Thesis (M.D.)--University of Hong Kong, 1972. / Also available in print.

Thesis (M.D.)--University of Hong Kong, 1987. / Also available in electronic format. Also available in print.

Thesis (Ph. D.)--University of Sydney, 2008. / Title from title screen (viewed Jan. 28, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Public Health, Faculty of Medicine. Includes bibliographical references and list of publications. Also available in print form.

Η μελέτη αυτή είναι από τις πρώτες που ασχολήθηκαν με τη διερεύνηση του ρόλου της ενδοθηλίνης στη νεφρική νόσο, καθώς και με την παραγωγή της στο νεφρικό ιστό. Στο πρώτο μέρος της διατριβής επιλέχθηκαν δύο ομάδες ασθενών στις οποίες προσδιορίστηκαν τα επίπεδα ενδοθηλίνης-1 στο πλάσμα και στα ούρα: α) ασθενείς με νεφρωσικό σύνδρομο και β) ασθενείς με ΧΝΑ, χωρίς πρωτεϊνουρία. Στη συνέχεια εξετάστηκε κατά πόσο υπήρχε συσχετισμός των επιπέδων της ΕΤ-1 με διαφορετικές νεφρικές παραμέτρους μεγέθη όπως η κάθαρση της κρεατινίνης, η πρωτεϊνουρία και η ροή των ούρων. Τα πρώτα αποτελέσματα παρείχαν ενδείξεις για αυξημένη νεφρική παραγωγή ενδοθηλίνης-1 σε ασθενείς με σπειραματική βλάβη και η απεκκρινόμενη ΕΤ-1 είχε θετική συσχέτιση με το βαθμό της πρωτεϊνουρίας. Στη συνέχεια μελετήθηκε η έκφραση της στο νεφρικό ιστό και ακόμα ειδικότερα, στο σπείραμα, στα σωληνάρια και στο διάμεσο ιστό, καθώς και η μεταβολή των επιπέδων της απεκκρινόμενης ΕΤ-1 κατά τη θεραπευτική αντιμετώπιση της πρωτεϊνουρίας. Πιο αναλυτικά τα αποτελέσματα της διατριβής ήταν τα παρακάτω: α) Τα επίπεδα ΕΤ-1 στο πλάσμα ασθενών με νεφρική νόσο είναι αυξημένα και περίπου τριπλάσια από τα φυσιολογικά. Η αύξηση αυτή είναι ανεξάρτητη από την κάθαρση της κρεατινίνης και από το βαθμό ή την ύπαρξη της πρωτεϊνουρίας. β) Η απεκκρινόμενη ΕΤ-1 στα ούρα ασθενών με νεφρική νόσο, είναι αυξημένη στο διπλάσιο σε σύγκριση με τα φυσιολογικά επίπεδα και αντικατοπτρίζει τη νεφρική της παραγωγή. γ) Η ΕΤ-1 εντοπίζεται στο κυτταρόπλασμα των ενδοθηλιακών κυττάρων του σπειράματος και στα αγγεία του διάμεσου ιστού στο φυσιολογικό νεφρικό παρέγχυμα. δ) Στο νεφρικό ιστό των νεφρωσικών ασθενών η ΕΤ-1 εκτός από το σπείραμα και τα αγγεία του διάμεσου ιστού, εντοπίζεται και στο κυτταρόπλασμα των επιθηλιακών κυττάρων των σωληναρίων (εγγύς και άπω). ε) Δεν παρατηρείται καμία διαφορά στην κατανομή της ΕΤ-1 στις διάφορες τομές μεταξύ των ασθενών με νεφρωσικό σύνδρομο. Η κατανομή της ΕΤ-1 είναι ίδια και είναι ανεξάρτητη από τις διάφορες σπειραματικές νόσους στις οποίες οφείλεται η πρωτεϊνουρία. στ) Συνοπτικά, η έκφραση της ΕΤ-1 είναι μεγαλύτερη στο νεφρικό ιστό των ασθενών με πρωτεϊνουρία σε σύγκριση με την ομάδα των τομών από φυσιολογικό νεφρικό ιστό. ζ) Η απεκκρινόμενη ΕΤ-1 στα ούρα είναι ανάλογη του βαθμού της πρωτεϊνουρίας σε ασθενείς με νεφρωσικό σύνδρομο και μειώνεται παράλληλα με την πρωτεϊνουρία μετά από θεραπευτική αγωγή. / This study investigates the role of endothelin-1 (ET-1) and its production in the renal tissue. Endothelin-1 was determined in plasma and urine in two groups of renal patients: a) patients with nephrotic syndrome and b) patients with chronic renal failure without proteinuria. Endothelin levels were correlated with several renal function parameters such as creatinin clearance, proteinuria and urinary flow. Results showed an increased endothelin renal production in patients with glomerular injury and a positive correlation between endothelin renal excretion and proteinuria. The endothelin expression in the renal tissue was studied and particularly in the glomerulus, tubules and interstitial tissue. Further more, changes in endothelin renal excretion were investigated during immunosuppressive treatment of proteinuria. The results of this study are as follow: a) Endothelin-1 plasma levels in patients with renal disease are increased compared to controls. This increase was independent compared to creatinine clearance and the severity of proteinuria. b) The endothelin renal excretion in patients with renal disease is increased compared to controls and represents its renal production. c) ΕΤ-1 is localized in the cytoplasm of glomerular endothelial cells and in the vessel walls in the interstitial tissue in normal renal parenchyma. d) In patients with neprotic syndrome, ET-1 is also localized in the cytoplasm of epithelial cells in proximal and distal tubules. e) No differences in the renal distribution of ET-1 were observed among tissue samples of nephrotic patients with different primary causes of proteinuria. f) The ΕΤ-1 expression was increased in the renal tissue of patients with proteinuria compared to controls. g) The ΕΤ-1 excretion in urine was positive correlated to the degree of proteinuria and decreases with the reduction of proteinuria after immunosuppressive treatment.

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Orientador: André Luis Balbi / Banca: Jacqueline Teixeira Caramori / Banca: Pedro Alejandro Gordan / Resumo: A Insuficiência Renal Aguda apresenta uma alta incidência em pacientes internados em hospitais terciários, principalmente em Unidades de Terapia Intensiva, estando associada a elevada mortalidade. Este trabalho tem como objetivos descrever a população de pacientes internados no Hospital das Clínicas de Faculdade de Medicina de Botucatu - UNESP com diagnóstico de Insuficiência Renal Aguda atendidos pelo Grupo de Interconsultas do Serviço de Nefrologia e avaliar os fatores de risco associados ao óbito nestes pacientes. Foram acompanhados 946 pacientes no período de abril de 2002 a dezembro de 2006, todos maiores de 12 anos, com diagnóstico de Necrose Tubular Aguda e internados nas diferentes enfermarias e Unidades de Terapia Intensiva do Hospital das Clínicas, exceto na Pediatria e Nefrologia. Insuficiência Renal Aguda foi definida como um aumento de creatinina sérica de pelo menos 30% de seu valor basal em período mínimo de 48 horas. A média de idade foi de 61,8 ± 16,7 anos, com predomínio do sexo masculino (61,9%). Pacientes provenientes de enfermarias clínicas foram mais freqüentes (62,1%), sendo que 15,9% estavam internados na cardiologia e 15,2% na clínica médica geral, enquanto 13,3% estavam internados na enfermaria de gastroenterologia cirúrgica. 46,1% estavam internados em Unidades de Terapia Intensiva e a sepse esteve presente em 9,7% dos casos. Isquemia (51,2%) foi a etiologia mais freqüente e o tempo de acompanhamento nefrológico apresentou mediana de 7,5 dias, com intervalo interquartílico de 4 a 14 dias. / Abstract: Acute Renal Failure (ARF) present a high incidence in critically ill patients taken into tertiary care hospitais, mostly in the Intensive Care Unit (ICU) patients, were also associate with great mortality rate. The objective of this work was to describe the population of patients hospitalized in the School Medicine, Botucatu- UNESP with diagnosis of ARF, attended by Group of - Interconsults of Service Nephrology and to evaluate the risk factors associate with death in this patients. This was a cohort study which evaluated 946 patients with ARF, from April 2002 to December 2006, was included patients older than 12 years, with diagnosis of ARF due to Acute Tubular Necrosis (ATN) and hospitalized in wards and ICU of HC- FMBUNESP (except in the Pediatrics and Nephroloy wards). ARF was defined as serum creatinine at least 30% above basal value from 48 hours at minimum. The average of age was 61,8 ± 16,7 years, with predominantly masculine gender (61,9%). 15,9% were hospitalized in the cardiology and 15,2% in the clinical medical, while 13,3% were hospitalized in the gastroenterology surgical ward. 46,1% of patients were hospitalized in ICU and the sepsis was present in 9,7% of the cases. Ischemia was the etiology more frequent (51,2%) and the time of accompaniment nephrologic presented an median of 7,5 days (4 - 14). / Mestre

Orientador: Luiz Antônio de Lima Resende / Banca: Luiz Antônio de Lima Resende / Banca: Pasqual Barretti / Banca: Heloisa Almeida de Lima Castro / Resumo: Este trabalho analisa alterações odontológicas em pacientes com insuficiência renal crônica, em programa de hemodiálise. As alterações odontológicas estudadas foram índice de dentes cariados, perdidos e obturados (CPOD), presença ou ausência de doença periodontal, número de desdentados totais e parciais. Os pacientes foram submetidos a exame neurológico dos nervos cranianos. Foi determinado o pH da saliva antes e após diálise. Dentre os 44 pacientes estudados, foram encontrados 23 desdentados totais, 7 desdentados parciais e 14 dentados. Vários apresentaram cáries, sem diferenças estatisticamente significativas em relação ao grupo controle; 7 pacientes apresentaram doença periodontal. Alterações de nervos cranianos foram encontradas em 36 pacientes. Os nervos cranianos mais freqüentemente acometidos foram VIII - vestíbulo-coclear, II - óptico e V - trigêmio. Alterações trigeminais foram encontradas em 20 pacientes. É provável que as alterações trigeminais aferentes estejam relacionadas com as perdas dentárias, na insuficiência renal crônica. / Abstract: This paper analyzes odontological alterations in hemodialysis patients with chronic renal failure. Odontological alterations were: index of decayed, lost, or filled teeth (DLFT); presence or absence of periodontal disease; and totally and partially toothless. Patients were submitted to neurological examination of the cranial nerves. Saliva pH was recorded before and after dialysis. Out of 44 patients, 23 were totally toothless, 7 partially toothless, and 14 dentate. Several had decay, but this was not statistically significant to controls; 7 had periodontal disease. Cranial nerve alterations were found in 36 patients. The most frequently compromised nerves were the VIII - vestibulocochlear, II - optic, and V - trigeminal. Trigeminal alterations were found in 20 patients. Probably afferent trigeminal alterations are related to tooth loss in chronic renal failure. / Mestre

In adult horses and foals, renal dysfunction can occur as a secondary complication to gastrointestinal disorders, dehydration, septicemia, endotoxemia and nephrotoxic drug administration. Measurement of renal function is an important feature not only in the diagnosis, but also in the prognosis and management of renal disease. Commonly used drugs such as phenylbutazone and gentamicin can be highly nephrotoxic under certain conditions. Estimation of the glomerular filtration rate (GFR), accepted as one of the earliest and most sensitive assessments of renal function, can be determined in horses using standard techniques such as endogenous or exogenous renal creatinine clearance. These techniques can be time consuming, dangerous to perform on fractious patients, require trained personnel and are subject to errors most often associated with improper or incomplete urine collection. Recently, tests using iohexol, a radiographic contrast agent, have been developed to estimate the GFR in human beings, pigs, sheep, dogs, cats and horse foals with results that have been validated by traditional standards. Serum clearance of a substance that is freely filtered by the kidneys without tubular secretion or reabsorption, that is not protein bound, and that is not metabolized, is a measurement of glomerular filtration rate. Iohexol meets all of these requirements and thus its clearance from serum should accurately estimate GFR. Utilization of serum clearance studies for estimation of GFR provides a clinically feasible and reproducible method in order to measure GFR in horses. Other commonly used methods to assess renal function in horses are fraught with inherent and operator error. Serum clearance of iohexol does not necessitate collection of urine and has been shown to be a safe, reproducible method using collection of timed blood samples to assess renal function in humans and animals. The objectives of this project were 1) to determine a method of estimation of GFR based on serum clearance of a substance that meets the requirements of a marker for GFR, and 2) to make the method clinically applicable by developing a method using two blood samples to derive clearance and thus GFR in normal adult horses. Results of this study showed good agreement between GFR derived by exogenous creatinine clearance and serum clearance of iohexol. In addition, GFR values for all horses using either method were within published reference ranges for this species. The results of this study indicate that a single intravenous injection of iohexol at a dose of 150 mg/kg, followed by collection of 2 serum samples at 3 and 4 hours post injection can be used to estimate the GFR in healthy horses. / Master of Science

The Severity of Renal Disease Scale (SORDS) was developed to provide a single score reflecting disease severity of renal patients independent of confounding psychosocial influences. This study examined SORDS' reliability and validity and its relevance as a research tool assessing the psychological effect of illness severity. Data was collected from 127 renal patients (predialysis, HD, CAPD). SORDS was compared with the Endstage Renal Disease Severity Index (ESRD-SI), the SF-36, the Beck Depression Inventory - 2nd Edition and a subset of BDI-II items reflecting cognitive features only at differing stages of renal disease and time on dialysis. SORDS and ESRD-SI data from twenty-two CAPD patients was included in reliability analyses. SORDS reliability estimates were low suggesting that the use of SORDS with medical chart data at this time is problematic. SORDS should be used only by medical practitioners who are aware of patients' standing on SORDS variables. There was however strong support for SORDS' validity. Validity was demonstrated by correlations between SORDS and the ESRD-SI. Compared to the ESRD-SI, SORDS was better able to discriminate between dialysis and pre-dialysis patients. SORDS and ESRD-SI scores were related to self-perceptions of decreased health status on the SF-36 independent of dialysis duration and age. SORDS utility in psychosocial research with renal patients was demonstrated by a finding that disease severity differentially impacts levels of depression for HD versus CAPD patients independent of age or dialysis duration. At the lowest level of illness severity as assessed by SORDS, CAPD patients scored in the moderate range of depression and were significantly more depressed than HD patients. Using the same analyses but with the ESRD-SI, no differences in level of depression were detected. These results imply a relationship between adjustment to treatment and illness severity. It is concluded that SORDS is a valid index of renal disease severity and that illness severity as assessed by SORDS may have an important role as a moderator variable in psychosocial research with renal patients. These results may have important implications for treatment assignment and psychosocial assessment and intervention of renal patients and their families.

People living with renal failure experience enormous challenges, yet very little is known about life with this disease. The goal of this research was to gain an integrated understanding of the lives of people with renal failure. An understanding of life with renal failure that includes cultural, institutional and historical contexts may provide health care practitioners with the kind of information and insights necessary to improve medical practice. Thus far, medical practice has been based on a biomedical model of care that focuses almost exclusively on the physical aspects of illness. From this perspective, people with kidney disease are seen as autonomous and rational individuals. In this research, a sociocultural multiple case study approach was utilized in order to gain a situated understanding of life for four people with renal disease. This research revealed that life with renal failure is work. While it is the people living with renal failure who do the bulk of the work, friends and family also work to "live" with renal disease. Participants and their significant others learn about and become experts on life with this disease. A gap was found between practitioners' understanding of disease and participants' lived experience — resulting in many negative repercussions. Medical-based knowledge is lacking because it does not consider the three relevant sources of knowledge: practitioners, participants and participants' significant others. This research argues for a bridge between the home world and the hospital world, so that a broader community of practice is created. An account of the lived experience of people with renal failure that includes these factors can inform "best practice" because it provides a richer and more authentic picture of life with this illness. It is from this perspective that health care practitioners can begin to broaden their understanding of renal failure as it is "lived", and, so informed, can better provide the kinds of education and support that will enhance the lives of people with this illness.