentials, were analyzed. Comparison of the male subject population (n=135) and the male normative population (n=198) revealed no significant differences in terms of the five traits. Comparison of diagnostic subgroups of the subject population also revealed no significant differences. It was concluded that the subject population did not differ significantly from the normative population in terms of the five traits assess by the instrument used. The goal of a predictive profile was not realized due to this lack of findings.
Master of Science
incomplete_metadata

Introduction: Some past breast cancer radiotherapy regimens led to an increased risk of death from heart disease. Although heart dose from breast cancer radiotherapy has generally reduced over the past few decades, there may still be some cardiac risk. Estimation of future risk for women irradiated today requires both measurement of their cardiac dose and dose-response relationships, which depend on cardiac dosimetry of past regimens, in conjunction with long-term follow-up data. Methods: Virtual simulation and computed tomography 3-dimensional treatment planning on a representative patient were used to estimate mean heart and coronary artery doses for women irradiated since 1950 in 71 randomised trials in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview. Patient-to-patient variability in cardiac dose was assessed. Heart and coronary artery doses were also calculated for breast cancer radiotherapy regimens used since the 1950s in Sweden. Cardiac doses from contemporary (year 2006) radiotherapy were assessed for 55 patients who received tangential breast cancer irradiation at a large UK radiotherapy centre. The maximum heart distance (i.e. the maximum distance between the anterior cardiac contour and the posterior tangential field edges) was measured for the left-sided patients, and its value as a predictor of cardiac doses assessed. Results: Mean heart dose for women irradiated in the EBCTCG trials varied from <1 to 18 Gray, and mean coronary artery dose from <1 to 57 Gray. Patient-to-patient variability was moderate. Mean heart dose for women irradiated in Sweden since the 1950s varied from <1 to 24 Gray, and mean coronary artery dose from <1 to 46 Gray. Heart dose from tangential irradiation has reduced over the past four decades. However, mean heart dose for left-sided patients irradiated in 2006 was 2 Gray and around half of them still received >20 Gray to parts of the heart and left anterior descending coronary artery. For these patients, maximum heart distance was a reliable predictor of cardiac doses. For the other patients, mean heart dose varied little and was usually less than 2 Gray. Conclusions: Cardiac doses from breast cancer radiotherapy can be estimated reliably and are now available for use in deriving dose-response relationships in the EBCTCG data and in a Scandinavian case-control study. Cardiac dose has reduced over the past four decades. Therefore the cardiac risk is also likely to have reduced. Nevertheless, for some patients, parts of the heart still receive >20 Gray in the year 2006.

In coronary artery disease,. resting electrical and mechanical function of the left ventricle may vary according to different presentations. Stress or exercise in these patients results in electrical disturbances, which may havc mechanical consequences. The objectives ofthis thesis were: I) to assess the effect of the presence and location of Q wave myocardial infarction on left ventricular segmental mechanical function and identify patterns ofdisturbances. 2) to study the acute implications of induction of localised myocardial infarction at the proximal ventricular septum on ventricular performance. 3) to determine the effect of pharmacological stress on left and right ventricular behaviour in patients with coronary artery disease. AIl patients were studied by Doppler echocardiography using conventional measurements, as well as detailed assessment of long axis function and 12 lead surface EeG's. The foHowing groups ofpatients were studied: a). 72 patients with old Q wave MI; 35 anterior and 37 inferior. b) 54 patients with old anterior MI; 39 Q wave and 15 non-Q wave MI. c) 20 symptomatic patients with hypertrophic obstructive cardiomyopathy before and after non-surgical septal reduction therapy. d) . 27 patients with coronary artery disease, at rest and during dobutamine stress to assess left ventricular fune:tion. e) 33 patients with triple coronary artery disease at rest and at peak dobutamine stress to assess right ventricular function. The normal septal Q wave was' absent in 94% of anterior and 8% of inferior MI patients. Long axis amplitude and shortening and lengthening velocities were globaIly reduced in anterior and inferior myocardial infarction and the onset of shortening and lengthening were delayed by 30-40ms and 20-30 ms respectively in the two patient groups. Post ejection ~hortening was localised to the septum in the majority of patients with anterior myocardial infarction, but was generalised in patients with inferior infarction. 1) The normal septal Q wave was absent in 10% of control subjects and in 46% of patients with non-Q wave myocardial infarction. Q wave anterior MI was associated with a scarred septum and dilated LV cavity. Long axis amplitude was not different from normal in non-Q wave-infarction, but its onset ofshortening and lengthening was delayed by 20ms. Post ejection shortening occurred more frequently in Q wave infarction (76%) compared with non-Q wave infarction (21 %). These .abnormalities were localised to the left rand septal sites in non-Q wave infarction in contrast to their global distribution in Q wave infarction. . 2) Induction of localised upper septal myocardial infarction with alcohol resulted in broadening of the QRS (by 35ms), RBBB in 80% of patients, development of reduced septal long axis amplitude, and accentuated post ejection shortening at the septal long axis site. 3) In contrast to controls, dobutamine stress results in progressive broadening of QRS duration and prolongation of the QTc interval in patients with coronary artery disease, with corresponding reductions in long axis amplitude of motion and peak lengthening .velocity. 4) In patients with triple vessel coronary disease, dobutamine stress results in right ventricular long axis ischaemic disturbances similar to those seen on the left. Failure ofright ventricular long axis amplitude to increase by 2 mm was 88% specific for detecting right ventricular ischaemic dysfunction, which also correlated with the attenuated cardiac output at peak stress r= 0.56, p