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Renal hypoperfusion from renal artery stenosis (RAS) activates the renin-angiotensin system, which in turn causes volume overload and hypertension. Atherosclerosis and fibromuscular dysplasia are the most common causes of renal artery stenosis. Recurrent flash pulmonary edema, also known as Pickering syndrome, is commonly associated with bilateral renal artery stenosis. There should be a high index of clinical suspicion for renal artery stenosis in the setting of recurrent flash pulmonary edema and severe hypertension in patients with atherosclerotic disease. Duplex ultrasonography is commonly recommended as the best initial test for the detection of renal artery stenosis. Computed tomography (CT) angiography (CTA) or magnetic resonance (MR) angiography (MRA) are useful diagnostic imaging studies for the detection of renal artery stenosis in patients where duplex ultrasonography is difficult. If duplex ultrasound, CTA, and MRA are indeterminate or pose a risk of significant renal impairment, renal angiography is useful for a definitive diagnosis of RAS. The focus of medical management for RAS relies on controlling renovascular hypertension and aggressive lifestyle modification with control of atherosclerotic disease risk factors. The restoration of renal artery patency by revascularization in the setting of RAS due to atherosclerosis may help in the management of hypertension and minimize renal dysfunction.

Erythromelalgia is a neurovascular disorder which causes pain, swelling, erythema, and warmth of the distal extremities. Primary disease is due to a genetic mutation in the gene, but secondary erythromelalgia can be the consequence of a variety of underlying etiologies, including drug and toxin exposures. The disease is rare, occurring in only 1.3 out of every 100,000 in the United States, and symptoms can vary significantly in severity and presentation. Therefore, it can be difficult to recognize the disorder, identify the source, and promptly treat the condition. We report a reversible cause of erythromelalgia induced by the use of oral cyclosporine. This correlation is poorly documented in literature, with limited accounts identifying an association between erythromelalgia and cyclosporine. As drug-induced erythromelalgia represents a reversible cause of disease, physicians should obtain a detailed medication history during the diagnostic workup, specifically inquiring about the use of cyclosporine.

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While machine perfusion of explanted kidneys is theoretically superior to standard cold storage, it may damage potential transplants unless machine-associated swelling is controlled. This thesis presents the effects of perfusate tonicity on renal swelling during hypothermic machine perfusion. Phosphate buffered solution (PBS) and PBS supplemented with 5% w/v mannitol were used as isotonic (289 mOsm/kg) and hypertonic (568 mOsm/kg) perfusates, respectively. Porcine kidney pairs were procured then flushed and machine perfused; the right and left kidneys were assigned opposite perfusates. An experimental methodology was developed to image porcine kidneys undergoing hypothermic machine perfusion (5 deg C) for 15 minutes followed by 120 minutes without perfusion to quantify surface displacement (renal swelling) with digital image correlation (DIC). Surface displacement and size (thickness) were compared between the right and left kidneys of each pair. In addition, discharged renal fluids (i.e., filtrate and venous outflow) and biopsies were collected. On average, kidneys perfused with the mannitol solution were smaller in size than the kidneys perfused with PBS (p < 0.05) at the start and end of each experiment; however, there was no significant difference between the renal sizes at the end of the 15 minute perfusion interval (p > 0.05). Thus, hypertonic and isotonic perfusates yielded different renal swelling outcomes (i.e., physical size and surface displacement), which suggests that perfusate tonicity influences renal swelling. These experiments are the first time ex vivo renal surface displacement measurements have been collected during machine perfusion. / Master of Science

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25189号 / 医博第5075号 / 京都大学大学院医学研究科医学専攻 / (主査)教授 平井 豊博, 教授 江木 盛時, 教授 後藤 慎平 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

It is known that there are many cardiovascular diseases caused by the alterations in the blood vessels, that affect most of the world population. The knowledge of the mechanobiological behavior of blood vessels is used for understanding how cardiovascular diseases could affect the human body. So, by studying the growth and remodeling (G&amp;R) of the arterial tree, it is possible to predict how these diseases will develop and consequently, how they can be treated or even prevented. The human body naturally tries to find the optimum steady-state by changing either the production of the constituents of the arteries or the flow rate through blood vessels. This effect is the phenomenon that is going to be studied in this thesis and these three main factors have to be taken into account when reproducing the diseases’ effects: the so-called transmural pressure, the blood flow rate, and the biomechanics of the constituents which form the arterial wall. Therefore, through numerical simulations the variation of these factors can be predicted, although always with a reliability supported by experimental data. / Se sabe que hay muchas enfermedades cardiovasculares causadas por alteraciones en los vasos sanguíneos que afectan gran parte de la población mundial. El conocimiento del comportamiento mecanobiológico de los vasos sanguíneos se usa para entender cómo estas enfermedades puede afectar al cuerpo humano. Así, estudiando el crecimiento y desarrollo (G&amp;R) del árbol arterial, es posible predecir cómo estas enfermedades se van a desarrollar y consecuentemente, cómo pueden tratarse o incluso prevenirse. El cuerpo humano tiende a buscar un estado de equilibrio óptimo de forma natural cambiando o bien la producción de los constituyentes de las arterias o bien el flujo de sangre que atraviesa los vasos sanguíneos. Este efecto es el fenómeno que va a ser estudiado en esta tesis y se ha de tener en cuenta tres factores principales cuando se quiere reproducir los efectos de dichas enfermedades: la presión transmural, el flujo de sangre y la biomecánica de los constituyentes que forman la pared arterial. Luego, a través de simulaciones numéricas la variación de estos factores puede ser predicha, aunque siempre con una veracidad aportada por datos experimentales. / Vascular occlusion, modelling, arteries, arterial tree, growth and remodelling, Murray, cerebrocardiovascular diseases, adaptation, thrombosis, calcification, anemia, polycythemia, isquemia, edema

Após um trauma cirúrgico o paciente apresenta uma resposta inflamatória que acarreta em dor, edema, calor, rubor e perda de função. Tais sintomas podem tornar o pós-operatório desagradável e diminuir a qualidade de vida. Diversos estudos utilizando terapia de fotobiomodulação com variados protocolos têm mostrado resultados favoráveis no controle do edema, limitação de abertura de boca e dor no período pós-operatório. O uso do gelo no período pós-operatório tem sido orientação e recomendação de rotina para os pacientes, porém estudos clínicos controlados mostram resultados controversos em relação aos seus reais efeitos. Neste contexto, foi realizado um ensaio clínico randomizado cruzado triplo-cego para avaliar a limitação de abertura bucal, os níveis de edema e dor no período pós-operatório da exodontia de terceiros molares inferiores após a aplicação de bolsas de gelo (controlada, assistida e padronizada) associada (LG) ou não (LPG) a sessão única de fotobiomodulação (FBM). A irradiação foi aplicada por Diodo de Arseneto de Gálio e Alumínio (AsGaAl) seguindo os parâmetros: comprimento de onda de 808 nm (infravermelho) potência de 100 mW, densidade de potência de 3.57 W. cm², área do ponto de aplicação de 0.028 cm2, densidade de energia de 107 J/cm2, energia de 3 J, duração de 30 segundos em cada ponto de aplicação, em 4 pontos equidistantes sobre a pele entre a inserção e a origem do músculo masseter no lado onde o dente foi extraído totalizando 12 J. No grupo LPG a intervenção da FBM foi placebo realizada com o equipamento desativado. A amostra final foi composta por 21 pacientes, os resultados mostraram redução significativa para o grupo LG do edema no período entre 0-24 horas para a medida Ag-Cl (p= 0.009), entre 0-7 dias para a medida Tr-Cl (p= 0.002) e redução significativa da dor no período de 48 horas (p=0.03). Não houve diferença estatisticamente significativa entre os grupos LG e LPG para a limitação de abertura bucal. Concluímos que a fotobiomodulação extraoral pelo laser de baixa potência infravermelho de Diodo de Arseneto de Gálio e Alumínio (AsGaAl), aplicada em sessão única imediatamente após exodontia de terceiros molares inferiores foi capaz de melhorar os efeitos terapêuticos da aplicação local de bolsas de gelo em alguns parâmetros de edema e de dor mas não influenciou na limitação de abertura bucal. / After surgical trauma patients present inflammatory response that leads to pain, edema, heat, redness and loss of function. Such symptoms can make the postoperative unpleasant and quality of life decrease. Several studies using low power photobiomodulation therapy, with several protocols, have been performed with favorable results in the control of edema, limitation of mouth opening and pain in the postoperative period. The use of ice packs in the postoperative period has been a routine guidance and recommendation for patients, but controlled clinical trials show controversial results related to their actual effects. In this context, we conducted a randomized crossover clinical trial triple-blind to evaluate limitation of mouth opening, levels of swelling and pain in the postoperative period of third molar extraction after applying cold packs (controlled, assisted and standardized) associated with (LI) or not (LPI) to a single session of photobiomodulation therapy (PBMT). The irradiation was applied with a diode aluminum gallium arsenide laser (AlGaAs) following the parameters: wavelength of 808 nm (infrared), power of 100 mW, power density of 3.57 W. cm², application point area of 0.028 cm2, energy density of 107 J / cm2, energy of 3 J, duration of 30 seconds each application point, at 4 equidistant points on the skin between the insertion and origin of the masseter muscle on the side where the tooth was extracted, totaling 12 J. In the group LPI the PBMT intervention was placebo performed with the equipment turned off. The final sample consisted of 21 patients, the results showed a significant reduction for the LI group of edema in the period between 0-24 hours for the Ag-Cl measure (p = 0.009), between 0-7 days for the Tr-Cl measurement (p = 0.002) and significant pain reduction in the 48-hour period (p = 0.03). There was no statistically significant difference between LG and LPG groups for mouth opening limitation. We concluded that a single session of extraoral PBMT with infrared AlGaAs, applied immediately after inferior third molar extraction was able to improve effects of local application of ice packs on postoperative outcomes of edema and pain but not on mouth opening.

INTRODUÇÃO: O edema macular difuso é uma importante causa de baixa visual em portadores de diabetes mellitus. O tratamento clássico deste tipo de retinopatia consiste na fotocoagulação, entretanto, esta terapêutica é ineficaz em muitos casos. Neste trabalho, avaliou-se a eficácia do uso intravítreo da triancinolona acetonida associada à fotocoagulação com laser de argônio no tratamento do edema macular difuso diabético. Esta associação terapêutica foi comparada com o uso isolado de cada tratamento. MÉTODOS: Neste estudo, realizado entre junho de 2005 e setembro de 2006, foram estudados 30 pacientes diabéticos clinicamente controlados e portadores de edema macular difuso. Estes pacientes foram alocados de forma aleatória e proporcional em um dos seguintes grupos de tratamento: (1) fotocoagulação macular em grade com laser de argônio; (2) aplicação intravítrea de 4 mg de triancinolona acetonida; (3) associação dos itens anteriores. O seguimento foi realizado em intervalos pré-determinados de um dia, uma semana e mensalmente, até completar 6 meses. Foram analisados os parâmetros: acuidade visual corrigida LogMAR; espessura macular central e volume macular total medido pela tomografia de coerência óptica; e pressão intra-ocular aferida pelo tonômetro de Goldmann. RESULTADOS: A fotocoagulação com laser não reduziu de forma estatisticamente significativa a espessura macular central (p=0,0862) e o volume macular total (p=0,11). Esta redução foi significativa e estatisticamente semelhante nos outros dois grupos (p<0,001). Todos os grupos apresentaram melhora da acuidade visual (p=0,003), entretanto, o grupo que recebeu a associação do laser com a triancinolona intravítrea, obteve maior percentagem de pacientes com ganho de 10 ou mais letras de visão no quarto e quinto mês de seguimento (p=0,026; p=0,034). A pressão intra-ocular elevou-se em 5 mmHg ou mais em 12 pacientes, sendo seis no grupo submetido apenas a triancinolona e os outros seis no grupo que recebeu a associação de tratamento (p<0,001).Todos estes casos foram bem controlados com colírio de maleato de timolol 0,5%. CONCLUSÕES: O uso simultâneo da fotocoagulação com a triancinolona intravítrea proporcionou maior ganho de linhas de visão do que o uso isolado de cada tratamento. A fotocoagulação com laser foi a única terapia que não reduziu de forma significativa a espessura e o volume macular total e, também, foi a única que não apresentou casos de hipertensão ocular durante o seguimento. / INTRODUCTION: The diffuse macular edema is an important cause of visual impairment in diabetic subjects. Laser photocoagulation is the main treatment for this disorder, however, it is not effective in a large number of patients. In this study, we evaluated the efficacy of intravitreal use of triamcinolone acetonide combined with laser photocoagulation for the treatment of diffuse diabetic macular edema and we compare it with either laser alone or intra-vitreal triancinolone. METHODS: In this study, performed between june 2005 and september 2006, we studied 30 well controlled diabetic patients with diffuse macular edema. These patients were randomly divided into the following treatment groups: (1) macular grid photocoagulation; (2) intravitreal injection of 4 mg of triamcinolone acetonide; (3) combination of the two previous therapies. Follow up was scheduled at predetermined intervals of one day, one week and monthly until completion of six months. The following parameters were analyzed: LogMAR best corrected visual acuity; central macular thickness and total macular volume measured by ocular coherence tomography; and intraocular pressure assessed by Goldman\'s tonometer. RESULTS: Grid photocoagulation did not significantly reduce the central macular thickness (p=0,0862) or the total macular volume (p=0,11). On the other side, this reduction was significant and statistically similar in the others two groups (p<0,001). All groups improved the mean visual acuity (p=0,003), however, the group that received the association treatment had a higher percentage of patients gaining 10 or more letters at the fourth and fifth month of follow up (p=0,026; p=0,034). A rise in 5 or more mmHg in intraocular pressure was observed in 12 patients; half of them was in the triamcinolone group and the other half was in the group that received combined therapies (p<0,001). These cases with elevated intraocular pressure were well controlled with timolol maleate 0,5% drops. CONCLUSION: The simultaneous use of photocoagulation and intravitreal triamcinolone provided a higher gain of visual lines than the isolated use of each treatment. The laser photocoagulation was the only therapy that did not significantly reduce the macular volume and the macular thickness, however, it was also the only one that did not present cases of ocular hypertension during follow up.