Dissertationen zum Thema „Maternal blood pressure“

Observational studies on the association between birth weight and adult blood pressure provide suggestive evidence that exposures during fetal development can have lasting impacts on health. The effect of maternal nutrition during pregnancy on offspring blood pressure has been demonstrated in animal models, but data from cohort studies in humans have proven inconclusive. The follow-up of randomised controlled trials of nutritional supplementation during pregnancy can add high quality data to this research field; this thesis focuses on the effects in three separate trials. Protein energy supplementation provided to pregnant women in rural Gambia was unrelated to offspring blood pressure at 11-17 years old (n=1267). Again in The Gambia, maternal calcium supplementation compared to placebo was also unrelated to offspring blood pressure at 5-10 years old (n=350). In rural Bangladesh there was no effect of maternal food or multiple micronutrient supplementation on offspring systolic blood pressure at 4.5 years old (n=2335). The micronutrient intervention was also unrelated to offspring diastolic blood pressure, but there was evidence that an early invitation to enter a governmental food supplementation programme was associated with marginally lower diastolic blood pressure: 0.58mmHg (95% Cl: 0.06,1.11; P: 0.03). In this setting, randomisation to receive counselling to promote exclusive breast feeding was not associated with offspring blood pressure at 4.5 years of age and none of the interventions were associated with offspring kidney function, assessed as ultrasound-obtained volume and glomerular filtration rate calculated from plasma Cystatin C. These data suggest that the maternal diet during pregnancy, at least those aspects of intake that can be altered during supplementation trials, may not be directly relevant for the determination of offspring blood pressure. Nutritional exposures during other stages of the life course may prove to be more important

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IntroduÃÃo: hà uma recomendaÃÃo internacional formal de que à preciso e possÃvel predizer prÃ-eclÃmpsia para a obtenÃÃo de resultados maternos e neonatais mais favorÃveis. Objetivos: avaliar a acurÃcia das caracterÃsticas maternas e pressÃo arterial mÃdia como preditores de prÃ-eclÃmpsia no primeiro trimestre gestacional; elaborar um algoritmo para prediÃÃo de prÃ-eclÃmpsia na populaÃÃo local; e comparar a acurÃcia do modelo de prediÃÃo elaborado com os sugeridos pelo National Institute of Clinical Excellence (NICE) e American College of Obstetricians and Gynecologists (ACOG). MÃtodos: trata-se de estudo metodolÃgico de desenvolvimento tecnolÃgico, realizado a partir de dois estudos de coortes desenvolvidos entre agosto de 2009 e janeiro de 2014 no Hospital Geral de Fortaleza (HGF) e no Hospital Distrital Gonzaga Mota de Messejana (HDGMM). A amostra foi constituÃda por 733 gestantes entre 11 e 13 semanas, das quais 55 desenvolveram prÃ-eclÃmpsia (PE), sendo 21 PE prÃ-termo e 34 PE termo. Foram obtidos dados das caracterÃsticas maternas (CM) e pressÃo arterial mÃdia (PAM). AnÃlises de regressÃo logÃstica determinaram a contribuiÃÃo dos testes para a prediÃÃo precoce de PE. A taxa de detecÃÃo (TD) para 5 e 10% de falsos positivos (TFP) e as Ãreas sob a curva ROC (AUC) foram obtidas. Resultados: variÃveis como PE anterior, histÃria familiar de PE, IMC e PAM se mostraram Ãteis como parÃmetros preditivos e foram considerados no cÃlculo do risco. Para PE total, a AUC do modelo CM+PAM foi 0,787 (IC95% 0,756-0,816), a TD foi de 22% e 44% para uma TFP de 5% e 10% respectivamente. Para PE prÃ-termo, a AUC do modelo CM+PAM foi 0,842 (IC95% 0,814-0,868), a TD foi de 43% e 67% para uma TFP de 5% e 10% respectivamente. Os valores de AUC (0,562 para ACOG e 0,657 para NICE) para PE prÃ-termo compromete a acurÃcia desses modelos de prediÃÃo de PE para esta populaÃÃo. ConclusÃo: a associaÃÃo de CM + PAM tem bom poder preditivo para prediÃÃo de PE no primeiro trimestre gestacional na populaÃÃo em estudo.
Introduction: According to a formal international recommendation, it is necessary and possible to predict pre-eclampsia to obtain more favourable maternal and neonatal results. Objectives: To assess the accuracy of maternal characteristics and average blood pressure as predictors of pre-eclampsia in the first trimester; to create an algorithm that can predict pre-eclampsia in the local population; and to compare the accuracy of the created prediction model with the models suggested by the National Institute of Clinical Excellence (NICE) and the American College of Obstetricians and Gynaecologists (ACOG). Methods: This is a methodological and technological development study based on two cohort studies conducted between August 2009 and January 2014 in the Fortaleza General Hospital (HGF) and the Gonzaga Mota de Messejana District Hospital (HDGMM). The sample consisted of 733 women who were between 11 and 13 weeks pregnant, of which 55 developed pre-eclampsia (PE). Of these women, 21 had preterm PE and 34 had term PE. Data were obtained from maternal characteristics (MC) and average arterial pressure (MAP). Logistic regression analysis determined the contribution of the tests in predicting early PE. The detection rate (DR) for 5 and 10% of false positives (FPR) and the areas under the ROC curve (AUC) were obtained to measure accuracy. Results: Variables such as prior PE, family history of PE, BMI, and MAP proved useful as predictive parameters and were considered in the calculation of risk. For total PE, the AUC of the MC+MAP model was 0.787 (CI 95% 0.756 - 0.816), and the DR was 22% and 44% for a FPR of 5% and 10%, respectively. For preterm PE, the AUC of the MC+MAP model was 0.842 (CI 95% 0.814 - 0.868), and the DR was 43% and 67% for a FPR of 5% and 10%, respectively. The AUC values (0.562 for ACOG and 0.657 for NICE) for preterm PE undermine the accuracy of these PE prediction models for this population. Conclusion: The association of MC+MAP can appropriately predict PE in the first trimester of pregnancy among the studied population.

Modern societies face an increasing prevalence of non-infectious, chronic diseases associated with modern lifestyle. In particular, cardiovascular (and cerebrovascular) disease remains the leading cause of morbidity and mortality, according to the World Health Organization, the American Heart Association and the Australian National Heart Foundation. Our diet, typically high in fat and sugar is one of the main causes, leading to what has been described as an obesity epidemic. Such diets are associated with diabetes, high cholesterol and high blood pressure: all major risk factors for cardiovascular disease. However, there appears to be an even more insidious threat to the cardiovascular health of the next generation. Recent evidence demonstrates that maternal obesity during pregnancy increases the risk of cardiovascular disease in the offspring in later life (McMillen and Robinson 2005). This is termed developmental origins of disease, and is now the subject of research that has expanded exponentially in the last 15 years. It is unclear whether maternal obesity increases cardiovascular risk in the offspring because of the obesity itself or because of mother’s diet, which is the likely cause of the obesity. Moreover, the pathophysiological changes that predispose the adult offspring to cardiovascular disease are unclear. This thesis exams 2 main questions: (1) Does a Western “fast food” diet, high in fat and sugar, during pregnancy, cause high blood pressure in the offspring, even when the mother is not obese? (2) Do the offspring exposed to a perinatal high fat/high sugar diet show altered cardiovascular responses to psychological stress? This may partly explain the pathophysiology of hypertension in the offspring, in the form of neurogenic hypertension. Sachini K. Jayaratne IX The contents of this thesis are as follows. In Chapter 1, the literature surrounding the hypothesis of the Developmental Origins of Health and Disease are reviewed, with a focus on programmed hypertension. Possible causative factors are discussed, including renal and vascular dysfunction, but with the primary focus on a neurogenic cause. The role of increased reactivity to stress is considered in the context of stress-induced causes of cardiovascular disease, and a brief overview of current methodologies used in research to assess autonomic function is given. Finally, the role of oxidative stress in hypertension is reviewed. Chapter 2 presents the results of a study that investigated in rats the impact of a non-obesogenic maternal high fat-high sucrose (HFS) diet on offspring blood pressure and cardiovascular responses to psychological stress. Dams were placed on a “W estern fast food diet” containing 21% (w/w) fat, 34% (w/w) sucrose and 19% protein for 4 weeks prior to conception, during gestation and lactation. The offspring were then weaned and placed on a normal chow diet. Control dams were kept on a normal chow diet for the entire period. At approximately 9-12 months age, the offspring were implanted with blood pressure telemetry probes and blood pressure, heart rate and derived indices of autonomic control (heart rate variability, blood pressure variability and spontaneous baroreflex gain) were measured at rest and in response to air jet (AJS) and restraint stress (RS). The results showed that adult HFS programmed offspring were hypertensive at rest and had increased blood pressure reactivity to AJS. Male, but not female offspring also showed increased reactivity to RS. The results demonstrated that a maternal HFS diet during the perinatal period can cause hypertension in the offspring in later Sachini K. Jayaratne X life, and that this can occur even if the dam is of normal body weight. The manuscript will be submitted to the Journal of Physiology for publication. Chapter 3 compared c-Fos expression in key cardiovascular control regions in the brainstem and hypothalamic following AJS (considered a mild psychological stressor) and RS (considered a more severe stress). Adult male Sprague Dawley rats were subjected to either AJS or RS. After 2 hours post-stress, rats were deeply anaesthetized with pentobarbital sodium (100 mg/kg) and perfused transcardially with physiological saline, followed by 4% paraformaldehyde (w/v) in 0.1M phosphate buffer. Brains were removed, sectioned and reacted immunohistochemically for Fos IgG. RS caused greater overall Fos expression than AJS with regional increases in the dorsomedial hypothalamus (DMH), hypothalamic perifornical area (PeF), lateral periaqueductal grey (lPAG), ventrolateral PAG (vlPAG), locus coeruleus, parabrachial complex and rostral ventrolateral medulla. A differential pattern of Fos expression was noted particularly in the PAG, with AJS predominately activating dorsolateral and lPAG, while RS predominately activating lPAG and vlPAG. The results confirm that RS is a more potent stressor than AJS. In addition, the results support the argument that RS includes a more physical, or interoceptive, component of stress than AJS. This manuscript has been submitted to Neuroscience Letters for publication. Chapter 4 examines the hypothesis that HFS programming of hypertension may have a neurogenic cause due to increased oxidative stress in key brainstem regions of cardiovascular control. HFS programmed offspring were produced as in Chapter 2. The rats were euthanized and the ventrolateral medulla, PAG and DMH/PeF were rapidly collected on ice. The tissue underwent assays to test levels of protein carbonylation, a common marker of oxidative stress, Sachini K. Jayaratne XI and glutathione, an important antioxidant that prevents oxidation of protein side chains. In a separate series of rats, cardiovascular function at rest and in response to AJS was examined following treatment with the antioxidant Tempol in the drinking water for 4 weeks. The results showed that there was increased protein carbonyls and decreased glutathione in the DMH/PeF of HFS offspring, but not in the PAG or RVLM. Tempol treatment abolished the hypertension and cardiovascular reactivity these offspring. These results are the first to demonstrated that oxidative stress plays an important role in the aetiology of high blood pressure and increased cardiovascular reactivity to stress in a non-obesogenic HFS model of developmental hypertension. This manuscript will be submitted to the Journal of Physiology for publication. In a preliminary study, Chapter 5 compares Fos expression, as a marker of neuronal activation, in cardiovascular control regions in HFS and control rats following AJS and RS. HFS and control offspring were produced as described above and at 9 months age male rats were subjected to either AJS or RS. At 2 hours post-stress test, the rats were deeply anaesthetized and perfused with 4% paraformaldehyde. Brains were removed, sectioned and processed for Fos immunohistochemistry. The results showed that in HFS programmed rats, RS produced increased Fos expression in the paraventricular nucleus and reduced Fos expression in the dorsomedial PAG, compared to control rats. Following AJS there was reduced Fos expression in the lateral PAG in HFS offspring than controls. These results provide preliminary data to elucidate the neuroanatomical substrate that underlies the difference in cardiovascular responses to stress in HFS programmed offspring.

Includes bibliographical references (leaves 228-257). Aims to determine the impact of maternal undernutrition during late gestation and during the periconceptional and gestational periods on fetal growth, fetal blood pressure and the fetal hypothalamo-pituitary adrenal axis in the sheep.

>Magister Scientiae - MSc
Blood pressure and heart rate is known to increase during smoking. These effects are specifically associated with nicotine while the other components of tobacco smoke seem to be of minor importance. It is becoming increasingly clear that fetal nicotine exposure, through transfer of nicotine via the placenta, has numerous consequences that is detrimental to the health of the fetus and that these effects may last into adulthood or perhaps even manifest itself later in life. In this study, we investigated the effects of maternal nicotine exposure during pregnancy and lactation on the blood pressure of the male offspring. A preliminary study indicated that the female offspring do not become hypertensive. We were particularly interested to determine whether hypertension in the offspring could be prevented or attenuated by vitamin C (an antioxidant) therapy. When confirmed to be pregnant, female Wistar rats were divided into four groups. The control group (group 1) received saline (1ml/day, s.c), the animals in group 2 received nicotine (1mg/kg/day in ml, s.c), group 3 animals received a combination of saline (1 ml/day s.c.) and vitamin C (1g/l in drinking water) and the animals in group 4 received a combination of nicotine (1mg/kg/day, s.c) and vitamin C (1g/l in the drinking water) during pregnancy and lactation. At weaning eight animals from group 2 received vitamin C in the drinking water (1g/l) until the end of the experiment. Blood pressure and body weight were measured every two weeks for 5 months. Blood samples were collected, and serum prepared at 3 weeks and at 5 months for biochemical analysis. Total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD) assays were determined at 3 weeks; TAC was also measured at five months. After 5 months, the animals were sacrificed and abdominal aorta was excised for histological (H and E staining) and IHC (AGE) evaluation. From the data generated in this study, it was evident that maternal nicotine exposure during pregnancy and lactation increased blood pressure of male offspring but not female offspring. Exposure to nicotine during pregnancy and lactation significantly increased systolic blood pressure from 115±4.6 mm Hg in the first month to 147±6.1 mm Hg at five months (P<0.05), diastolic blood pressure was increased from 84±3.4 mm Hg in the first month to 110±7.2 mm Hg at 5 months (P<0.05) and MAP was increased from 94.8±3.8 mm Hg in the first month to 121±6.4 mm Hg at 5 months. Interestingly the MAP of the nicotine group was normal during the first two months. HR was similar in all groups at 5 weeks and 5 months. Maternal vitamin C supplementation in rats exposed to nicotine during pregnancy and lactation did not prevent development of hypertension of the offspring (MAP=121±6.4 mm Hg in the nicotine group vs 113.4±1.7 mmHg in the nicotine and vitamin C group, P>0.05). Supplementation with vitamin C in the drinking water after weaning significantly reduced blood pressure of the offspring (MAP=121±6.4 mm Hg vs 97.6±2.9 mm Hg respectively, P<0.05). No significant difference was found in any of the biochemical assays. Maternal nicotine exposure during pregnancy and lactation leads to alteration in aorta structure as evaluated by H and E staining. Structural alterations include protrusion of the intima and irregular arrangement of the vascular smooth muscle cells (VSMC) in the tunica media. Maternal vitamin C supplementation and vitamin C supplementation after weaning did not prevent the structural alteration of the aorta. Immunohistochemistry (IHC) indicated that the accumulation of AGE's in the nicotine group was stronger than in the control group. In conclusion, we show for the first time that hypertension induced by maternal nicotine exposure can be reversed after weaning by supplementation with vitamin C, an antioxidant.

Background: In Nigeria, there is an escalating incidence of hypertension, its complications and other cardiovascular risks, likely to have their origins in early life. Malaria is still hyperendemic, with pregnant women at increased risk, with associated consequences of maternal anemia and high rates of delivering low birth-weight babies. Aims and Hypothesis: In this study, we have tested the hypothesis that malaria in pregnancy will not only enhance the risk of small birth size and poor infant growth, but will also generate higher blood pressures in infancy and beyond. We also tested the hypothesis that metabolic markers in pregnant mothers affected by malaria would relate to infant birth size. Thus the aims of this project were: 1) to define relationships between the type of malaria exposure and birth size, 2) to characterize the association between maternal and cord metabolic biomarkers and birth size on the background of prenatal malaria exposure and 3) to examine the effect prenatal malaria exposure on first year growth and whether higher blood pressure (BP) is generated. Methods: Healthy pregnant women were recruited and followed at Adeoyo Maternity Hospital, Ibadan. Anthropometric, BP, and biomarkers (lipids, glucose, insulin and TNFα) measurements were obtained in the mothers at booking. Birth size and growth at 3 and 12 months along with biomarkers (as above) and IGF-I measures in cord blood were assessed in the infants. Blood films for malaria parasites were taken throughout pregnancy including delivery and in all babies. Women were grouped to distinguish between the timing of malaria parasitaemia (either during pregnancy only or during pregnancy and at delivery) and the severity of malaria infection (low vs high parasite load). At birth, 436 mother-baby pairs were measured. 467 maternal samples were obtained for metabolic profile and 187 cord blood samples. 318 babies were all followed from birth to 3 and 12 months. Results: Malaria parasitaemia was found in 48% of the women, associated with younger maternal age, being primigravid and a lower haematocrit. Babies of mothers with high parasitaemia through pregnancy had the smallest birth growth parameters compared with those without malaria (weight, length, and head circumference were smaller by 300g, 1.1cm and 0.7cm respectively, all p≤0.005) but their systolic BP (SBP) and diastolic BP (DBP) adjusted for weight were higher than those with low parasitaemia by 1.7 and 1.4 mmHg/kg respectively. SBPs were lowest in babies of mothers with malaria at delivery implying an acute effect on the babies’ circulation. Mothers with malaria had significantly lower lipids (except triglycerides) but higher TNFa, effect not seen in cord blood. Cord IGF-I was significantly lower in babies whose mothers had malaria. Significant determinants of birth size were maternal total cholesterol, LDL- cholesterol, insulin, malarial status and cord insulin and IGF-I. Babies exposed to maternal malaria remained smaller at 1 year, most marked in boys, whose SBP adjusted for weight at 3 and 12 months was higher than those not exposed. Change in SBP over the first year was greater in boys than girls while the change in girls was greater in those exposed to maternal malaria than those not exposed (18.7 vs 12.7 mmHg, 95% CI 1-11, p=0.02). 11% of boys ( > twice expected) had BP >95th percentile (hypertensive, US criteria) of whom 68% had maternal malaria exposure. Gender, maternal malaria exposure and weight change were all independently associated with increased change in BP to 1 year. Conclusion: Intrauterine exposure to malaria appears not only to have an important impact on birth size but also gender-dependent effects on growth and changes in infant BP. These findings have potential implications for cardiovascular health in sub-Saharan Africa and may contribute to the global burden of hypertension.

Preeclampsia is a placental-related disorder characterized by generalized endothelial activation. Vascular predisposition is associated with the occurrence of preeclampsia and the recurrence risk is substantial. Onset of preeclampsia is preceded by placental hypo-perfusion, and placental over-production of vasoconstrictive agents might explain symptoms such as hypertension and proteinuria. Preeclampsia is associated with the birth of small-for-gestational-age (SGA) infants. The trajectory of postnatal growth in SGA-born children is described as catch-up, but it is unclear whether prenatal preeclampsia is independently associated with postnatal growth. The objectives were: firstly, to study the association between partner change and prior miscarriages on the occurrence of preeclampsia and SGA; secondly, to study postnatal growth in children prenatally exposed to preeclampsia; and thirdly, to address the association between blood pressure (BP) changes during pregnancy and risks of preeclampsia and SGA. Population-based cohort studies were performed with information from the following registers: Swedish Medical Birth Register, Uppsala Mother and Child Database and Stockholm-Gotland Obstetric Database. Associations were estimated with logistic and linear regression analyses, with adjustments for maternal characteristics, including body mass index, pre-gestational diseases and socioeconomic factors. The results were, firstly, that partner change was associated with preeclampsia and SGA birth in the second pregnancy but depended on the outcome of the first pregnancy, and that a history of recurrent miscarriages was associated with increased risks of preeclampsia and SGA. Secondly, prenatal exposure to preeclampsia was associated with increased offspring growth in height during the first five years. This association was also seen in children born with normal birth weight for gestational age. Thirdly, pre-hypertension in late gestation and elevated diastolic BP from early to mid-gestation were both associated with SGA birth. Further, women with pre-hypertension in early gestation without lowered diastolic BP until mid-gestation seemed to represent a risk group for preeclampsia. To conclude, the importance of previous pregnancy outcomes in the antenatal risk evaluation was highlighted. Secondly, the results imply that postnatal growth trajectory is related to maternal preeclampsia, in addition to SGA. Thirdly, the association between BP changes within a normal range and SGA may challenge the clinical cut-off for hypertension in pregnancy.

Background. Maternal obesity and physical inactivity have been identified as correlates of overweight and obesity and physical inactivity in older preadolescents; however, no study has explored this relationship in Hispanic preadolescents. Furthermore, the relation between maternal physical activity (PA) and blood pressure (BP) in Hispanic preadolescents has not been examined. Purpose. This study aimed to assess the associations between Hispanic mothers’ PA and body mass index (BMI) and their preadolescents’ PA, screen time, BP, and BMI. Methods. Data of 118 mother-child (aged 2–10 years) dyads enrolled in a crosssectional study of metabolic syndrome in Hispanic preadolescents at a community health center in Johnson City, TN were used. Parent and child questionnaires were used to ascertain mothers’ BMI and PA and preadolescents’ PA and screen time.

Hypertension (HTN) is a major risk factor for cardiovascular diseases including stroke, coronary heart disease (CHD), chronic renal failure, peripheral vascular disease, myocardial infarction, congestive heart failure and premature death. The prevalence of HTN in Scotland is very high and although a high proportion of the patients receive antihypertensive medications, blood pressure (BP) control is very low. Recommendations for starting a specific antihypertensive class have been debated between various guidelines over the years. Some guidelines and HTN studies have preferred to start with a combination of an antihypertensive class instead of using a single therapy, and they have found greater BP reductions with combination therapies than with monotherapy. However, it has been shown in several clinical trials that 20% to 35% of hypertensive patients could not achieve the target BP, even though they received more than three antihypertensive medications. Several factors were found to affect BP control. Adherence and persistence were considered as the factors contributing the most to uncontrolled hypertension. Other factors such as age, sex, body mass index (BMI), alcohol intake, baseline systolic BP (SBP), and the communication between physicians and patients have been shown to be associated with uncontrolled BP and resistant hypertension. Persistence, adherence and compliance are interchangeable terms and have been used in the literature to describe a patient’s behaviour with their antihypertensive drugs and prescriptions. The methods used to determine persistence and adherence, as well as the inclusion and exclusion criteria, vary between persistence and adherence studies. The prevalence of persistence and adherence have varied between these studies, and were determined to be high in some studies and low in others. The initiation of a specific antihypertensive class has frequently been associated with an increase or decrease in adherence and persistence. The tolerability and efficacy of the initial antihypertensive class have been the most common methods of explaining this association. There are also many factors that suggest a relationship with adherence and persistence. Some factors in previous studies, such as age, were frequently associated with adherence and persistence. On the other hand, relationships with certain factors have varied between the studies. The associations of age, sex, alcohol use, smoking, baseline systolic blood pressure (SBP) and diastolic BP (DBP), the presence of comorbidities, an increase in the number of pills and the relationship between patients and physicians with adherence and persistence have been the most commonly investigated factors. Most studies have defined persistence in terms of a patient still taking medication after a period of time. A medication possession ratio (MPR) ≥ 80 has been used to define compliance. Either of these terminologies, or both, have been used to estimate adherence. In this study, I used the same definition for persistence to identify patients who have continued with their initial treatment, and used persistence and MPR to define patients who adhered to their initial treatment. The aim of this study was to estimate the prevalence of persistence and adherence in Scotland. Also, factors that could have had an effect on persistence and adherence were studied. The number of antihypertensive drugs taken by patients during the study and factors that led to an increase in patients being on a combination therapy were also evaluated. The prevalence of resistance and BP control were determined by taking the BP after the last drug had been taken by persistent patients during five follow-up studies. The relationship of factors such as age, sex, BMI, alcohol use, smoking, estimated glomerular filtration rate (eGFR), and albumin levels with BP reductions for each antihypertensive class were determined. Information Services Division (ISD) data, which includes all antihypertensive drugs, were collected from pharmacies in Scotland and linked to the Glasgow Blood Pressure Clinic (GBPC) database. This database also includes demographic characteristics, BP readings and clinical results for all patients attending the GBPC. The case notes for patients who attended the GBPC were reviewed and all new antihypertensive drugs that were prescribed between visits, BP before and after taking drugs, and any changes in the hypertensive drugs were recorded. A total of 4,232 hypertensive patients were included in the first study. The first study showed that angiotensin converting enzyme inhibitor (ACEI) and beta-blockers (BB) were the most prescribed antihypertensive classes between 2004 and 2013. Calcium channel blockers (CCB), thiazide diuretics and angiotensin receptor blockers (ARB) followed ACEI and BB as the most prescribed drugs during the same period. The prescription trend of the antihypertensive class has changed over the years with an increase in prescriptions for ACEI and ARB and a decrease in prescriptions for BB and diuretics. I observed a difference in antihypertensive class prescriptions by age, sex, SBP and BMI. For example, CCB, thiazide diuretics and alpha-blockers were more likely to be prescribed to older patients, while ACEI, ARB or BB were more commonly prescribed for younger patients. In a second study, 4,232 and 3,149 hypertensive patients were included to investigate the prevalence of persistence in the Scottish population in 1- and 5-year studies, respectively. The prevalence of persistence in the 1-year study was 72.9%, while it was only 62.8% in the 5-year study. Those patients taking ARB and ACEI showed high rates of persistence and those taking diuretics and alpha blockers had low rates of persistence. The association of persistence with clinical characteristics was also investigated. Younger patients were more likely to totally stop their treatment before restarting their treatment with other antihypertensive drugs. Furthermore, patients who had high SBP tended to be non-persistent. In a third study, 3,085 and 1,979 patients who persisted with their treatment were included. In the first part of the study, MPR was calculated, and patients with an MPR ≥ 80 were considered as adherent. Adherence rates were 29.9% and 23.4% in the 1- and 5-year studies, respectively. Patients who initiated the study with ACEI were more likely to adhere to their treatments. However, patients who initiated the study with thiazide diuretics were less likely to adhere to their treatments. Sex, age and BMI were different between the adherence and non-adherence groups. Age was an independent factor affecting adherence rates during both the 1- and 5-year studies with older patients being more likely to be adherent. In the second part of the study, pharmacy databases were checked with patients' case notes to compare antihypertensive drugs that were collected from the pharmacy with the antihypertensive prescription given during the patient’s clinical visit. While 78.6% of the antihypertensive drugs were collected between clinical visits, 21.4% were not collected. Patients who had more days to see the doctor in the subsequent visit were more likely to not collect their prescriptions. In a fourth study, 3,085 and 1,979 persistent patients were included to calculate the number of antihypertensive classes that were added to the initial drug during the 1-year and 5-year studies, respectively. Patients who continued with treatment as a monotherapy and who needed a combination therapy were investigated during the 1- and 5-year studies. In all, 55.8% used antihypertensive drugs as a monotherapy and 44.2% used them as a combination therapy during the 1-year study. While 28.2% of patients continued with treatment without the required additional therapy, 71.8% of the patients needed additional therapy. In all, 20.8% and 46.5% of patients required three different antihypertensive classes or more during the 1-year and 5-year studies, respectively. Patients who started with ACEI, ARB and BB were more likely to continue as monotherapy and less likely to need two more antihypertensive drugs compared with those who started with alpha-blockers, non-thiazide diuretics and CCB. Older ages, high BMI levels, high SBP and high alcohol intake were independent factors that led to an increase in the probability of patients taking combination therapies.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Introdução: A colheita da cana-de-açúcar precedida pela queima noturna expõe trabalhadores a altas concentrações de poluentes que somados aos efeitos da jornada de trabalho acarreta o aumento do trabalho cardiorrespiratório, ocasionando alterações multissistêmicas. Apesar das grandes evidências dos efeitos deletérios da exposição ao material particulado (MP), ainda tem sido dada pouca atenção aos efeitos das exposições ocupacionais a longo prazo. Objetivos: Esta dissertação teve como objetivos: avaliar os sintomas nasais, parâmetros hemodinâmicos e perfil inflamatório nasal e sistêmico de cortadores de cana-de-açúcar expostos à queima de biomassa ao longo de uma safra canavieira. Métodos: Foram avaliados no artigo I 41 indivíduos e no artigo II 45 indivíduos, cortadores de cana-de-açúcar do gênero masculino de uma usina de açúcar e álcool, divididos em grupos de acordo com o hábito tabagístico. Para avaliação da frequência e intensidade dos sintomas nasais foi aplicado questionário de sintomas respiratórios e para avaliação dos parâmetros hemodinâmicos foi registrado valores de pressão arterial (PA), frequência cardíaca (FC) e respiratória (f). Para análise do perfil inflamatório nasal (IL-6, IL-10 e IL-4) foi coletado amostras de lavado nasal e para análise de perfil inflamatório sistêmico (TNF-α, IL-6, IL-8 e IL-10) e contagem total de monócitos e neutrófilos foram realizados coletas de sangue venoso. As avaliações ocorreram durante a pré-safra (março), meio da safra (julho) e final da safra (outubro) de 2014. Resultados: Durante o meio da safra houve aumento significativo da frequência e intensidade dos sintomas espirros, congestão nasal além do aumento de relatos na dificuldade para respirar. Em relação a PA, FC e f todos os participantes apresentaram alterações significativas durante a safra. Na análise do perfil inflamatório houve alterações significativas a nível sistêmico para IL-8 e contagem de neutrófilos que obteve aumento no meio da safra seguido de um decréscimo ao final safra. Conclusões: Conclui-se que cortadores de cana-de-açúcar apresentam aumento na frequência e intensidade de sintomas nasais assim como alterações nos parâmetros hemodinâmicos principalmente no meio da safra. Além disso, todos os cortadores apresentaram diminuição de IL-8 e número de neutrófilos a nível sistêmico devido a exposição repetida ao MP.
Introduction: The harvest of sugarcane preceded by night burning exposes workers to high concentrations of pollutants added to the effects of the workday causes increased cardiorespiratory work, causing alterations multisystem. Despite the great evidences of the deleterious effects of exposure to particulate matter (PM), still has been given little attention to the effects of long-term occupational exposures. Objective: This Master’s thesis aimed to evaluated nasal symptoms, hemodynamic parameters and nasal and systemic inflammatory profile of sugarcane cutters exposed to biomass burning along a sugarcane harvest. Methods: Were evaluated in article I 41 individuals and in article II 45 individuals, sugarcane cutters, male cutters from a sugar and alcohol plant divided into groups according to smoking habit. To evaluate the frequency and intensity nasal symptoms was questionnaire applied of respiratory symptoms and to evaluate the hemodynamic parameters was registered blood pressure (BP), heart rate (HR) and respiratory (f). For analysis of the nasal inflammatory profile (IL-6, IL-10 and IL-4) was collected nasal lavage and for analysis of the systemic inflammatory profile (TNF-α, IL-6, IL-8 and IL-10) and total count monocytes and neutrophils from venous blood were performed. The evaluations occurred during the pre-harvest (March), middle of harvest (July) and end of harvest (October) in 2014. Results: During the middle of harvest there was a significant increase in the frequency and intensity of symptoms sneezing, nasal congestion beyond the increase in reports of difficulty in breathing. In relation the BP, HR and RR all participants showed significant alterations during the harvest. For analysis of inflammatory profile there were significant changes in systemic levels for IL-8 and neutrophil counts that had an increase in middle of harvest followed by a decrease at the end of harvest. Conclusions: Conclude that sugarcane cutters have increased in frequency and intensity of nasal symptoms, as well as changes in hemodynamic parameters, mainly in the middle of harvest. In addition, all cutters showed a decrease in IL-8 and neutrophil counts at systemic level at the end of harvest due to repeated exposure to PM.
FAPESP: 2014/08029-0

Peripheral vascular grafts are used for the treatment of peripheral arterial disease and arteriovenous grafts for vascular access in end stage renal disease. The development of neo-intimal hyperplasia and thrombosis in the distal anastomosis remains the main reason for occlusion in that region. The local haemodynamics produced by a graft in the host vessel is believed to significantly affect endothelial function. Single spiral flow is a normal feature in medium and large sized vessels and it is induced by the anatomical structure and physiological function of the cardiovascular system. Grafts designed to generate a single spiral flow in the distal anastomosis have been introduced in clinical practice and are known as spiral grafts. In this work, spiral peripheral vascular and arteriovenous grafts were compared with conventional grafts using ultrasound and computational methods to identify their haemodynamic differences. Vascular-graft flow phantoms were developed to house the grafts in different surgical configurations. Mimicking components, with appropriate acoustic properties, were chosen to minimise ultrasound beam refraction and distortion. A dual-beam two-dimensional vector Doppler technique was developed to visualise and quantify vortical structures downstream of each graft outflow in the cross-flow direction. Vorticity mapping and measurements of circulation were acquired based on the vector Doppler data. The flow within the vascular-graft models was simulated with computed tomography based image-guided modelling for further understanding of secondary flow motions and comparison with the experimental results. The computational assessments provided a three-dimensional velocity field in the lumen of the models allowing a range of fluid dynamic parameters to be predicted. Single- or double-spiral flow patterns consisting of a dominant and a smaller vortex were detected in the outflow of the spiral grafts. A double- triple- or tetra-spiral flow pattern was found in the outflow of the conventional graft, depending on model configuration and Reynolds number. These multiple-spiral patterns were associated with increased flow stagnation, separation and instability, which are known to be detrimental for endothelial behaviour. Increased in-plane mixing and wall shear stress, which are considered atheroprotective in normal vessels, were found in the outflow of the spiral devices. The results from the experimental approach were in agreement with those from the computational approach. This study applied ultrasound and computational methods to vascular-graft phantoms in order to characterise the flow field induced by spiral and conventional peripheral vascular and arteriovenous grafts. The results suggest that spiral grafts are associated with advanced local haemodynamics that may protect endothelial function and thereby may prevent their outflow anastomosis from neo-intimal hyperplasia and thrombosis. Consequently this work supports the hypothesis that spiral grafts may decrease outflow stenosis and hence improve patency rates in patients.

“Overworking to death” is a phenomenon that has been noticeable in developing countries. The cause of death is mainly through ischemic strokes. While the victims’ occupations differed, they all shared a common characteristic, being positioned in a sedentary work, ranging from IT workers to doctors. This project’s aim was to develop a product that prevented or decreased the strokes that derived from sedentary overwork. This was mainly tackled by preventing one of the three causes of developing blood props, slowed blood flow. In order to gather rich data of the phenomenon, a qualitative study was conducted in China, during two months. By doing an extensive structured sampling, information rich data could be gathered during a short period of time. Data were derived from observations, questionnaires and an interview, which then was interpreted to customer needs and the final product specification. The final product became a trouser with an in built dynamic compression mechanic, that can compress the veins mostly during sitting activities, in order to prevent blood stasis. The compression mechanic works like the Chinese finger trap; compressing the calves while sitting and stretching the legs forward. It is made only out of polysaccharides fibres; cotton and corn.
"Guolaosi" eller död från överarbete är ett fenomen som i regel uppkommer bland utvecklingsländer. Dödsorsaken är huvudsakligen genom stroke. Offrens yrken varierar allt från professorer, IT-arbetare till läkare. De delar dock en sak gemensamt; att arbeta under långa perioder stillasittande. Projektets mål var att utveckla en produkt som minskar dödliga följderna av sedentära överarbete, genom att förebygga en av de tre orsakerna för att utveckla blodproppar; saktad blodström. Målgruppen var då kineser av de yrken som hade tidigare drabbats av fenomenet. För att samla informationsrika data om fenomenet genomfördes en kvalitativ studie i Kina under två månader. Genom att göra en omfattande strukturerad provtagning kunde informationsrika data samlas under en kort tidsperiod. Fältstudien bestod av observationer, frågeformulär och en intervju, som då tolkades till kundbehov och eventuellt produktspecifikationen. Den slutliga produkten kom att bli ett par byxor med en inbyggd dynamisk komprimeringsmekanism, som kan komprimera venerna under sittande aktiviteter, för att förhindra saktad blodström. Kompressionsmekanismen fungerar som den kinesiska fingerfällan. Den komprimerar blodkärlen medan personen sitter och sträcker benen framåt. Produkten är konstruerad på så sätt att den kan tillverkas endast av polysackariders tråd, från bomull och majs. Vilket är lämpligt för Kinas lokala resurser.

This thesis explores the various meanings and implications of transparency in architecture and in learning environments in particular. Architectural transparency, achieved through choice of materials and principles of formal composition, creates a diversity of relationships and can facilitate visual, conceptual, and functional clarity as well as offering simultaneous perception of different spaces. It offers a range of phenomenological qualities and so provides an opportunity to explore and complicate such dichotomies as translucency and opacity, openness and closure, and public space and private space. While celebrated throughout modern and contemporary architecture, transparency raises issues of privacy and safety even as it breaks down hierarchies and social boundaries. The research-based design of transparency in a school building necessitates careful planning to achieve a balance between the access to views, natural light, fresh air, and social interaction that transparency may bring and the continuing obligation to provide a safe, secure environment for schoolchildren.

Includes bibliographical references (leaves 228-257).
xxii, 257 leaves : ill. ; 30 cm.
Aims to determine the impact of maternal undernutrition during late gestation and during the periconceptional and gestational periods on fetal growth, fetal blood pressure and the fetal hypothalamo-pituitary adrenal axis in the sheep.
Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2001

Includes bibliographical references (leaves 228-257).
xxii, 257 leaves : ill. ; 30 cm.
Title page, contents and abstract only. The complete thesis in print form is available from the University Library.
Aims to determine the impact of maternal undernutrition during late gestation and during the periconceptional and gestational periods on fetal growth, fetal blood pressure and the fetal hypothalamo-pituitary adrenal axis in the sheep.
Thesis (Ph.D.)--University of Adelaide, Dept. of Physiology, 2001

Abstract: Background: Fetal Alcohol Syndrome (FAS), located on the severe end of a spectrum of disorders known as Fetal Alcohol Spectrum Disorders (FASDs), is one of the most detrimental, and publicized, teratogenic outcome of alcohol consumption during pregnancy within the United States. During pregnancy, alcohol that is consumed by the mother passes through the placenta and transfers to the baby via the umbilical cord. The same prenatal transference of alcohol that leads to FAS and FASDs might also be contributing to an increased likelihood of hypertension in youth. Additionally, factors such as stress influenced by familial instability, an increased likelihood of developing congenital and conotruncal heart defects, and a reduction in nephron count might be leading to an increased likelihood of hypertension in FAS-affected youth. The purpose of this study is to examine the relationship between prenatal exposure to alcohol, manifested through FAS, and hypertension in children, adolescents, and young adults. Methods: A case-control study design was incorporated to analyze the association between FAS status and hypertensions status; cases (n=165) were collected from a FAS clinical database in Atlanta, Georgia. Controls (n=177) were taken from the National Health and Nutrition Examination Survey (NHANES). Chi-square analyses were used to examine the extent to which FAS status, sex, race/ethnicity, medication use, and obesity status each relate to hypertension status. A logistic regression was performed analyzing the relationship between FAS status (y/n: independent) and hypertension status (y/n: dependent) whilst controlling for sex, race/ethnicity, medication use, and obesity status. Results: The univariate relationships between FAS status and hypertension status (OR=4.491, p<.001) as well as medication use and hypertension status (OR= 2.951, p=.002) proved to be statistically significant (p<.05). Through the regression, FAS status significantly predicted hypertension status (β = 1.646, OR = 5.184, p< .001) after accounting for sex, race/ethnicity, medication use, and obesity status. Those with a race/ethnicity categorized as either Non-Hispanic African American (β =1.259, OR = 3.523, p = .049) or Hispanic (β = 1.192, OR = 3.294, p = .061) were significantly more likely to have hypertensions than those categorized as non-Hispanic Caucasian. Conclusion: The major findings of this study suggest a significant relationship between FAS and hypertension in youth. Race/ethnicity also proved important in predicting hypertensive blood pressure readings independent of FAS diagnosis. The most obvious biological mechanism catalyzing the relationship between FAS and hypertension is prenatal alcohol exposure. Because prenatal alcohol exposure is the primary definitional and diagnostic factor of FAS, associative connectivity may exist independently between prenatal alcohol exposure and blood pressure at various levels of severity along an alcohol exposure dose-response spectrum. Further research is needed to isolate and measure the effect that prenatal alcohol exposure has on blood pressure independently of FAS as well as to assess the extent to which the risk for hypertension in alcohol-affected individuals increases with age and through the life course.

Chan, Chun Hung.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2008.
Includes bibliographical references (leaves 77-84).
Abstracts in Chinese and English.
Acknowledgment: --- p.i
摘要 --- p.ii
Abstract --- p.iv
List of Figure --- p.vi
List of Table --- p.viii
Content Page --- p.ix
Chapter Chapter 1 --- Introduction --- p.1
Chapter 1.1 --- The Difficulties --- p.1
Chapter 1.2 --- The Solution --- p.2
Chapter 1.3 --- Goal of the Present Work --- p.2
Chapter Chapter 2 --- Background and Methodology --- p.3
Chapter 2.1 --- Hypertension Situation and Problems Around the World --- p.3
Chapter 2.1.1 --- Blood Pressure Variability (BPV) --- p.4
Chapter 2.2 --- Blood Pressure Measuring Methods --- p.5
Chapter 2.2.1 --- Traditional Blood Pressure Meters --- p.6
Chapter 2.2.2 --- Limitation of Commercial Blood Pressure Meters --- p.7
Chapter 2.2.3 --- Pulse-Transit-Time (PTT) Based Blood Pressure Measuring Watch --- p.7
Chapter 2.3 --- Wearable Body Sensors Network / System --- p.8
Chapter 2.4 --- Current Status of e-Textile Garment --- p.9
Chapter 2.4.1 --- Blood Pressure Measurement in e-Textile Garment --- p.13
Chapter 2.5 --- Wearable Intelligent Sensors and System for e-Health (WISSH) --- p.15
Chapter 2.5.1 --- "Monitoring, Connection and Display" --- p.15
Chapter 2.5.2 --- Treatment --- p.16
Chapter 2.5.3 --- Alarming --- p.17
Chapter Chapter 3 --- "A h-Shirt to Non-invasive, Continuous Monitoring of Arterial Blood Pressure" --- p.18
Chapter 3.1 --- Design and Inner Structure of h-Shirt --- p.18
Chapter 3.1.1 --- Choose of e-Textile Material --- p.21
Chapter 3.1.2 --- Design of ECG Circuit --- p.23
Chapter 3.1.3 --- Design of PPG Circuit --- p.26
Chapter 3.2 --- Blood Pressure Estimation Using Pulse-Transit-Time Algorithm --- p.28
Chapter 3.2.1 --- Principal --- p.28
Chapter 3.2.2 --- Equations --- p.29
Chapter 3.2.3 --- Calibration --- p.29
Chapter 3.3 --- Performance Tests on h-Shirt --- p.30
Chapter 3.3.1 --- Test I: BP Measurement Accuracy --- p.30
Chapter 3.3.2 --- Test I: Procedure and Protocol --- p.30
Chapter 3.3.3 --- Test I-Results --- p.31
Chapter 3.3.4 --- Test II: Continuality BP Estimation Performance --- p.31
Chapter 3.3.5 --- Test II - Experiment Procedure and Protocol --- p.32
Chapter 3.3.6 --- Test II - Experiment Result --- p.33
Chapter 3.3.7 --- Test II 一 Discussion --- p.43
Chapter 3.4 --- Follow-up Tests on ECG Circuit --- p.47
Chapter 3.4.1 --- Problems --- p.47
Chapter 3.4.2 --- Assumptions --- p.48
Chapter 3.4.3 --- Experiment Protocol and Setup --- p.48
Chapter 3.4.4 --- Experiment Results --- p.53
Chapter 3.4.5 --- Discussion --- p.56
Chapter Chapter 4: --- Hybrid Body Sensor Network in h-Shirt --- p.59
Chapter 4.1 --- A Hybrid Body Sensor Network --- p.59
Chapter 4.2 --- Biological Channel Used in h-Shirt --- p.60
Chapter 4.3 --- Tests of Bio-channel Performance --- p.62
Chapter 4.3.1 --- Experiment Protocol --- p.62
Chapter 4.3.2 --- Results --- p.62
Chapter 4.4 --- Discussion and Conclusion --- p.63
Chapter Chapter 5: --- Conclusion and Suggestions for Future Works --- p.66
Chapter 5.1 --- Conclusion --- p.66
Chapter 5.1.1 --- Structure of h-Shirt --- p.66
Chapter 5.1.2 --- Blood Pressure Estimating Ability of h-Shirt --- p.67
Chapter 5.1.3 --- Tests and Amendments on h-Shirt ECG Circuit --- p.67
Chapter 5.1.4 --- Hybrid Body Sensor Network in h-Shirt --- p.67
Chapter 5.2 --- Suggestions for Future Work --- p.68
Chapter 5.2.1 --- Further Development of Bio-channel Biological Model --- p.68
Chapter 5.2.2 --- Positioning and Motion Sensing with h-Shirt --- p.69
Chapter 5.2.3 --- Implementation of Updated Advance Technology into h-Shirt --- p.69
Appendix: Non-invasive BP Measuring Device - Finometer --- p.71
Reference: --- p.77