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Betaine analogues and related compounds for biomedical applicationsVasudevamurthy, Madhusudan January 2006 (has links)
Living cells accumulate compensatory solutes for protection against the harmful effects of extreme environmental conditions such as high salinity, temperature and desiccation. Even at high concentrations these solutes do not disrupt the normal cellular functions and at times counteract by stabilizing the cellular components. These properties of compensatory solutes have been exploited for stabilizing proteins and cells in vitro. Betaines are widespread natural compensatory solutes that have also been used in other applications such as therapeutic agents and polymerase chain reaction (PCR) enhancers. Some biomedical applications of novel synthetic analogues of natural betaines were investigated. Natural compensatory solutes are either dipolar zwitterionic compounds or polyhydroxyl compounds, and the physical basis of compensation may differ between these, so one focus was on synthetic betaines with hydroxyl substituents. The majority of the synthetic solutes stabilized different model proteins against stress factors such as high and low temperatures. The presence of hydroxyl groups improved protection against desiccation. The observed stabilization effect is not just on the catalytic activity of the enzyme, but also on its structural conformation. Synthetic compensatory solutes have a potential application as protein stabilizers. Dimethylthetin was evaluated as a therapeutic agent and found to be harmful in a sheep model. However, from the study we were able to generate a large-animal continuous ambulatory peritoneal dialysis (CAPD) model and showed that glycine betaine could be added to the dialysis fluid in chronic renal failure. Some synthetic compensatory solutes reduce the melting temperatures of DNA better than most natural solutes. Synthetic solutes were identified that have potential to enhance PCR and could replace some reagents marketed by commercial suppliers. Density, viscosity and molecular model data on the solutes showed correlations with the biochemical effects of the solutes, but no physical measurements were found that reliably predicted their potential for biotechnological applications.
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Χαρακτηριστικά του τρόπου ζωής των ασθενών με χρόνια νεφρική ανεπάρκεια που υποβάλλονται σε θεραπεία υποκατάστασης της νεφρικής λειτουργίας με αιμοκάθαρση, περιτοναϊκή κάθαρση, ή έχουν υποβληθεί σε επιτυχή μεταμόσχευση νεφρούΠαναγοπούλου, Αλκυόνη 07 June 2010 (has links)
Η εργασία αυτή αποτελεί μία από τις πρώτες που ασχολήθηκαν με τη διερεύνηση του τρόπου ζωής των ασθενών με χρόνια νεφρική ανεπάρκεια τελικού σταδίου, οι οποίοι υποβάλλονται σε μέθοδο υποκατάστασης της νεφρικής λειτουργίας με αιμοκάθαρση ή περιτοναϊκή κάθαρση ή έχουν υποβληθεί σε επιτυχή μεταμόσχευση νεφρού στον Ελλαδικό χώρο και συγκρίνει τα αποτελέσματα με τα υπάρχοντα από ανάλογες εργασίες που έχουν επιτελεστεί στην Ευρώπη και στη Βόρειο Αμερική.
Στο πρώτο μέρος της διατριβής έγινε αναφορά: α) στους νεφρούς και στη λειτουργία τους και β) στη διαχρονική εξέλιξη των μεθόδων υποκατάστασης της νεφρικής λειτουργίας.
Στο δεύτερο μέρος αναφέρθηκαν τα γενικά χαρακτηριστικά των ασθενών σε υποκατάσταση και στη συνέχεια τα ιδιαίτερα χαρακτηριστικά ανάλογα με την μέθοδο υποκατάστασης της νεφρικής λειτουργίας, αιμοκάθαρση ,περιτοναϊκή κάθαρση ή μεταμόσχευση
Στη συνέχεια για κάθε ομάδα ασθενών προσδιορίστηκαν:
α) δημογραφικά χαρακτηριστικά (ηλικία, οικογενειακή κατάσταση, τόπος κατοικίας, γραμματικές γνώσεις, χρονικό διάστημα σε υποκατάσταση)
β) επαγγελματική κατάσταση
γ) δραστηριότητες και φυσική κατάσταση
δ) κοινωνική κατάσταση (σεξουαλική ζωή, συμμετοχή στις κοινωνικές εκδηλώσεις, ικανοποίηση από τη ζωή, τις κοινωνικές παροχές, την ιατρική και νοσηλευτική φροντίδα, σχέσεις με οικογενειακό και φιλικό περιβάλλον )
ε) ψυχολογική κατάσταση ως προς το άγχος και την κατάθλιψη και
ζ) έγινε σύγκριση των αποτελεσμάτων με αυτά από ανάλογες εργασίες που έχουν επιτελεστεί στον Ευρωπαϊκό και στον βόρειο-αμερικανικό χώρο.
Από τα αποτελέσματα της διατριβής προκύπτει ότι από τις διάφορες μεθόδους αντιμετώπισης της ΧΝΝ τελικού σταδίου, η νεφρική μεταμόσχευση φαίνεται να υπερέχει, συμβάλλοντας σε καλύτερο βαθμό συνολικής αποκατάστασης, αφού εξασφαλίζει βελτιωμένη φυσική κατάσταση, καλύτερη επαγγελματική αποκατάσταση και κοινωνική ευεξία.
Ακολουθούν οι ασθενείς υπό ΣΦΠΚ οι οποίοι φαίνεται να έχουν καλύτερη ψυχολογική προσαρμογή με λιγότερο stress, άγχος και κατάθλιψη, μεγαλύτερη αυτονομία και ανεξαρτησία. Αυτό τους διευκολύνει για καλύτερη κοινωνική προσαρμογή με μεγαλύτερες δυνατότητες και ευκαιρίες απασχόλησης και κοινωνικής δραστηριοποίησης.
Αντίστοιχα η ζωή των ασθενών υπό ΑΚ επηρεάζεται ιδιαίτερα, ο τρόπος ζωής αλλάζει δραματικά σε όλους τους παραπάνω τομείς, αν και δείχνουν να προσαρμόζονται καλύτερα στις αντίξοες συνθήκες που βιώνουν έναντι των ασθενών άλλων χωρών.
Πιο αναλυτικά τα αποτελέσματα της διατριβής ήταν τα παρακάτω:
- Οι ασθενείς των ομάδων ΑΚ και ΣΦΠΚ είναι κυρίως ηλικιωμένα άτομα, ενώ οι μεταμοσχευμένοι ασθενείς είναι άτομα νεαρής ηλικίας. Ως προς την οικογενειακή κατάσταση και τον τόπο κατοικίας και οι τρεις ομάδες ακολουθούν την κατανομή του γενικού πληθυσμού. Οι γραμματικές γνώσεις των ασθενών των ομάδων ΑΚ και ΣΦΠΚ είναι κυρίως επιπέδου δημοτικού σχολείου, ενώ των μεταμοσχευμένων ασθενών επιπέδου γυμνασίου. Μεγαλύτερο χρονικό διάστημα σε θεραπεία υποκατάστασης παρουσιάζουν οι μεταμοσχευμένοι ασθενείς.
- Οι μεταμοσχευμένοι ασθενείς παρουσιάζουν καλύτερη επαγγελματική αποκατάσταση και ακολουθούν οι ασθενείς υπό ΣΦΠΚ, ενώ το ποσοστό των ασθενών υπό Α/Κ που εργάζεται είναι πολύ μικρό.
- Προβάδισμα στις δραστηριότητες, φυσική κατάσταση έχουν και πάλι οι μεταμοσχευμένοι ασθενείς έναντι των άλλων ομάδων και ακολουθούν οι ασθενείς υπό ΣΦΠΚ.
- Οι μεταμοσχευμένοι ασθενείς παρουσιάζουν καλύτερο επίπεδο κοινωνικής κατάστασης.
- Σε καλύτερη ψυχολογική κατάσταση βρίσκονται οι ασθενείς υπό ΣΦΠΚ και ακολουθούν με μικρή διαφορά οι μεταμοσχευμένοι.
- Αντίστοιχα αποτελέσματα δίνουν έρευνες που έχουν γίνει σε ασθενείς σε άλλες Ευρωπαϊκές και Βόρειο-Αμερικανικές χώρες αν και οι ασθενείς της παρούσας έρευνας και των τριών ομάδων δείχνουν να έχουν καλύτερους δείκτες αναφορικά με τις παραπάνω παραμέτρους και να προσαρμόζονται καλύτερα στις αντίξοες συνθήκες που βιώνουν, έναντι των ασθενών άλλων χωρών. / The present work is one of the first dealing with the study of the lifestyle of patients with end stage renal failure, under renal function substitution with haemodialysis or peritoneal dialysis or successful kidney transplantation, in Greece, and compares this data with existing results from Europe and North America.
In the first part of the thesis there is a presentation of: a) the kidneys and their function and b) the evolution of renal function substitution methods through time.
In the second part, the general characteristics of the included patients are reported, followed by the specific characteristics due to the renal substitution methods, haemodialysis, peritoneal dialysis or transplantation.
In every group of patients the following parameters were determined:
α) demographic data (age, family status, place of living, education, time in renal substitution)
β) job status
γ) activities and physical status
δ) social status (sex life, participation in social events, satisfaction due to life, social benefits, medical and nursery care, relations with friends and relatives)
ε) psychology due to stress and depression
ζ) comparison of these results with other from Europe and North America.
The results of this work reveal that renal transplantation preponderates all other substitution methods for renal function, since it guarantees improved physical status, better job rehabilitation and social welfare.
Patients in peritoneal dialysis come next in adaptation, with lesser stress anxiety and depression, bigger autonomy and independence. They have more possibilities and opportunities to work and participate in social activities.
On the contrary, the lifestyle of renal patients under dialysis is more negatively affected and their lives changes dramatically in all of the above sections; even though they seem to adapt better in the adverse conditions they are dealing with.
In detail, the results of this work are:
- Patients under haemodialysis (HD) or peritoneal dialysis (PD) are older people, while transplanted patients are younger. All patients follow the general population distribution, as for family status and place of living. The education level of the HD and PD patients is mostly elementary, while, most transplanted patients have a high school degree. These patients have spent longer periods under renal substitution.
- Transplanted patients present better job rehabilitation, followed by patients in PD, while the percentage of working patients in HD is too small.
- Transplanted patients have a better physical condition, followed by PD patents.
- Transplanted patients are in a better level of social status compared with other renal patients.
- Patients in PD seem to have a better psychological profile slightly higher than transplanted patients.
- Similar results are presented in other studies from Europe and North America, although patients of all groups, in the present work, show better indices as for the above parameters and adapt better in adverse living conditions, compared with patients of other countries.
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L’inhibition des cytochromes P450 dans les cas d’insuffisance rénale chronique : rôle de l’hormone parathyroïdienneMichaud, Josée 07 1900 (has links)
No description available.
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Avaliação da assistência e da qualidade de vida do paciente de hemodiálise na região metropolitana do Rio de Janeiro / Evaluation of care and quality of life of hemodialysis patients in the metropolitan region of Rio de JaneiroErmida, Valdir Sergio January 2009 (has links)
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Previous issue date: 2009 / Caracterizar os pacientes em hemodiálise assistidos pelo SUS na região metropolita do estado do Rio de Janeiro e avaliar a atenção a eles provida.
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Rosiglitazona, agonista do PPAR-y \"Peroxisome Proliferator-Activated Receptor-y\" reverte a nefrotoxicidade induzida pelo tenofovir-DF / The peroxisome proliferator-activated receptor-y agonist rosiglitazone reverses tenofovir-induced nephrotoxicityAlexandre Braga Libório 10 July 2008 (has links)
Introdução: A nefrotoxicidade dos antiretrovirais constituem atualmente fator importante na morbidade e mortalidade de pacientes com HIV. O tenofovir DF (TDF) se enquadra em um dos antiretrovirais mais lesivos ao rim. Conhecer seu mecanismo de nefrotoxicidade e estudar medidas protetoras podem melhorar seu uso clínico. Material e Métodos: Ratos foram tratados durante 30 dias com uma de duas doses de TDF (50 ou 300mg/Kg de dieta), sendo que um grupo teve adicionado em sua dieta maleato de rosiglitazona (RSG) na dose de 92mg/Kg de dieta nos últimos 15 dias. Após esse período, os ratos foram colocados em gaiola metabólica e sacrificados. Foram estudados parâmetros bioquímicos, fluxo sanguíneo renal e os rins extraídos para expressão semiquantitativa dos transportadores epiteliais tubulares. Resultados: Os animais que receberam TDF em dose alta apresentaram insuficiência renal severa acompanhada de redução da expressão da oxido-nítrico sintase endotelial e vasoconstricção renal intensa. Todos esses parâmetros foram parcialmente revertidos pela administração de RSG. Baixas doses de TDF não causou alteração significativa do ritmo de filtração glomerular, porém induziu fosfatúria, acidose tubular proximal, poliúria e redução da capacidade de concentração urinária. Essas alterações foram associadas a redução da expressão de alguns transportadores epiteliais (cotransportador sódio-fosforo, contratransportador sódio-hidrogênio tipo 3 e aquaporina tipo 2). Não foi caracterizado síndrome de Fanconi, pois não houve proteinúria ou glicosúria. O tratamento com RSG reverteu todos os parâmetros de nefrotoxicidade estudados, normalizando as alterações bioquímicas urinárias e a expressão dos transportadores de membrana. Conclusões: Os achados desses experimentos tem potencial aplicação clínica em pacientes com nefrotoxicidade induzida pelo TDF, especialmente naqueles com hipofosfatemia e/ou redução do ritmo de filtração glomerular. / Objective: To characterize the mechanisms of tenofovir disoproxil fumarate (TDF)- induced nephrotoxicity and the protective effects of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-y agonist. Methods: Rats were treated for 30 days with one of two TDF doses (50 or 300 mg/kg of food), to which RSG (92 mg/kg of food) was added for the last 15 days. Biochemical parameters were measured, and renal tissue was extracted for immunoblotting. Results: Mean daily ingestion was comparable among all the treated groups. Highdose TDF induced severe renal failure accompanied by reduced expression of endothelial nitric-oxide synthase and intense renal vasoconstriction. All of these features were ameliorated by RSG administration. Low-dose TDF did not alter the glomerular filtration rate but induced significant phosphaturia, proximal tubular acidosis and polyuria, as well as reducing urinary concentrating ability. These alterations were caused by specific downregulation of the sodium-phosphorus cotransporter, sodium/hydrogen exchanger 3 and aquaporin 2. No Fanconi\'s syndrome was identified (proteinuria was normal and there was no glycosuria). Treatment with RSG reversed TDF-induced tubular nephrotoxicity, normalizing urinary biochemical parameters and membrane transporter protein expression. Conclusion: These findings have potential clinical applications in patients presenting with TFV-induced nephrotoxicity, especially in those presenting with hypophosphatemia or a reduction in glomerular filtration rate.
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Uma proposta de intervenção ao cuidador principal dos pacientes com doença renal crônica em hemodiáliseCavalcante, Tarciana Elias 02 May 2012 (has links)
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Previous issue date: 2012-05-02 / The present study had the aim to understand repercussions of chronic renal patient s illness and hemodialysis treatment in the lives of main caregivers, with the goal to elaborate and implement a psychological-educational intervention. A qualitative research was conducted using Thematic Content Analysis technique. This study is composed by three papers: one theoretical approach and two empirical ones. In order to carry out the second and third studies, ten relatives of people with chronic renal disease in hemodialysis treatment were recruited. The first paper refers to a literature review on Chronic Renal Failure, with focus on its concept, main causes, characteristics, treatment and the history of hemodialysis. Consulted literature highlights that despite the technological evolution of hemodialysis treatment, which brought up better quality of life to chronic renal patients, it also brought up physical, emotional, social, economic and cultural implications to them and their families. The second paper is on caring and its repercussions in the family, especially regarding the main caregiver. Data analysis of the interviews showed that chronic renal disease and hemodialysis treatment require the family to adapt to a new routine and that caregivers also need caring. In the third paper, the elaboration and implementation of an intervention proposal for this group of relatives is described. Lipp's Inventory of Stress Symptoms in Adults was used to assess the level of stress in caregivers before and after the intervention. The need for relatives of patients in hemodialysis treatment to be assisted in a space that can facilitate the creation, reinvention and/or strengthening of coping mechanisms was observed. / O presente estudo teve como objetivo compreender as repercussões da doença renal crônica e do tratamento de hemodiálise na vida dos cuidadores principais, com o intuito de elaborar e implementar uma intervenção psicoeducativa. Foi realizada uma pesquisa de campo de caráter qualitativo, em que se utilizou como técnica a Análise de Conteúdo Temática. Este trabalho compreende três artigos: um teórico e dois empíricos. Para o segundo e o terceiro artigo, participaram dez cuidadores familiares dos doentes renais crônicos. O primeiro artigo fez uma revisão de literatura sobre o cenário da doença renal crônica, enfatizando conceitos, características, causas, tratamentos e a trajetória histórica da hemodiálise. A literatura consultada ressalta que apesar de o tratamento de hemodiálise ter evoluído tecnologicamente ao longo da história, trazendo uma melhor qualidade de vida aos pacientes renais crônicos, também trouxe implicações físicas, emocionais, sociais, econômicas e culturais para o paciente e para a sua família. O segundo artigo fez uma explanação acerca do cuidado e de suas ressonâncias na família, mais especificamente, no cuidador principal. A avaliação do material obtido através das entrevistas mostram que a doença renal crônica e o tratamento de hemodiálise requerem adaptações da família a uma nova rotina e que os que cuidam também necessitam ser cuidados. No terceiro artigo, descreve-se a elaboração e implementação de uma proposta de intervenção em grupo com estes familiares. Para avaliar o nível de estresse dos cuidadores, antes e após a intervenção, aplicou-se o Inventário de Sintomas de Stress para Adultos de Lipp. Foi observado o quanto se faz necessário que a família do paciente em hemodiálise também tenha um espaço que a possibilite criar, recriar e/ou fortalecer mecanismos de enfrentamento.
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Hydrodynamic delivery for the study, treatment and prevention of acute kidney injuryCorridon, Peter R. 07 July 2014 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Advancements in human genomics have simultaneously enhanced our basic understanding of the human body and ability to combat debilitating diseases. Historically, research has shown that there have been many hindrances to realizing this medicinal revolution. One hindrance, with particular regard to the kidney, has been our inability to effectively and routinely delivery genes to various loci, without inducing significant injury. However, we have recently developed a method using hydrodynamic fluid delivery that has shown substantial promise in addressing aforesaid issues. We optimized our approach and designed a method that utilizes retrograde renal vein injections to facilitate widespread and persistent plasmid and adenoviral based transgene expression in rat kidneys. Exogenous gene expression extended throughout the cortex and medulla, lasting over 1 month within comparable expression profiles, in various renal cell types without considerably impacting normal organ function. As a proof of its utility we by attempted to prevent ischemic acute kidney injury (AKI), which is a leading cause of morbidity and mortality across among global populations, by altering the mitochondrial proteome. Specifically, our hydrodynamic delivery process facilitated an upregulated expression of mitochondrial enzymes that have been suggested to provide mediation from renal ischemic injury. Remarkably, this protein upregulation significantly enhanced mitochondrial membrane potential activity, comparable to that observed from ischemic preconditioning, and provided protection against moderate ischemia-reperfusion injury, based on serum creatinine and histology analyses. Strikingly, we also determined that hydrodynamic delivery of isotonic fluid alone, given as long as 24 hours after AKI is induced, is similarly capable of blunting the extent of injury. Altogether, these results indicate the development of novel and exciting platform for the future study and management of renal injury.
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BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASEIssa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
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BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASEIssa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
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BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASEIssa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
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