Thesis (Ph.D.) OGI School of Science & Engineering at OHSU, July 2007. / Includes bibliographical references (leaves 202-216).

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering; and, (B.S.)--Massachusetts Institute of Technology, Dept. of Mathematics, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING / Includes bibliographical references and index. / by Richard J. Tello. / B.S.

Orientadores: Fabio Husemann Menezes, João Poterio Filho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T12:22:37Z (GMT). No. of bitstreams: 1 FecuriJunior_Rubens_M.pdf: 5719185 bytes, checksum: e083a35f4647757fb28a54278b9718c6 (MD5) Previous issue date: 2006 / Resumo: Introdução- A gestação é considerada como fator de desenvolvimento de varizes nas pernas e um dos fatores supostamente responsável por isso, seria o aumento de pressão nas veias das pernas devido ao aumento do útero e compressão das veias ilíacas. Para avaliar a pressão nas veias das pernas em posição ortostática nos ambulatórios, o método considerado como padrão ouro, é a punção da veia diretamente, mas isso é inconveniente. Objetivos- O propósito desse estudo foi o de utilizar um método não invasivo para medir a pressão nas veias das pernas em posição ortostática; o estudo foi aplicado em um grupo controle, em um grupo de varicosos e em um grupo de gestantes no 3º trimestre da gestação e comparar os valores obtidos entre os grupos. Método- Foram selecionadas para o estudo, 24 mulheres gestantes (média das gestações de 29,7 semanas) que foram avaliadas e comparadas com um grupo de 20 pacientes com varizes e 20 pessoas de um grupo controle. Os três grupos foram submetidos a medida da pressão venosa nas pernas em posição ortostática por meio de um pletismógrafico a ar, usando transdutor diferencial de pressão; a medida da pressão encontrada foi comparada com o valor da pressão hidrostática calculada a partir do segundo espaço intercostal até o local de aplicação do manguito. Resultados- Não houve diferença estatística entre a pressão calculada nos três grupos. A média da pressão no grupo de gestantes foi de 63,5 mmHg ± 5,4 SD, e foi comparada com a pressão encontrada no grupo controle 66,1 mmHg ± 8,0 SD, (p=0.1851). A pressão medida no grupo de gestantes foi estatisticamente diferente da pressão medida no grupo das varicosas (71,0 mmHg ± 6,6 SD) ? p<0,0003). Conclusão- Não foi verificado no estudo atual aumento dos valores de pressão hidrostática nas veias das pernas no 3º trimestre da gestação / Abstract: Introduction- Pregnancy is a predisposing factor to the development of varicose veins of the lower legs. One of the possible explanations is the compression of the iliac veins by the enlarged uterus, leading to a raise in the venous pressure (VP) and consequently to the enlargement of the venous system at the legs. To evaluate the VP the gold standard is Ambulatory Venous Pressure measured b+y the venipuncture, but it is inappropriate. The purpose of this study is to measure the VP at the legs, in the standing position, in a control group, varicose women and in a group of women in the third trimester of pregnancy, using a new non-invasive technique. Method- Twenty-four pregnant women (mean pregnancy age 29.7 weeks) were evaluated and compared to a group of 20 patients presenting with varicose veins and a group of 20 control volunteers. The three groups were submitted to VP measurement in the standing position by means of air-plethysmography using a pressure differential transducer; the measured pressures (MP) were compared to the hydrostatic pressures calculated (CP) from the second intercostal space to the level of the leg cuff. Results- There was no statistic difference between the mean CP of the three groups. The mean MP in the pregnancy group was 63.5 mmHg ± 5.4 SD, and it was comparable to the MP of the normal volunteers, 66.1 mmHg ± 8.0 SD, (p = 0.1851). The MP of the pregnancy group was statistically different from the mean MP of the varicose veins group (71.0 mmHg ± 6.6 SD, -p<0.0003). Conclusion- There is no increase in the hydrostatic pressure in the leg veins at the end of pregnancy / Mestrado / Cirurgia / Mestre em Cirurgia

Thesis (MScMedSc)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: An important next step to Tuberculosis control relies on the translation of basic science and modern diagnostic techniques into primary health care clinics. These assays must be rapid, inexpensive, interpretation of results must be easy and they must be simple so that a healthcare worker with limited training can perform the tests under safe conditions. This study consists of four aims. The first aim was to develop a methodology to sterilize sputum specimens for rapid TB diagnosis and drug resistance testing. Candidate bactericides were identified from the literature, and tested for their bactericidal activity in Mycobacterium tuberculosis. We identified ultraseptin®aktiv as a powerful bactericidal agent which sterilizes sputum specimens for subsequent safe handling prior to light emitting diode microscopy and it also provides a DNA template for PCR-based tests. An algorithm has been proposed for the processing of specimens and rapid diagnosis of TB and drug resistant TB while patients wait for results. Recently, the World Health Organization has endorsed the MTBDRplus test for diagnosis of TB and drug resistant TB. However genotypic tests may have more problems than anticipated. With the HIV pandemic, an increase of non-tuberculous mycobacteria has been reported. The sensitivity of genotypic tests in specimens with underlying non-tuberculous mycobacterial species therefore requires further evaluation. This study therefore also aimed at determining the reliability of the MTBDRplus assay for detection of drug resistant TB where non-tuberculous bacterial load is high. Clinically relevant non-tuberculous mycobacterium DNA and DNA from a multi-drug resistant TB isolate were obtained. Ratios of the different NTM with the MDR-TB DNA were made and subjected to the MTBDRplus assay. Known mix NTM and TB infected clinical isolates and sputum sediments were also evaluated for TB and drug resistance detection on the MTBDRplus assay. Under these conditions, this study provides evidence that the MTBDRplus test cannot reliably detect TB and drug resistance TB in specimens with underlying non-tuberculous mycobacteria. Thirdly, to evaluate the sensitivity of the MTBDRplus assay for detecting drug resistance in hetero-resistant isolates, ratios were made using purified DNA from an MDR and pan-susceptible TB isolate. The MTBDRplus assay was then performed on the different ratios. We report that the MTBDRplus assay can efficiently detect wild type DNA in genes associated with resistance during the early evolution of drug resistance. However, in the later stage during treatment when both the wild type and mutants are present, the detection limit for the mutant DNA was 1:55. Due to these results, the MTBDRplus assay should still be further improved or other tests should be developed to address these limitations. And finally to combat cross amplicon contamination during the final steps of genotypic detection with the MTBDRplus assay, a proof of concept for a patentable closed tube line probe device was proposed on the 4th aim. This device can be improved to enable automated drug resistance genotyping of multiple specimens. The results of this study highlight the need for a sensitive inexpensive point of care drug resistance test that does not require intensive training. / AFRIKAANSE OPSOMMING: 'n Belangrike volgende stap om Tuberkulose te beheer is om basiese wetenskap resultate te gebruik sodat moderne diagnose tegnieke ontwikkel kan word wat in primêre gesondheidsorg klinieke toegepas kan word. Hierdie toetse moet vinnig, goedkoop, en die interpretasie van resultate moet maklik wees. Die toetse moet eenvoudig wees sodat 'n gesondheidswerker met beperkte opleiding die toetse onder veilige omstandighede kan uitvoer. Hierdie studie bestaan uit vier doelwitte, waarvan die eerste was om 'n metode te ontwikkel vir die sterilisasie van sputum monsters vir vinnige TB diagnose en die toesting van middelweerstandigheid. Kandidaat kiemdodende middels was geïdentifiseer vanaf die literatuur en die middels se kiekdodende aktiviteit was getoets op Mycobacterium tuberculosis. Ons het ultraseptin®aktiv geïdentifiseer as 'n kragtige kiemdodende middel wat bakteria in sputum monsters steriliseer vir veilige hantering voordat diagnose met 'n lig uitstralende diode mikroskopie gedoen kan word. Hierdie behandeling met ultraseptin®aktiv bied ook 'n DNA templaat vir PCR-gebaseerde toetse. 'n Algoritme is voorgestel vir die hantering van monsters en die vinnige diagnose van sensitiewe- en middel weerstandige Tuberkulose terwyl die pasiënte by die kliniek wag vir die resultate. Onlangs het die Wêreld Gesondheid Organisasie die genotipiese MTBDRplus toets vir die diagnose van Tuberkulose en middel-weerstandige Tuberkulose onderskryf. Hierdie toets word tans op groot skaal in Suid Afrika gebruik. Dit kan egter wees dat genotipiese toetse baie meer probleme kan he as wat aanvanklik verwag is. Die HIV pandemie gaan toenemend gepaard met n toename van nie-tuberkulose mycobacteria. Die sensitiwiteit van genotipiese toetse op monsters met onderliggende nie-tuberkulose mikobakteriese spesies vereis dus verdere evaluasie. Die doel van hierdie studie was ook om die betroubaarheid van die MTBDRplus-toets te bepaal vir die opsporing van middelweerstandige TB waar die nie-tuberkulose bakteriële lading hoog is. DNA van kliniese relevante nie-tuberkulose mikobakteria en multi-middelweerstige TB isolate was bekom. Verskillende verdunnigs van die spesifieke NTM DNA te same met die van MDR-TB DNA is gemaak en onderwerp aan die MTBDRplus toets. Bekende gemengde NTM- en TB geïnfekteerde kliniese isolate en sputum sedimente was ook geevalueer vir die opsporing van TB en middel weerstandigheid met die MTBDRplus toets. Hierdie studie verskaf bewyse dat die MTBDRplus toets nie betroubaar is met die diagnose van sensitiewe- en middel weerstandige Tuberkulose in monsters met onderliggende nie-tuberkulose mycobacteria nie. Verskillende verdunnings van gesuiwerde DNA van MDR en pan-sensitiewe TB isolate is gemaak om die sensitiwiteit van die MTBDRplus toets vir die opsporing van middelweerstandigheid te bepaal. Die MDRDRplus toets is gebruik met hierdie verdunnings. Resultate in hierdie studie toon dat die MTBDRplus toets effektief is met die identifisering van wilde-tipe DNA (dit beteken middel sensitief) in gene wat geassosieer word met middel weerstandigheid gedurende die vroeë ontwikkeling van weerstandigheid. Hier teenoor toon die resultate dat in die later stadium tydens behandeling, wanneer beide die wilde-tipe (sensitief) en mutante DNA (weerstandig) teenwoordig is, is die opsporingslimiet vir die mutante DNA maar 1:55. As gevolg van hierdie resultate raai ons aan dat die MTBDRplus toets nog verder verbeter moet word of dat ander toetse ontwikkel moet word om hierdie beperkinge aan te spreek. Amplikon kruiskontaminasie kan n groot impak hê op die betroubaarheid van enige genotipiese diagnostiese toets. Die finale stappe van MTBDRplus toets behels die gebruik van 'n oop sisteem sodat kontaminasie maklik kan plaasvind. In die 4de doewit 'n konsep vir 'n patenteerbare geslotebuis toestel ontwikkel en die resultate het getoon dat kontaminasie suksesvol uitgeskakel kan word. Hierdie toestel kan verbeter na 'n outomatiese apparaat verbeter word sodat die module genotipering van verskeie monsters moontlik kan maak. Die resultate van hierdie studie beklemtoon die noodsaaklikheid van 'n sensitiewe goedkoop “point of care” diagnostiese toets wat nie intensiewe opleiding benodig nie. / Medical Research Council of South Africa / University of Stellenbosch, Dept. of Molecular Biology and Human Genetics