Ultrasound imaging, a stethoscope for body composition assessment

Bone and muscle are two deeply interconnected organs and a strong relationship between them exists in their development and maintenance. The peak of both bone and muscle mass is achieved in early adulthood, followed by a progressive decline after the age of 40. The increase in life expectancy in developed countries resulted in an increase of degenerative diseases affecting the musculoskeletal system. Osteoporosis and sarcopenia represent a major cause of morbidity and mortality in the elderly population and are associated with a significant increase in healthcare costs. Several imaging techniques are currently available for the non-invasive investigation of bone and muscle mass and quality. Conventional radiology, dual energy X-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound often play a complementary role in the study of osteoporosis and sarcopenia, depicting different aspects of the same pathology. This paper presents the different imaging modalities currently used for the investigation of bone and muscle mass and quality in osteoporosis and sarcopenia with special emphasis on the clinical applications and limitations of each technique and with the intent to provide interesting insights into recent advances in the field of conventional imaging, novel high-resolution techniques and fracture risk

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes

Les valeurs anthropométriques ; mesures prédictives du risque cardio-métabolique et du syndrome métabolique au Kenya

Introduction : La prévalence mondiale des maladies cardiovasculaires et métaboliques (MCM) ainsi que du Syndrome métabolique (SM) est en constante augmentation, et ce plus drastiquement dans les pays en voie de développement. L’accumulation de gras corporel, communément estimé par des mesures anthropométriques, a été associé au SM et à un risque accru de développer des MCM. Cette relation demeure toutefois très peu étudiée parmi les populations de pays d’Afrique sub-Saharienne. Objectif: L’objectif de cette étude était d’évaluer l’association entre les mesures anthropométriques et les facteurs de risque de MCM, en plus du SM, parmi des populations adultes rurales et urbaines du Kenya. Méthodologie : Cette étude transversale comprenait 1401 participants de milieux ruraux et urbains. Les valeurs anthropométriques ont été mesurées, incluant le poids corporel, l’indice de masse corporelle (IMC), la circonférence abdominale (CA), le gras abdominal viscéral (VAT), le gras abdominal sous cutané (SAT) et le ratio de ces deux valeurs (VAT/SAT). Des valeurs de glycémies (à jeun, 2 heures post glucose), d’insuline et de lipides plasmatiques (Triglycérides, LDL-C, HDL-C, cholestérol total) ont été analysées. La résistance à l’insuline a été estimée par l’Homeostatic model assessment of insulin resistance (HOMA-IR). Des valeurs de tension artérielle systolique (TAS) et diastolique (TAD) ont été mesurées. Des analyses de régressions linéaires et logistiques multivariées ont été utilisées afin d’évaluer les forces d’association. Résultats : Les participants de milieux urbains avaient des valeurs anthropométriques et des facteurs de risques de MCM plus élevés comparativement aux participants de milieux ruraux (P<0.05 pour le poids corporel, IMC, CA, SAT et VAT/SAT) (P<0.05 pour les triglycérides, LDL-C, cholesterol total, glycémie à jeun, insuline, HOMA-IR, TAS et TAD). L’ensemble des facteurs de risques de MCM et le SM étaient positivement et significativement associés aux valeurs anthropométriques, excepté pour les valeurs de HDL-C. VAT et SAT présentaient les associations les plus fortes. Conclusion : Les valeurs anthropométriques d’accumulation du gras et particulièrement celles qui reflètent de l’obésité abdominale sont des indicateurs pertinents de la santé cardio- métaboliques des populations rurales et urbaines du Kenya.Background: The prevalence of cardio-metabolic diseases (CMD) and metabolic syndrome (MS) is drastically increasing in low and middle income countries. CMD and MS risk factors has been correlated with anthropometric measures of fat accumulation. However, very few studies have addressed by this association in rural and urban Sub-Saharan African (SSA) populations. It remains unclear which anthropometric features of fat accumulation are best associated with CMD risk factors and MS. This study aimed to investigate the association between anthropometric features, metabolic syndrome (MS) and other cardio-metabolic risk factors in a population from Kenya. Methods: In this cross-sectional study, 1,401 rural and urban Kenyan men and women were examined. Anthropometric measurements were carried out, including body weight, body mass index (BMI), waist circumference(WC), visceral and subcutaneous abdominal adipose tissue (VAT and SAT). Measures of blood glucose (FBG, 2-h OGTT), fasting plasma insulin and plasma lipids were analyzed. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Systolic and diastolic blood pressure (SBP and DBP) were measured. Adjusted multivariate linear regression analyses and adjusted multivariate logistic regression analysis were performed. Results: Urban Kenyans had significantly higher anthropometric features (p <0.05 for Weight, BMI, WC, SAT and VAT/SAT) and CMD risk factors (p <0.05 for triglycerides, LDL-C, total cholesterol, FPG, FPI, HOMA-IR, OGTT, SBP and DBP) compared to rural. CMD risk factors and MS were associated with all anthropometric features of fat accumulation, except for HDL- C levels (P<0.05) and the strongest associations were seen with VAT and SAT. Conclusions: Anthropometric measures of fat accumulation, especially features of central obesity, are relevant indicators of cardio-metabolic health in Kenyan rural and urban populations

Double blind randomized placebo-controlled trial on the effects of testosterone supplementation in elderly men with moderate to low testosterone levels: design and baseline characteristics [ISRCTN23688581]

In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men. We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60–80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety. Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. ≥ 100 cm; testosterone level (<12 versus ≥ 12 nmol/L), age (< median versus ≥ median), and level of outcome under study (< median versus ≥ median). At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m(2 )and 10.72 nmol/L, respectively

Oscillatory wall strain reduction precedes arterial intimal hyperplasia in a murine model

Cardiovascular diseases (CVD) remain the most common cause of death in the United States. Additionally, peripheral artery disease affects thousands of people each year. A major underlying cause of these diseases is the occlusion of the coronary or peripheral arteries due to arteriosclerosis. To overcome this, a number of vascular interventions have been developed including angioplasty, stenting, endarterectomies and bypass grafts. Although all of these methods are capable of restoring blood flow to the distal organ after occlusion, they are all plagued by unacceptably high restenosis rates. While the biological reactions that occur as a result of each of these methods differ, the initiating factor of both the primary atherosclerosis and subsequent failure of vascular interventions appears to be intimal hyperplasia (IH). Intimal hyperplasia is most simply defined as the expansion of multiple layers of cells internally to the internal elastic lamina of the blood vessel. This excessive cellular growth leads to arterial stenosis, plaque formation and inflammatory reactions. Despite extensive research the underlying factors that cause IH remain unclear. A quantity of research to date has implicated endothelial cell mechanosensation as the mechanism by which IH is initiated with evidence positively correlating wall shear stress with IH. Others, however, have demonstrated that changes in the stresses applied to the wall in vitro can modulate IH independent of hemodynamic shear stress. Thus, relations between wall tensile stress and IH in vivo may shed light on the underlying mechanisms of IH. Since noninvasive measurement of wall tensile stress in vivo is difficult, it is most feasible to measure oscillatory wall strain which is intimately related to wall tensile stress through the mechanical properties of the arterial wall. In this dissertation, we hypothesize that reductions in oscillatory wall strain precede the formation of intimal hyperplasia in a murine model. To test our hypothesis, we first developed a novel, high spatial and temporal resolution method to measure oscillatory wall strains in the murine common carotid artery. We validated this method both in vitro using an arterial phantom and in vivo using a murine model of abdominal aortic aneurysms. To assess relationships between strain and IH, we applied our strain measurement technique to a recently developed mouse model of IH. In this model, a suture is used to create a focal stenosis and reduce flow through the common carotid artery by 85%; resulting in proximal IH formation. Using this approach, we identified a relationship between oscillatory strain reductions and IH. Subsequent analysis demonstrated that early reductions in mechanical strain just 4 days after focal stenosis creation correlate with IH formation nearly 1 month later. Since IH is not expected to form by day 4 in this model, we went on to assess changes in gross vascular morphology at day 4. We discovered that, although strains are significantly reduced by day 4, no significant IH can be observed, suggesting that changes in wall structure are resulting in strain reductions. At day 4 post-op, we observed cellular proliferation and leukocyte recruitment to the wall without intimal hyperplasia. These studies suggest that early reductions in mechanical strain may be an important predictor of IH formation. Clinically, this relation could be important for the development of novel techniques for predicting IH formation before it becomes hemodynamically significant

Evaluation of metabolic parameters and markers of subclinical cardivascular desease in new and non-obese users of depot medroxyprogesterone acetate contraceptive

Orientador: Arlete Maria dos Santos FernandesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: As doenças cardiovasculares (DCV) estão entre as principais causas de mortalidade global. Nos Estados Unidos as taxas de mortalidade por DCV em mulheres nas faixas de idade de 35-54 anos não têm mostrado a redução esperada. O numero de mulheres nos estudos ainda é pequeno e falta conhecimento sobre o impacto na saúde cardiovascular dos ciclos gestacionais e do uso de compostos hormonais para contracepção/terapias por períodos longos. Objetivos: avaliar o metabolismo de carboidratos e marcadores de DCV em mulheres não obesas saudáveis durante o primeiro ano de uso do contraceptivo de acetato de medroxiprogesterona de depósito (AMPD). Métodos: estudo prospectivo não randomizado, comparativo, conduzido no Ambulatório de Planejamento Familiar e no Serviço de Ecografia do Departamento de Obstetrícia e Ginecologia da Faculdade de Ciências Médicas/UNICAMP, entre 02/2011 e 02/2013. Mulheres com 18-40 anos e índice de massa corporal (IMC) <30 kg/m2, recrutadas a partir de Unidades Básicas de Saúde, realizaram teste de pós-carga com 75 mg glicose via oral (OGTT). Foram incluídas aquelas que apresentaram OGTT normal e assinaram Termo de Consentimento Livre e Esclarecido. Os critérios de exclusão foram diagnóstico/antecedente de Diabete Melittus, período de aleitamento, hipertensão arterial, hiper/hipotiroidismo, insuficiência renal crônica, hirsutismo/hiperandrogenismo, Síndrome do Ovário Policístico, uso crônico de corticosteróides, antipsicóticos, tiazídicos e estatinas, antecedente de transplante de órgão, cirurgia bariátrica e omentectomia. As mulheres puderam escolher utilizar o AMPD ou o dispositivo intrauterino com cobre (DIU) e compuseram dois grupos pareados por idade (±1) e IMC (±1), seguidos durante 12 meses. Realizou-se avaliação de peso, IMC, composição corporal por densitometria (DXA), medidas da cintura, pressão arterial e ultrassonográficas da espessura da intima-media da artéria carótida e dos compartimentos de gordura abdominal (GA), dosagens séricas dos perfis glicêmico e lipídico, ácidos graxos livres, apolipoproteínas A1 e B-100, adipocinas IL-6, TN-alfa, leptina, adiponectina, PCR e cálculo do índice HOMA. Resultados: Apresentaram-se 290 mulheres, 72 com critérios para inclusão e 56 (31 grupo AMPD e 25 DIU) foram analisadas com relação ao metabolismo de carboidratos, semestralmente. O grupo AMPD mostrou elevação nos níveis séricos de insulina, HOMA, circunferência da cintura e IMC, quando comparado ao grupo DIU. Analisando-se as 30 mulheres sem resistência insulínica, o grupo AMPD mostrou aumento de triglicérides aos 12 meses em relação ao grupo DIU. Entre 37 mulheres, as medidas ultrassonográficas de GA, realizadas no basal e aos 12 meses, apresentaram forte correlação com as medidas de composição corporal e antropométricas, e com as concentrações séricas de colesterol total, LDL colesterol, APO B-100 e PCR. Conclusões: Não foram observados efeitos cardiovasculares significativos no primeiro ano de uso do AMPD nesta amostra; o aumento de triglicérides foi interpretado como variação provocada por alterações no metabolismo da glicose. HOMA, peso corporal e circunferência da cintura foram parâmetros clínicos importantes para o monitoramento das usuárias de AMPD. A ultrassonografia poderá ser ferramenta viável para identificar indivíduos com aumento de gordura corporal e risco cardiovascular; sendo necessários estudos futuros para confirmação desses resultados, padronização de locais de aferição e pontos de corte relacionados ao possível risco para DCVAbstract: One of the main causes of global death is cardiovascular disease (CVD). In the United State of America the mortality rates have not decreased as expected in women between 35 and 54 years old. In general, the studies are performed with a small number of women in the sample composition and lack knowledge about specifically female characteristics and their interaction in cardiovascular health, such as the use of hormonal contraceptives for a prolonged time. Objectives: To evaluate carbohydrate metabolism and markers of CVD in the first year of depot medroxyprogesterone acetate (DMPA) for contraceptive use. Methods: Prospective, not randomized comparative study conducted in the Family Planning Clinic and Ultrasound Unit of the Department of Obstetrics and Gynecology, University of Campinas Medical School, between 02/2011-02/2013. Women aged 18-40 years and body mass index (BMI) <30 kg/m2, recruited from Basic Health Units, performed a post-load test with 75 mg oral glucose (OGTT). Those that presented normal OGTT and agreed to participate were included in the study. The exclusion criteria were diagnosis/history of diabetes mellitus, lactation period, hypertension, hyper/hypothyroidism, chronic renal failure, hirsutism/hyperandrogenism, polycystic ovarian syndrome, chronic use of corticosteroids, antipsychotics, thiazides and statins, history of organ transplantation, bariatric surgery and omentectomy. Women were able to choose to use the DMPA or copper intrauterine device (IUD) and composed two matched groups by age (±1) and BMI (±1), followed for 12 months. Were evaluated weight, BMI, body composition (BC), waist circumference, blood pressure and ultrasound measurements of the carotid intimal medial thickness and abdominal fat compartments (AF), serum levels of lipid and glycemic profiles, free fatty acids, apolipoproteins A-1 and B-100, adipokines IL-6, TN-alpha, leptin, adiponectin, C-reactive protein (CRP) and HOMA index, at baseline and 12 months. Results: 290 women were enrolled, of which 72 met the criteria for inclusion and only 56 women (31-DMPA group and 25-IUD group) were analyzed with regard to carbohydrate metabolism at baseline and after 6 and 12 months. The DMPA group showed elevated serum levels of insulin, HOMA, waist circumference and BMI when compared to the IUD group. The analysis of 30 women without insulin resistance, diagnosed by hyperinsulemic euglycemic clamp, the DMPA group showed increase of triglycerides at 12 months when compared to the IUD group. Among 37 women, ultrasonography measurements of AF at baseline and 12 months showed a strong correlation with BC and anthropometric measurements, and serum concentrations of total cholesterol, LDL- chol, APO B-100 and CRP. Conclusions: No significant cardiovascular effects were observed in the first year of DMPA use in this sample; the increase in triglycerides was interpreted as a variation caused by changes in glucose metabolism. HOMA, body weight and waist circumference were important clinical parameters for the monitoring of DMPA users. Ultrasonography may be a viable tool to identify individuals with increased body fat and cardiovascular risk and future studies are required to confirm these results, to standardize measurement sites and cut-off points related to the possible risk for CVDDoutoradoSaúde Materna e PerinatalDoutor em Ciências da Saúde2009/ 53293-0FAPES

Systems Radiology and Personalized Medicine

Medicine has evolved into a high level of specialization using the very detailed imaging of organs. This has impressively solved a multitude of acute health-related problems linked to single-organ diseases. Many diseases and pathophysiological processes, however, involve more than one organ. An organ-based approach is challenging when considering disease prevention and caring for elderly patients, or those with systemic chronic diseases or multiple co-morbidities. In addition, medical imaging provides more than a pretty picture. Much of the data are now revealed by quantitating algorithms with or without artificial intelligence. This Special Issue on “Systems Radiology and Personalized Medicine” includes reviews and original studies that show the strengths and weaknesses of structural and functional whole-body imaging for personalized medicine

Splanchnic Metabolism and Blood Flow In Man. PET Studies with Reference to Obesity and Diabetes

Splanchnic region comprises the interaction of multiple organs, hormones and neural factors and is a critical regulator of glucose homeostasis during both postabsorptive and absorptive states. While splanchnic functions deteriorate during long-standing obesity predisposing to impaired glucose regulation and type 2 diabetes, many of the aspects of splanchnic metabolism and blood flow (BF) in health and disease are still unknown. In the present work, validation of positron emission tomography (PET) for the measurement of pancreatic and intestinal metabolism and BF in vivo was carried out and thereafter the method was applied to a total of 62 morbidly obese and 40 healthy individuals. In a set of cross-sectional and longitudinal studies glycemic control and β-cell function, splanchnic glucose and lipid metabolism, and splanchnic vascular responses to a mixed-meal, incretin infusions and glucose loading were explored before and after bariatric surgery and weight loss. Compared to healthy controls, pancreatic fatty acid (FA) uptake and steatosis were markedly increased in obese patients whereas pancreatic glucose uptake (GU) and BF were impaired. Elevated pancreatic steatosis and inadequate BF were associated with poor insulin secretion rate. In the small intestine, insulin upregulated GU nearly three-fold over the fasting values in healthy controls whereas normally glucose tolerant obese patients were unresponsive to the stimulatory effect of insulin. In lean controls and patients with type 2 diabetes, mixed-meal increased both pancreatic and intestinal BF, whereas GIP infusion decreased and increased pancreatic and intestinal BF, respectively. Bariatric surgery was followed by a prominent weight loss, increase in insulin sensitivity and β-cell function, and decrease in pancreatic FA uptake, rate of steatosis and BF. While the vascular responses of GIP were essentially similar at post-surgery when compared to pre-surgery, splanchnic vascular responses during mixed-meal were enchanced, likely as a result of rapid gastric emptying. In conclusion, pancreatic and small intestinal metabolism and BF respond to obesity and type 2 diabetes, and to metabolic changes elicited by bariatric surgery. The adequacy of pancreatic BF responses and insulin-dependence of intestinal GU are pivotal concepts in the regulation of glucose homeostasis in humans. Obesity influences both of these physiological concepts, whereas altered gastrointestinal anatomy, incretins responses and weight loss after bariatric surgery are able to reverse these obesity-induced perturbations leading to improved glucose homeostasis.Maha-suolikanavan aineenvaihdunta ihmisellä. PET-tutkimuksia lihavilla ja diabetesta sairastavilla potilailla Maha-suolikanavan alue käsittää lukuisten elinten, hormonien ja hermostollisten tekijöiden välisen vuorovaikutuksen ja se on keskeinen veren glukoositasapainoa säätelevä kokonaisuus niin paastossa kuin aterianjälkeisessä tilanteessa. Vaikka lihavuuden on osoitettu muuttavan maha-suolikanavan toimintaa altistaen heikentyneelle glukoosinsiedolle ja tyypin 2 diabetekselle, monia tämän alueen aineenvaihdunnallisia ja verenvirtaukseen liittyviä tekijöitä ei tunneta terveessä elimistössä eikä sairaustiloissa. Väitöskirjatyössäni osoitin että positroniemissiotomografia eli PET-kuvaus soveltuu haiman ja suoliston glukoosi- ja rasvahappoaineenvaihdunnan ja verenvirtauksen mittaamiseen ihmisillä kajoamattomasti. Tämän jälkeen hyödynsin PET-menetelmää erilaisissa tutkimusasetelmissa 62 lihavalla ja 40 terveellä koehenkilöllä. Lisäksi tutkimuksissa tarkasteltiin lihavuusleikkauksen vaikutusta koko kehon glukoosiaineenvaihduntaan ja haiman beetasolujen toimintaan. Tutkimuksessa todettiin että lihavilla koehenkilöillä oli suurentunut haiman rasvahappoaineenvaihdunta ja heidän haimansa olivat rasvoittuneempia kuin terveillä verrokeilla. Lihavien koehenkilöiden haiman glukoosiaineenvaihdunta ja verenvirtaus oli heikentynyt. Terveillä verrokeilla insuliini lisäsi suoliston glukoosinottokykyä lähes kolminkertaisesti paastonaikaiseen tilanteeseen verrattuna. Sen sijaan lihavilla koehenkilöillä insuliinin anto ei vaikuttanut suoliston glukoosinottokykyyn. Terveillä verrokeilla ruokailu lisäsi sekä haiman että suoliston verenvirtausta, kun taas GIP-hormonin annon aikana haiman verenvirtaus laski ja suoliston nousi. Lihavuusleikkauksen myötä haiman rasva-aineenvaihdunta ja verenvirtaus laskivat merkitsevästi. GIP-hormonin vaikutukset maha-suolikanavan verenvirtaukseen olivat samanlaisia sekä ennen leikkausta että sen jälkeen. Sen sijaan leikkauksenjälkeisessä tilanteessa ruokailun aiheuttamat maha-suolikanavan verenvirtausvasteet kiihtyivät johtuen todennäköisesti suurentuneesta mahalaukun tyhjenemisnopeudesta. Tutkimuksen perusteella maha-suolikanavan alueen elimissä tapahtuu lukuisia muutoksia lihavuuden, tyypin 2 diabeteksen ja lihavuusleikkauksen myötä. Haiman verenvirtausvasteet ja suoliston insuliinista riippuvainen glukoosinottokyky ovat merkittäviä koko kehon aineenvaihduntaa sääteleviä ilmiöitä. Vaikka lihavuus näyttää muuttavan näitä ilmiöitä, lihavuusleikkaus ja sen vaikutukset maha-suolikanavan anatomiaan, suolisto-hormonien eritykseen ja painoon kykenevät palauttamaan haitalliset muutokset johtaen parempaan glukoositasapainoon.Siirretty Doriast

The use of subclinical vascular markers of atherosclerosis in youth

The foundations for cardiovascular disease (CVD) in adults are laid in childhood and accelerated by the presence of comorbid conditions. Early detection of manifestations of cardiovascular pathology is an important clinical objective to identify those at risk for subsequent cardiovascular morbidity and events, and to initiate behavioral and medical interventions to reduce risk. Children were once considered to be at low risk, but with the growing health concerns related to lifestyle, cardiovascular screening may be needed earlier. Several noninvasive procedures are available to assess the cumulative effect of these exposures. These include carotid ultrasound, flow-mediated dilation, pulse wave velocity and measures left ventricular mass. This dissertation analyzes the comorbid conditions that increase cardiovascular risk in youth, namely obesity and low physical fitness, using carotid intima-media thickness to objectively detect early manifestations of cardiovascular pathology. Until recently researchers have not used surrogate markers of subclinical atherosclerosis to examine the role of a single bout of exercise. Utilizing the acute exercise model can be advantageous as it allows for an efficient manipulation of exercise variables and permits greater experimental control of confounding variables. It is possible that the effects of a bout of exercise can predict the effects of chronic exercise. We analyze the physiological factors pertinent to arterial stiffness using arterial distensibility and pulse wave velocity in the context of acute exercise in children and adults. In some instances, those who amend their trajectory by not maintaining risk factors into adulthood experience reductions in subclinical markers to levels associated with never having had the risk factor. Though avoidance of risk factors in youth is ideal, there is still a window for intervention where long-lasting cardiovascular effects might be avoided. In this dissertation we present preliminary findings linking modifiable youth risk factors to subclinical markers of CVD in adulthood.As bases da doença cardiovascular (DCV) em adultos são estabelecidas na infância e aceleradas pela presença de comorbidades. A deteção precoce de manifestações da patologia cardiovascular é um objetivo clínico importante na identificação daqueles com risco de subsequente morbidade e eventos cardiovasculares, e no estabelecimento de intervenções comportamentais e médicas para reduzir o risco. As crianças já foram considerados de baixo risco, mas com as crescentes preocupações de saúde associadas ao estilo de vida, o rastreio cardiovascular é cada vez mais precoce. Vários procedimentos não invasivos estão disponíveis para avaliar o efeito cumulativo dessas exposições. Estes incluem ultrassom da artéria carótida, a dilatação fluxo-mediada, velocidade de onda de pulso e medidas da massa ventricular esquerda. Esta dissertação analisa comorbidades conhecidas que aumentam o risco cardiovascular em crianças e adolescentes, como a obesidade, pressão arterial elevada e baixa aptidão física, usando a espessura da parede intima-media da carótida para detetar objetivamente as manifestações precoces de patologia cardiovascular. Até recentemente, estes marcadores subclínicos de aterosclerose foram pouco utilizados para examinar os efeitos de uma única sessão de exercício físico. No entanto, a utilização do modelo de exercício agudo pode ser vantajoso, pois permite uma manipulação eficiente das variáveis do exercício e permite maior controle experimental de variáveis de enviezamento. É possível que os efeitos de uma sessão de exercício possam prever os efeitos do exercício crónico. Nesta dissertação analisamos os fatores fisiológicos associados à rigidez arterial usando a distensibilidade arterial e velocidade da onda de pulso no contexto de exercício agudo em crianças e adultos. Em alguns casos, aqueles que melhoram o seu perfil de risco de risco para as DCV até à idade adulta experienciam reduções em marcadores subclínicos de aterosclerose para níveis saudáveis. Embora a prevenção de fatores de risco na juventude seja o ideal, existe ainda uma janela para a intervenção em que os efeitos cardiovasculares de longa duração pode ser evitada. Nesta dissertação apresentamos resultados preliminares que ligam fatores de risco modificáveis na juventude com marcadores subclínicos de DCV na idade adulta

A short endoscopic Secretin test for the diagnosis of chronic pancreatitis

Background: The diagnosis of CP is not yet clearly defined. Many national guidelines exist, but - as in many other not clearly defined diseases - there is no worldwide consensus. In CP, evaluation of exocrine pancreatic function is crucial because symptoms are often diffuse and overlooked by the doctors. Additionally, early diagnosis of exocrine pancreatic failure is important as its consequence, malnutrition and commonly abdominal pain, leads to serious complications and reduced life expectancy. Direct pancreas function testing with analyses of enzymes in duodenal juice may give this information. Aims: The main aim was to develop and establish a multimodal algorithm for the diagnoses of CP, accurate and easy to handle in clinical practice. Secondary, we wanted to simplify direct pancreas function testing including a): the performance of a short endoscopic test (article I) and b): the analyses of ingredients in duodenal juice by automation: bicarbonate (article II), Amylase (article III) and Lipase (article IV). Materials and Methods: We examined consecutively healthy controls and patients referred to our outpatient clinic due to symptoms suspicious of CP. We assessed patients with a modified Layer (Mayo) score, which includes imaging, pancreas function testing and medical history. We established a short endoscopic secretin test and analysed bicarbonate, Amylase and Lipase in duodenal juice as markers for ductal and acinar exocrine pancreatic function. In article I, we determined sensitivity, specificity and accuracy of bicarbonate and faecal-elastase, using our modified secretin-stimulated upper endoscopy (short endoscopic secretin test, or EST). In article II, III, IV, we describe correlation between automation of analyses of Bicarbonate, Amylase and Lipase in duodenal juice to labour-intensive manual methods. Results: I. Short endoscopic secretin test: Fifty-two patients aged 19 to 67 years and 25 healthy controls aged 19 to 64 years were included. Twenty-four patients fulfilled the modified Layer score for CP or non-CP. The overall accuracy of the EST versus FE1 test was 85%/71%, with positive and negative predictive values of 100%/79% and 80%/69%, respectively. II. Automation of bicarbonate measurement: 177 samples from 71 patients were analysed. Correlation coefficient of all measurements was r = 0.98 (p < 0.001). Correlation coefficient of fresh versus frozen samples conducted with automatic spectrophotometry (n = 25): r = 0.96 (p < 0.001). III. Automation of amylase measurement: We analysed 52 samples for assay of amylase in pairs. Correlation between measurements with the two methods was r = 0.99 (p < 0.001). IV. Automation of lipase measurement: We tested stability of 54 samples from 21 patients. Diluting samples with MOPS buffer, added BSA gave stable results, and was superior to diluting samples in saline. We compared the two assays in 50 samples from 20 patients and found a good correlation between the two assays (r=0.91, p < 0.001). Conclusions: I: Short EST is rapid and easy to perform and can be incorporated in daily routine in every clinical endoscopic unit. EST is superior to FE1 in the assessment of pancreatic insufficiency, leading to earlier diagnosis of moderate and early or mild CP. II: The measurement of bicarbonate in fresh and thawed samples by automatic spectrophotometric analysis correlates excellent with the back-titration gold standard. III and IV: Quantification of duodenal amylase and lipase activity with automated spectrophotometry has excellent correlation to measurements made by the manual methods. Overall, Endoscopic secretin test is easy to perform, and can be incorporated in a diagnostic endoscopic examination. Automated measurement of bicarbonate, lipase and amylase in duodenal juice simplifies the analytical methods and shortens time from test to result substantially. Standardized, centre-independent analyses of duodenal juice with quantification of ductal and acinar function in any unit with basic endoscopic and laboratory services is within reach