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The interplay of physical and molecular determinants in limb and cardiac cushion morphogenesisDamon, Brooke James, January 2007 (has links)
Thesis (Ph.D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on March 19, 2009) Vita. Includes bibliographical references.
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A comparative analysis of differences in the pelves of South African blacks and whitesPatriquin, Michelle Lyn 15 August 2005 (has links)
Correct race and sex determination of unknown skeletal material is an important aspect of forensic anthropology. Numerous studies have focused on the differences, both osteometric and morphological, between the sexes of a particular racial phenotype, between race groups, and populations. From previous work by a variety of researchers, the necessity of population specific standards for identification has been demonstrated. The purpose of this research was to examine the metric and morphological differences in the pelvis between the sexes and races of South African whites and blacks. Results will be used in developing standards of identification tailored to this population. A sample of 400 known sex/race os coxae were examined. Skeletal material was obtained from the Pretoria collection housed at the University of Pretoria, Department of Anatomy and the Dart collection located at the University of Witwatersrand, Department of Anatomical Sciences. A series of thirteen measurements and five morphological characteristics were examined. Indices were calculated from data obtained from the metric analysis. Left and right sides were examined and those bones visibly pathologically deformed were excluded from the study. Data were subjected to SPSS stepwise and direct discriminant analysis. Results showed ischial length as the most sexually dimorphic characteristic in whites, while acetabulum diameter was best in blacks. Four functions (using pelvic dimensions) were developed for determining sex. Highest accuracies were achieved from function 1 (including all dimensions) which correctly classified 92-96% of individuals. Race differences were also investigated. Pubic length was chosen as best for discriminating between races for males and iliac breadth as best in females. Accuracies were 86-89% for males and 82-88% for females. Accuracies for sex discrimination were consistent with earlier studies. Morphological results yielded >80% accuracy for all traits in white males except greater sciatic notch shape where only 33% were correctly classified. A population specific variation in sciatic notch shape was observed where >50% of the white males had a wide sciatic notch previously thought to be a female expression. Black males recorded 81 % correct classification for pubic shape and >90% for the remaining characteristics. Greater sciatic notch and pubic bone shape achieved highest accuracies with 96% for both traits in white females, and 84% and 88% in black females respectively. In conclusion, this study conclusively demonstrates that race and population differences affect the expression of sexual dimorphism and must be accounted for to develop the most effective methods of analysis. / Dissertation (MSc)--University of Pretoria, 2001. / Anatomy / unrestricted
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Studies of danshen and its constituents on rat vascular preparations. / Studies of danshen & its constituents on rat vascular preparationsJanuary 2005 (has links)
Cheung Ho Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 164-175). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.vi / Publications based on the work in this thesis --- p.vii / Table of content --- p.viii / Abbreviations --- p.xii / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Traditional Chinese Medicine --- p.1 / Chapter 1.1.1 --- Danshen --- p.2 / Chapter 1.1.2 --- Chemical constituents --- p.5 / Chapter 1.1.3 --- Pharmacological effects --- p.7 / Chapter 1.1.3.1 --- On blood vessels --- p.7 / Chapter 1.1.3.2 --- On blood pressure --- p.8 / Chapter 1.1.3.3 --- On heart --- p.8 / Chapter 1.1.3.4 --- On myocardial ischaemia and reperfusion --- p.9 / Chapter 1.1.3.5 --- On platelet activity --- p.10 / Chapter 1.1.3.6 --- Other actions --- p.11 / Chapter 1.1.4 --- Clinical studies --- p.12 / Chapter 1.2 --- The Vascular System --- p.13 / Chapter 1.2.1 --- The circulation network --- p.13 / Chapter 1.2.2 --- Physiology of blood vessels --- p.13 / Chapter 1.2.3 --- Control of vascular lone --- p.14 / Chapter 1.3 --- Mechanisms of Vasodilatation --- p.16 / Chapter 1.3.1 --- Endothelium derived relaxant factors (EDRFs) --- p.16 / Chapter 1.3.1.1 --- Nitric oxide (NO) --- p.16 / Chapter 1.3.1.2 --- Prostacyclin (PGI:) --- p.17 / Chapter 1.3.1.3 --- Endotheliun-derived hyperpolarization factors (EDHFs) --- p.18 / Chapter 1.3.1.3.1 --- Epoxyeicosatrienoic acids (EETs) --- p.19 / Chapter 1.3.1.3.2 --- Potassium ion (IC) --- p.20 / Chapter 1.3.1.3.3 --- Gap junction --- p.20 / Chapter 1.3.2 --- Signal transduction pathways --- p.21 / Chapter 1.3.2.1 --- Guanylyl cyclase-cGMP pathway --- p.21 / Chapter 1.3.2.2 --- Adenylyl cyclase-cAMP pathway --- p.22 / Chapter 1.3.3 --- Ion channels in vascular smooth muscle cell --- p.24 / Chapter 1.3.3.1 --- Potassium channels (K+ channels) --- p.24 / Chapter 1.3.3.2 --- Calcium channels (Ca2+ channels) --- p.24 / Chapter 1.3.3.3 --- Chloride channel (Cl channel) --- p.25 / Chapter 1.3.4 --- Receptor-operated mechanisms --- p.27 / Chapter 1.3.4.1 --- Muscarinic receptors --- p.27 / Chapter 1.3.4.2 --- Adrenoceptors --- p.27 / Chapter 1.3.4.3 --- Histamine receptors --- p.28 / Chapter 1.3.4.4 --- CGRP receptors --- p.29 / Chapter 1.3.4.5 --- Tachykinin receptors --- p.30 / Chapter 1.4 --- Aims of the studies --- p.31 / Chapter CHAPTER 2 --- MATERIALS AND METHODS --- p.32 / Chapter 2.1 --- Extraction of Water and Lipid-solubie Fractions from Danshen --- p.32 / Chapter 2.1.1 --- Preparation of water-soluble and lipid-soluble fractions --- p.33 / Chapter 2.2 --- Experiments on Rat Knee Joint --- p.35 / Chapter 2.2.1 --- Animals --- p.35 / Chapter 2.2.2 --- Materials --- p.35 / Chapter 2.2.3 --- Preparatory protocols --- p.37 / Chapter 2.2.3.1 --- Anaesthesia of animals --- p.37 / Chapter 2.2.3.2 --- Cannulation of trachea --- p.37 / Chapter 2.2.3.3 --- Cannulation of carotid artery --- p.38 / Chapter 2.2.3.4 --- Blood pressure measurement --- p.38 / Chapter 2.2.4 --- Measurement of knee joint blood flow --- p.39 / Chapter 2.2.4.1 --- Preparation for measurement of knee joint blood flow --- p.41 / Chapter 2.2.5 --- Experimental protocols --- p.41 / Chapter 2.2.5.1 --- Danshen on knee joint blood flow --- p.41 / Chapter 2.2.5.2 --- Antagonists on Danshen --- p.41 / Chapter 2.2.5.3 --- Positive controls --- p.43 / Chapter 2.2.6 --- Image analysis --- p.44 / Chapter 2.2.7 --- Data analysis --- p.44 / Chapter 2.3 --- Experiments on Rat Femoral Artery --- p.45 / Chapter 2.3.1 --- Animals --- p.45 / Chapter 2.3.2 --- Materials --- p.45 / Chapter 2.3.2.1 --- Chemicals --- p.45 / Chapter 2.3.2.2 --- Physiological salt solution --- p.48 / Chapter 2.3.3 --- Preparatory protocols --- p.48 / Chapter 2.3.3.1 --- Small vessel myograph --- p.48 / Chapter 2.3.3.2 --- Isolation and mounting of tissue --- p.49 / Chapter 2.3.4 --- Experimental protocols --- p.50 / Chapter 2.3.4.1 --- Studies on the vasodilator response to Danshen --- p.50 / Chapter 2.3.4.2 --- Studies of antagonists on Danshen --- p.50 / Chapter 2.3.4.2.1 --- Endothelium-dependent mechanisms --- p.51 / Chapter 2.3.4.2.2 --- Endothelium-independent mechanisms --- p.54 / Chapter 2.3.4.2.3 --- K+ channel blockers --- p.54 / Chapter 2.3.4.2.4 --- Positive controls --- p.55 / Chapter 2.3.4.3 --- Danshen on Ca2+-induced contraction --- p.56 / Chapter 2.3.5 --- Data analysis --- p.57 / Chapter CHAPTER 3 --- RESULTS --- p.58 / Chapter 3.1 --- Danshen on Rat Knee Joint Blood Flow --- p.58 / Chapter 3.1.1 --- Topical administration of Danshen --- p.58 / Chapter 3.1.2 --- Antagonists on Danshen --- p.59 / Chapter 3.1.2.1 --- Muscarinic receptor antagonist --- p.59 / Chapter 3.1.2.2 --- β-adrenoceptor antagonist --- p.60 / Chapter 3.1.2.3 --- Histamine receptor antagonists --- p.60 / Chapter 3.1.2.4 --- Nitric oxide synthase inhibitor --- p.61 / Chapter 3.1.2.5 --- Cyclo-oxygenase inhibitors --- p.62 / Chapter 3.1.2.6 --- CGRPi receptor antagonist --- p.62 / Chapter 3.1.2.7 --- NK1 receptor antagonist --- p.63 / Chapter 3.1.2.8 --- Potassium channel inhibitor --- p.64 / Chapter 3.1.2.9 --- "Combination of cyclo-oxygenase inhibitor, nitric oxide synthase inhibitor and CGRP1 receptor antagonist" --- p.64 / Chapter 3.1.3 --- Antagonists on water-soluble fraction of Danshen --- p.91 / Chapter 3.1.3.1 --- Nitric oxide synthase inhibitor --- p.91 / Chapter 3.1.3.2 --- Cyclo-oxygenase inhibitors --- p.91 / Chapter 3.1.3.3 --- CGRP1 receptor antagonist --- p.92 / Chapter 3.1.3.4 --- NK1 receptor antagonist --- p.92 / Chapter 3.1.3.5 --- Potassium channel inhibitor --- p.92 / Chapter 3.2 --- Danshen on Rat Femoral Artery --- p.99 / Chapter 3.2.1 --- Danshen on precontracted arterial ring --- p.99 / Chapter 3.2.2 --- Endothelium-dependent mechanisms --- p.106 / Chapter 3.2.3 --- Endothelium-independent mechanisms --- p.114 / Chapter 3.2.4 --- K+ channel blockers --- p.119 / Chapter 3.2.4.1 --- Effect on Danshen --- p.119 / Chapter 3.2.4.2 --- Effect on water-soluble and lipid-soluble fractions of Danshen --- p.121 / Chapter 3.2.4.3 --- Effect on Danshensu --- p.122 / Chapter 3.2.5 --- Danshen on Ca2+-induced contractions --- p.133 / Chapter CHAPTER 4 --- DISCUSSION --- p.138 / Chapter 4.1 --- In Vivo Studies of Danshen on Rat Knee Joint Blood Flow --- p.139 / Chapter 4.2 --- In Vitro Studies of Danshen on Isolated Rat Femoral Artery --- p.148 / Chapter 4.2.1 --- Comparisons of the use of different precontractors --- p.148 / Chapter 4.2.2 --- Investigations on endothelium-dependent mechanisms --- p.151 / Chapter 4.2.3 --- Investigations on endothelium-independent mechanisms --- p.152 / Chapter 4.2.4 --- Effects of K+ channel blockers --- p.154 / Chapter 4.2.5 --- Inhibition of Ca2+ influx in vascular smooth muscle --- p.157 / Chapter 4.3 --- Comparisons of Results from In Vivo and In Vitro Studies --- p.159 / Chapter 4.4 --- Future Studies --- p.161 / Chapter 4.5 --- Conclusion --- p.162 / REFERENCES --- p.164
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The function of Bre gene in embryonic interdigital tissues.January 2007 (has links)
Wong, Wan Man. / Thesis submitted in: December 2006. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 85-98). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract in Chinese --- p.iii / Acknowledgements --- p.v / Lists of Figures and Tables --- p.vi / Table of Abbreviations --- p.xi / Table of Contents --- p.xv / Chapter Chapter I --- Introduction / Chapter 1.1 --- Brain and Reproductive Organ Expressed Gene --- p.1 / Chapter 1.2 --- Programmed cell death --- p.4 / Chapter 1.3 --- Limb development in mouse --- p.8 / Chapter 1.4 --- Role of BRE in apoptosis --- p.12 / Chapter 1.5 --- Role of programmed cell death in interdigital tissue regression --- p.14 / Chapter 1.6 --- Aim of study --- p.17 / Chapter Chpater II --- Materials and methods / Chapter 2.1 --- Mice --- p.18 / Chapter 2.2 --- In-situ hybridization / Chapter 2.2.1 --- Histology --- p.18 / Chapter 2.2.2 --- Preparation of riboprobe for in-situ hybridization --- p.19 / Chapter 2.2.3 --- In-situ hybridization --- p.20 / Chapter 2.3 --- Interdigital tissue culture --- p.21 / Chapter 2.4 --- Gene interference / Chapter 2.4.1 --- Construction of Bre-siRNA --- p.22 / Chapter 2.4.2 --- siRNA transfection of cultured interdigital cells --- p.23 / Chapter 2.5 --- Semi-quantitative RT-PCR / Chapter 2.5.1 --- Sample collection of interdigital cells and explants --- p.23 / Chapter 2.5.2 --- RNA isolation and extraction --- p.24 / Chapter 2.5.3 --- Reverse-transcription and cDNA synthesis --- p.25 / Chapter 2.5.4 --- Polymerase chain reaction --- p.26 / Chapter 2.6 --- Assay of cell viability by MTT --- p.28 / Chapter 2.7 --- Comparative proteomics --- p.30 / Chapter 2.7.1 --- Collection of interdigital cells --- p.30 / Chapter 2.7.2 --- Preparation of cell lysate --- p.31 / Chapter 2.7.3 --- Assay of protein concentration in cell lysate --- p.31 / Chapter 2.7.4 --- Two-dimensional gel electrophoresis --- p.33 / Chapter 2.7.5 --- Protein identification by mass fingerprinting --- p.36 / Chapter 2.8 --- Statistical Method --- p.38 / Chapter Chapter III --- Results / Chapter 3.1 --- Spatial and temporal expression of Bre in murine embryonic hindlimbs --- p.39 / Chapter 3.2 --- Expression of Bre isoforms in interdigital tissues --- p.45 / Chapter 3.3 --- Silencing of Bre expression by siRNA in interdigital cells --- p.49 / Chapter 3.4 --- Effect on viability of Bre-silenced interdigital cells by siRNA --- p.51 / Chapter 3.5 --- Comparative proteomic profile of Bre-silenced interdigital cultured cells --- p.53 / Chapter 3.6 --- Identification of proteins that were differentially expressed by MALDI- TOF --- p.71 / Chapter 3.7 --- The mRNA levels of proteins identified that were differentially expressed --- p.74 / Chapter Chapter IV --- Discussion --- p.77 / References --- p.85 / Appendices --- p.99 / Publication --- p.108
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A metodologia LMS para modelagem matemática de cartas de referência de valores dinamométricos para avaliação de membros superiores / LMS methodology for mathematical modelling of reference cards of dynamometric values for evaluation of upper limbsTrotta, Juliano de 31 August 2016 (has links)
As Doenças Osteomusculares Relacionadas ao Trabalho (DORT) são as patologias que demandam atenção das empresas do setor industrial devido à alta incidência de absenteísmo e pela prevalência nos afastamentos previdenciários, sendo os membros superiores o segmento corporal mais atingido. A mensuração da força muscular através da dinamometria é um dos métodos para estimar a capacidade funcional de um indivíduo, porém as tabelas internacionais de valores dinamométricos que são utilizadas como parâmetros de normalidade são conflitantes com a população do setor industrial brasileiro. Neste contexto, percebe-se a necessidade de criar um padrão de normatização específico para o setor da indústria eletromecânica que auxilie a medicina ocupacional na percepção de aptidão para execução de uma atividade laboral, prevenindo o aparecimento de DORT. O objetivo deste estudo é desenvolver valores de normalidade nos exames de dinamometria palmar e escapular através do método de cartas percentílicas, que atendessem a população brasileira do setor industrial, correlacionando com as variáveis: faixa etária, sexo e lado de dominância, para servir de apoio na decisão de aptidão profissional. Para tanto, foi realizado um estudo retrospectivo, descritivo e transversal com 2902 funcionários saudáveis entre 16 e 63 anos, a partir de banco de dados de empresas do setor eletromecânico da região metropolitana de Curitiba. Os dados foram analisados a partir da estatística descritiva com medidas de posição e dispersão e cartas de referência foram elaboradas a partir do método LMS (Least Median Square), sendo L transformação “BoxCox”, M mediana e S coeficiente de variação. Os resultados mostraram que as medianas de dinamometrias palmares desta pesquisa estão abaixo dos estudos internacionais e que as curvas percentílicas formadas pelos valores das dinamometrias desta amostragem apresentam um valor progressivo com a idade. Para o gênero masculino, a metodologia permitiu a formatação de gráficos de que apontam intervalos normalidade de acordo com cada idade. Conclui-se assim, que os valores dinamométricos palmares e escapulares encontrados hoje na literatura internacional não se aplicam para a população do setor eletromecânico nacional. O método de cartas percentílicas relacionadas com a idade e gênero permitiu formatar uma modelagem matemática com gráficos de normalidade, de fácil empregabilidade, que quando relacionado ao grau de risco ergonômico do posto de trabalho auxilia o raciocínio médico quanto a aptidão para assumir uma determinada atividade laboral. Como proposta futura, sugere-se a continuidade de estudos com esta mesma metodologia para o gênero feminino e a associação de outros métodos tecnológicos sensíveis à detecção e prevenção de doenças osteoarticulares relacionadas ou não, com o trabalho, como a termografia / The Musculoskeletal Diseases related to work (WRMD) are the pathologies that require attention of companies in the industrial sector due to high incidence of absenteeism and the prevalence in through INSS, and the upper limbs the most affected body part. The measurement of muscular strength by grip strength is one of the methods to measure the functional capacity a person, but international tables dynamometric values that are used as normal parameters are conflicting with the population of the Brazilian industrial sector. In this context, we see the need to create a specific standards model for the electromechanical industry sector to assist occupational medicine to check the capability to execute a labor activity, preventing from DORT. The aim of this study is to develop normal values for palmar grip strength and scapular tests by percentile cards method that met the Brazilian population in the industrial sector, correlating to the variables: age, gender and hand dominance, to provide support in the fitness professional decision. A retrospective, descriptive cross-sectional study was made with 2902 healthy employees between 16 and 63 years from database of electromechanical companies of the Curitiba metropolitan area. The data was analyzed using descriptive statistics with position and dispersion measurements and reference cards have been elaborated from the LMS method (Least Median Square), where L is transformation "BoxCox", M is median and S is coefficient of variation. The results showed that the median grip dinamometric of this research are below international studies and that percentílicas curves formed by the values of dinamometrias this sample have a progressive value with age. This methodology for the male gender allowed the formatting charts that show normal ranges according to each age. It was concluded that the dynamometric values grip and scapular found today in the international literature are contradictory when applied to the population of the national electromechanical industry. Percentile cards method related to age and gender, it was possible to format a mathematical modeling with normal graphics, easy usage, when related to the degree of ergonomic risk of working location aids medical thinking as the ability to take a certain labor activity. As a future proposal, it is suggested to continue their studies with the same methodology for the female gender and the association of other technological methods sensitive to the detection and prevention of osteoarticular diseases related or not with work, as thermography.
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A metodologia LMS para modelagem matemática de cartas de referência de valores dinamométricos para avaliação de membros superiores / LMS methodology for mathematical modelling of reference cards of dynamometric values for evaluation of upper limbsTrotta, Juliano de 31 August 2016 (has links)
As Doenças Osteomusculares Relacionadas ao Trabalho (DORT) são as patologias que demandam atenção das empresas do setor industrial devido à alta incidência de absenteísmo e pela prevalência nos afastamentos previdenciários, sendo os membros superiores o segmento corporal mais atingido. A mensuração da força muscular através da dinamometria é um dos métodos para estimar a capacidade funcional de um indivíduo, porém as tabelas internacionais de valores dinamométricos que são utilizadas como parâmetros de normalidade são conflitantes com a população do setor industrial brasileiro. Neste contexto, percebe-se a necessidade de criar um padrão de normatização específico para o setor da indústria eletromecânica que auxilie a medicina ocupacional na percepção de aptidão para execução de uma atividade laboral, prevenindo o aparecimento de DORT. O objetivo deste estudo é desenvolver valores de normalidade nos exames de dinamometria palmar e escapular através do método de cartas percentílicas, que atendessem a população brasileira do setor industrial, correlacionando com as variáveis: faixa etária, sexo e lado de dominância, para servir de apoio na decisão de aptidão profissional. Para tanto, foi realizado um estudo retrospectivo, descritivo e transversal com 2902 funcionários saudáveis entre 16 e 63 anos, a partir de banco de dados de empresas do setor eletromecânico da região metropolitana de Curitiba. Os dados foram analisados a partir da estatística descritiva com medidas de posição e dispersão e cartas de referência foram elaboradas a partir do método LMS (Least Median Square), sendo L transformação “BoxCox”, M mediana e S coeficiente de variação. Os resultados mostraram que as medianas de dinamometrias palmares desta pesquisa estão abaixo dos estudos internacionais e que as curvas percentílicas formadas pelos valores das dinamometrias desta amostragem apresentam um valor progressivo com a idade. Para o gênero masculino, a metodologia permitiu a formatação de gráficos de que apontam intervalos normalidade de acordo com cada idade. Conclui-se assim, que os valores dinamométricos palmares e escapulares encontrados hoje na literatura internacional não se aplicam para a população do setor eletromecânico nacional. O método de cartas percentílicas relacionadas com a idade e gênero permitiu formatar uma modelagem matemática com gráficos de normalidade, de fácil empregabilidade, que quando relacionado ao grau de risco ergonômico do posto de trabalho auxilia o raciocínio médico quanto a aptidão para assumir uma determinada atividade laboral. Como proposta futura, sugere-se a continuidade de estudos com esta mesma metodologia para o gênero feminino e a associação de outros métodos tecnológicos sensíveis à detecção e prevenção de doenças osteoarticulares relacionadas ou não, com o trabalho, como a termografia / The Musculoskeletal Diseases related to work (WRMD) are the pathologies that require attention of companies in the industrial sector due to high incidence of absenteeism and the prevalence in through INSS, and the upper limbs the most affected body part. The measurement of muscular strength by grip strength is one of the methods to measure the functional capacity a person, but international tables dynamometric values that are used as normal parameters are conflicting with the population of the Brazilian industrial sector. In this context, we see the need to create a specific standards model for the electromechanical industry sector to assist occupational medicine to check the capability to execute a labor activity, preventing from DORT. The aim of this study is to develop normal values for palmar grip strength and scapular tests by percentile cards method that met the Brazilian population in the industrial sector, correlating to the variables: age, gender and hand dominance, to provide support in the fitness professional decision. A retrospective, descriptive cross-sectional study was made with 2902 healthy employees between 16 and 63 years from database of electromechanical companies of the Curitiba metropolitan area. The data was analyzed using descriptive statistics with position and dispersion measurements and reference cards have been elaborated from the LMS method (Least Median Square), where L is transformation "BoxCox", M is median and S is coefficient of variation. The results showed that the median grip dinamometric of this research are below international studies and that percentílicas curves formed by the values of dinamometrias this sample have a progressive value with age. This methodology for the male gender allowed the formatting charts that show normal ranges according to each age. It was concluded that the dynamometric values grip and scapular found today in the international literature are contradictory when applied to the population of the national electromechanical industry. Percentile cards method related to age and gender, it was possible to format a mathematical modeling with normal graphics, easy usage, when related to the degree of ergonomic risk of working location aids medical thinking as the ability to take a certain labor activity. As a future proposal, it is suggested to continue their studies with the same methodology for the female gender and the association of other technological methods sensitive to the detection and prevention of osteoarticular diseases related or not with work, as thermography.
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Peripheral Venous Retroperfusion: Implications for Critical Limb Ischemia and SalvageKemp, Arika D. 12 1900 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Peripheral arterial disease is caused by plaque buildup in the peripheral arteries. Standard treatments are available when the blockage is proximal and focal, however when distal and diffuse the same type of the treatment options are not beneficial due to the diseased locations. Restoration of blood flow and further salvaging of the limb in these patients can occur in a retrograde manner through the venous system, called retroperfusion or arteriovenous reversal. Retroperfusion has been explored over the last century, where early side to side artery to venous connections had issues with valve competency prohibiting distal flows, edema buildup, and heart failure. However, more recent clinical studies create a bypass to a foot vein to ensure distal flows, and though the results have been promising, it requires a lengthy invasive procedure. It is our belief that the concerns of both retroperfusion approaches can be overcome in a minimally invasive/catheter based approach in which the catheter is engineered to a specific resistance that avoids edema and the perfusion location allows for valves to be passable and flow to reach distally. In this approach, the pressure flow relations were characterized in the retroperfused venous system in ex-vivo canine legs to locate the optimal perfusion location followed by in-vivo validation of canines. Six canines were acutely injured for 1-3 hours by surgical ligation of the terminal aorta and both external iliac arteries. Retroperfusion was successfully performed on five of the dogs at the venous popliteal bifurcation for approximately one hour, where flow rates at peak pressures reached near half of forward flow (37±3 vs. 84±27ml/min) and from which the slope of the P/F curves displayed a retro venous vasculature resistance that was used to calculate the optimal catheter resistance. To assess differences in regional perfusion, microspheres were passed during retroperfusion and compared to baseline microspheres passed arterially prior to occlusion in which the ratio of retroperfusion and forward perfusion levels were near the ratio of reversed and forward venous flow (0.44) throughout the limb. Decreases in critical metabolites during injury trended towards normal levels post-retroperfusion. By identifying the popliteal bifurication as a perfusion site to restore blood flow in the entirety of the distal ischemic limb, showing reversal of injury, and knowing what catheter resistances to target for further chronic studies, steps towards controlled retroperfusion and thus more efficient treatment options can be made for severe PAD patients.
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