京都大学 / 新制・課程博士 / 博士(医学) / 甲第23064号 / 医博第4691号 / 新制||医||1048(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 今中 雄一, 教授 伊達 洋至, 教授 中山 健夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Repeated cannulation of children during the course of treatment is distressing for the child, their family and to their nurses. Some paediatric units endeavour to minimise recannulation by employing strategies to reduce complications such as phlebitis and thrombosis formation. One strategy is to infuse low dose heparin and hydrocortisone (HEPHC). However, its effectiveness in prolonging cannula survival is inconclusive. There is also concern about the potential risks of administering these preparations to children. A randomised, controlled, blinded trial was conducted that examined the effectiveness of continuous infusion of low dose HEPHC in a group of children requiring long term intravenous antibiotics in a general paediatric unit. Comparisons of cannula complications and cannulae survival times were made in children receiving either continuous infusions of clear fluids or low dose HEPHC. The results demonstrated that there was no statistically significant difference (Logrank statistic=l.l, p=0.3) in cannula survival times between the two groups. It was also found that the bacterial and fungal colonisation of cannula for these children was extremely low. Based on these findings it is recommended that routine administration of low dose HEPHC to extend cannula survival time be discontinued. The findings also support current practice of removing cannula in children only when a complication occurs on completion of treatment.

Objetivo: Determinar la eficacia y seguridad de la técnica de doble guía en pacientes con canulación difícil durante una CPRE. Materiales y métodos: El presente estudio se realizó, entre el mes de enero del 2015 y julio del 2016. Se procedió a sintetizar la data, de éxito y complicaciones de la TDG en pacientes con canulación difícil y cuando la inserción de la guía en el conducto pancreático fue hecha involuntariamente después de una técnica estándar. Resultados: 24 pacientes sometidos a una CPRE con TDG; 17 fueron mujeres (70,8%) y 7 varones (29,2%). La edad promedio fue 65,21±16,49 años. La indicación más frecuente fue coledocolitiasis en 62,5 %, luego colangiocarcinoma, 12,5 %. El diagnóstico final post CPRE, fue coledocolitiasis en 45,8%, seguido por fibrosis de papila, 29,2%. El éxito de la técnica de la doble guía fue de 87,5%. Hubo 3 casos de canulación frustra con la TDG, dos pacientes presentaron pancreatitis post CPRE (8,3%), no hubo casos de perforaciones. Conclusiones: La TDG es una alternativa eficaz a la CPRE catalogada como de canulación difícil por técnica convencional, sea cual fuere la etiología, con un alto porcentaje de éxito técnico y con una tasa baja de pancreatitis post CPRE, semejante a la reportada en otros países. / Objective: To determine the efficacy and safety of double guidewire technique in patients with difficult biliary cannulation during ERCP. Materials and methods: We conducted a retrospective cohort study of all ERCPs performed between January 2015 and July 2016. DGT was performed in patients for whom biliary cannulation was difficult and guidewire insertion into the pancreatic duct (PD) was inadvertently achieved while attempting the standard WGC technique. Results: 24 patients were enrolled with ERCP and DGT; 17 were female (70.8%) and 7 male (29.2%). The average age was 65.21±16.49 years. The most frequent indication was choledocholithiasis (62.5%), then cholangiocarcinoma (12.5%). Post ERCP diagnosis was choledocholithiasis (45.8%), and papillary fibrosis (29.2%). The success of DGT was 87.5%. Three cases of failure cannulation with the DGT were reported, two patients had pancreatitis post ERCP (8.3%), there were no cases of perforations. Conclusions: TDG, is an effective alternative to difficult biliary cannulation during ERCP with conventional methods; with a high success rate and low rate of post ERCP pancreatitis, similarly to reported in other countries.

Mob stocking is a variation of rotational stocking known for restricting a large number of animals to a small area before being moved to new grass after a few hours. This method allows a long (90-day) recovery period but was hypothesized to diminish the nutritional value of herbage relative to continuous and rotational stocking with lesser stocking density at similar stocking rates. This thesis summarizes two studies conducted in Blacksburg and Raphine, and in Steeles Tavern, VA, respectively, at a single beef cattle stocking rate of 12 animal unit months per hectare live body weight. The objectives were to: (1) compare the yield and nutritional value of herbage in pastures managed with three stocking methods, termed mob, rotational, and continuous stocking; (2) compare the abundance of seeded clover species among the stocking methods; and (3) estimate the nutritional value of herbage that is consumed by beef cattle during mob stocking using extrusa sampled from esophageally-cannulated animals. Analysis of standing herbage during two years produced several important findings. Although standing herbage mass was significantly greater in mob stocked pastures at Blacksburg and Raphine, aboveground net primary productivity in 2014 did not differ significantly among mob, rotational, and continuous stocking at any of the project locations. Herbage nutritive value did not differ significantly among stocking methods over two years at Blacksburg and Raphine; however, herbage from mob stocked pastures at Steeles Tavern contained significantly greater concentrations of crude protein in September and October relative to herbage from continuous- and rotationally-stocked pastures at those times. Differences in herbage mass likely contributed to significant differences in establishment of seeded clovers: red clover [Trifolium pratense L. Cinnamon Plus] establishment was similar among stocking methods but white clover [Trifolium repens L. Will] establishment was greater in continuously stocked pastures than mob and rotationally stocked pastures. Hand-clipped samples collected at Blacksburg in September 2014 significantly underestimated the crude protein content of the herbage selected by the steers, although the concentrations of fiber constituents in herbage did not differ significantly between clipped samples and esophageal samples. Although the nutritive value of the herbage on offer did not generally differ among stocking methods at this stocking rate, diet selected was at times less nutritious during mob stocking than continuous and rotational stocking methods. At this stocking rate, stocking method had less influence on pastures than seasonal variation in weather and plant maturity. / Master of Science

Introduction: Arterial catherer placement by a general nurse at the departments of intensive care, resuscitation and anaesthesiology is still rather exceptional, despite the fact that this competence was defined in our legal system for the first time already in 2004 by the Decree no. 424/2004 Coll. of the Ministry of Health. The authorisation to execute this highly professional operation by a nurse specialised in intensive care is generally not reflected by the employer in the job description, although it might be one of the possible ways to increase the prestige of this profession. Objectives: The main objective of the thesis was to determine the current state in the area of arterial line placement from the perspective of intensive care nurses, to quantify their interest and clarify their readiness to execute the operation. Methodology: The quantitative method of anonymous questionnaire of own design was selected for the research survey. The questionnaire was distributed in electronic way to hospitals established by the Ministry of Health, regional government or private owners. We contacted one large hospital in every region, with the exception of Prague. The research sample consisted of general nurses working at the departments of intensive care, resuscitation and anaesthesiology, who at the same...

As conexinas são proteínas essenciais e estão diretamente relacionadas à propagação do impulso elétrico no coração, à velocidade de condução bem como à gênese de muitas afecções cardíacas. Em face da circulação extracorpórea (CEC) ainda ser utilizada de forma inconsistente na medicina veterinária e devido aos poucos estudos observados na literatura sobre os efeitos provocados pelo emprego da CEC na expressão da conexina 43 (Cx43) no miocárdio, objetivou-se avaliá-la em 15 animais da espécie canina, distribuidos em três grupos (C, CEC-1 e CEC -2) sendo, respectivamente, antes de realizada a CEC, com 60 minutos após esta e 60 minutos de CEC seguida de 30 minutos de restauração da perfusão espontânea. Avaliou-se a Cx43 pelas técnicas de imunofluorescência, western blot e RT-PCR em tempo real no tecido muscular cardíaco de regiões correspondentes aos átrios direito (AD) e esquerdo (AE), ventrículos direito (VD) e esquerdo (VE) e septo transverso. Os resultados indicaram a presença da Cx43 em todas as regiões do miocárdio nos grupos C, CEC-1 e CEC-2. A expressão da Cx43 variou significativamente em CEC-2 no AE e VD em relação ao grupo C (p<0,05). A expressão gênica de Gja1 (gene da Cx43) não apresentou diferença significativa entre os grupos estudados. Em CEC-2 identificou-se a presença de vacuolização na túnica média de artérias de pequeno calibre do miocárdio. Concluiu-se também que a canulação da aorta bem como a instalação do circuito de CEC no modo aorto-bicaval constitui técnica exequível / Connexins are essential proteins that are directly associated with electrical impulse propagation and speed of propagation in the heart. They also play a major role in numerous heart conditions. The use of cardiopulmonary bypass (CPB) in veterinary medicine is inconsistent and few studies describe the effect of cardiopulmonary bypass on the expression of connexin 43 (Cx43) in the myocardium. The objective of this study was to evaluate myocardial expression of Cx43. Connexin 43 of 15 dogs was assessed at 3 moments: prior to CPB (Group C); 60 minutes after CPB (Group CPB1); and 60 minutes after CPB followed by 30 minutes of spontaneous perfusion (Group CPB2). Assessment of Cx43 included immunofluorescence, western blot and RT-PCR real time of heart tissue samples from the right atrium (RA), left atrium (LA), right ventricle (LV), right ventricle (RV) and transverse septum. Our results showed the presence of Cx43 in all 5 areas of the myocardium in groups C, CPB1 and CPB2. A significant variation on the expression of Cx43 was observed when CPB2 LA and CPB2 RV were compared to group C (p<0,05). Expression of Gja1 (gene for Cx43) did not vary significantly among the study groups. Group CBP2 presented vacuolation of the tunica media of small myocardial arteries. We conclude that cannulation of the aorta and aorto-bicaval setup of the CPB circuit is feasible technique

Introduction: Neurological complications and stroke in association with cardiac surgery is a serious problem. The stroke event can occur during surgery (early stroke) or in the postoperative period with a symptom free interval (delayed stroke). Particle embolization due to aortic manipulation during surgery has been suspected as a mechanism for early stroke. The present thesis address mechanisms and survival effects of stroke both clinically (I-III) and experimentally (IV-V). Methods: Study I) Within a cohort of 2641 consecutive cases, a group of cardiac surgery patients with stroke and evaluated by computed tomography (CT) were studied (n=77). CT-findings were analyzed in relation to stroke symptoms. Study II) Data from 9122 patients undergoing coronary surgery were analyzed. Records of patients with any signs of neurological complications were reviewed to extract 149 subjects with stroke at extubation (early, 1.6%) versus 99 patients having a free interval (delayed, 1.1%). Early and delayed stroke were evaluated separately. Independent risk factors for stroke were analyzed by logistic regression and survival by Cox regression (9.3 years median follow-up). Study III) Patients with early (n=223) and delayed stroke (n=116) were identified among 10809 patients undergoing cardiac and aortic surgery, both groups exposed to cardiopulmonary bypass. Stroke patients were subdivided by the hemispheric location of lesions. Subgroups were compared and their associated pre- and peroperative variables and survival were analyzed. Study IV) Aortic cross-clamp manipulation was studied in a human cadaveric perfusion model. The pressurized aorta was repeatedly cross-clamped and washout samples were collected before and after clamp maneuvers. Particles in the washout samples were evaluated by microscopy and by digital image analysis. Study V) Pig aortas were pressurized and cannulated. Washout samples were collected before and after cannulation (n = 40). Particles were deposited onto a 10-μm filter to be evaluated by microscopy and digital image analysis. Results: Study I) In the group of patients exposed to routine cardiac surgery (i.e., clamping and cannulation) and with early stroke, right-hemispheric lesions were more frequent than of the contra-lateral side (P=0.005). Patients with aortic dissections had a strong dominance of bilateral findings, which was different from the unilateral pattern in the routine-surgery group (P&lt;0.001). Study II) Early and delayed stroke did not share any risk factors. Both early and delayed stroke explained mortality in the early postoperative period (P&lt;0.001, P&lt;0.001 respectively) but also at long term follow-up (P=0.008, P&lt;0.001 respectively). For patients surviving their first postoperative year, delayed but not early stroke influenced long-term mortality (P=0.001 and P=0.695, respectively). Study III) Stroke lesions in association to cardiac surgery were near exclusively ischemic. Early stroke had a preponderance for right-hemispheric lesions (P=0.009). In contrast, patients with early stroke that had undergone surgery of the aorta with circulatory arrest showed a pattern with more bilateral lesions compared to ‘cardiac-type’ operations (P&lt;0.001). Patients with bilateral lesions had a dramatically impaired survival compared to those with unilateral lesions (P&lt;0.001). Study IV) In the cadaveric perfusion model, cross-clamping produced a significant output of particles, which was seen for size intervals of 1 mm and smaller (P=0.002 to P=0.022). In all size intervals the particle output correlated with the degree of overall aortic calcification (P =0.002 to P=0.025). Study V) At cannulation of the pig aorta, more particles were noted after cannulation compared to before the maneuver (P&lt;0.001). This increase included small (&lt;0.1 mm, P&lt;0.001) and intermediate-size particles (0.1-0.5 mm, P&lt; 0.001). Particles above 0.5 mm were few and were not associated with cannulation. Conclusions: The influence of stroke on mortality was devastating, for both early and delayed stroke. These two stroke groups had obvious differences in both their risk factors and their hemispheric distribution. It is here emphasized that early and delayed stroke should be considered as two separate entities with suggested mechanistic differences. Ischemic lesions accounted for near all stroke events seen in association to cardiac surgery. For early stroke, these were mostly located within the right hemisphere. Results from the experimental studies underscore microembolic risks associated with aortic manipulation.

As conexinas são proteínas essenciais e estão diretamente relacionadas à propagação do impulso elétrico no coração, à velocidade de condução bem como à gênese de muitas afecções cardíacas. Em face da circulação extracorpórea (CEC) ainda ser utilizada de forma inconsistente na medicina veterinária e devido aos poucos estudos observados na literatura sobre os efeitos provocados pelo emprego da CEC na expressão da conexina 43 (Cx43) no miocárdio, objetivou-se avaliá-la em 15 animais da espécie canina, distribuidos em três grupos (C, CEC-1 e CEC -2) sendo, respectivamente, antes de realizada a CEC, com 60 minutos após esta e 60 minutos de CEC seguida de 30 minutos de restauração da perfusão espontânea. Avaliou-se a Cx43 pelas técnicas de imunofluorescência, western blot e RT-PCR em tempo real no tecido muscular cardíaco de regiões correspondentes aos átrios direito (AD) e esquerdo (AE), ventrículos direito (VD) e esquerdo (VE) e septo transverso. Os resultados indicaram a presença da Cx43 em todas as regiões do miocárdio nos grupos C, CEC-1 e CEC-2. A expressão da Cx43 variou significativamente em CEC-2 no AE e VD em relação ao grupo C (p<0,05). A expressão gênica de Gja1 (gene da Cx43) não apresentou diferença significativa entre os grupos estudados. Em CEC-2 identificou-se a presença de vacuolização na túnica média de artérias de pequeno calibre do miocárdio. Concluiu-se também que a canulação da aorta bem como a instalação do circuito de CEC no modo aorto-bicaval constitui técnica exequível / Connexins are essential proteins that are directly associated with electrical impulse propagation and speed of propagation in the heart. They also play a major role in numerous heart conditions. The use of cardiopulmonary bypass (CPB) in veterinary medicine is inconsistent and few studies describe the effect of cardiopulmonary bypass on the expression of connexin 43 (Cx43) in the myocardium. The objective of this study was to evaluate myocardial expression of Cx43. Connexin 43 of 15 dogs was assessed at 3 moments: prior to CPB (Group C); 60 minutes after CPB (Group CPB1); and 60 minutes after CPB followed by 30 minutes of spontaneous perfusion (Group CPB2). Assessment of Cx43 included immunofluorescence, western blot and RT-PCR real time of heart tissue samples from the right atrium (RA), left atrium (LA), right ventricle (LV), right ventricle (RV) and transverse septum. Our results showed the presence of Cx43 in all 5 areas of the myocardium in groups C, CPB1 and CPB2. A significant variation on the expression of Cx43 was observed when CPB2 LA and CPB2 RV were compared to group C (p<0,05). Expression of Gja1 (gene for Cx43) did not vary significantly among the study groups. Group CBP2 presented vacuolation of the tunica media of small myocardial arteries. We conclude that cannulation of the aorta and aorto-bicaval setup of the CPB circuit is feasible technique

No presenta resumen. / Revisión por pares

Objective:Iatrogenic acute limb ischaemia in paediatric patients is a well-recognised complication of vascular access. This retrospective review of a paediatric intensive care unit identified patients who developed iatrogenic acute limb ischaemia between January 2008 and July 2013. Methods: The medical records of inpatients diagnosed with acute limb ischaemia during the study period were reviewed. Patients with other causes of acute limb ischaemia were excluded. A descriptive analysis of demographics, primary diagnosis, type of vascular access used, affected anatomical region, clinical presentation, type of therapy, type of block, response to intervention used and outcomes was conducted. Results:A total of 28 patients presented with signs of acute limb ischaemia, of whom 28.6% were aged <30 days, 46.4 % were between one and 12 months and 25% were between one and five years old; 78.6% of the affected limbs were lower limbs. Four patients had resolution of ischaemia upon removal of the vascular access devices. 23 patients received various forms of pharmacological sympathectomy, in addition to conservative therapy. One patient had missing data on the type of sympathectomy that was done. The response to the sympathectomies was: 60.9% good, 8.7% moderate, 8.7% poor and in 21.7% no responses. Documented tissue loss related to the ischaemia occurred in six (21.4%) of the 28 patients. Conclusions: Iatrogenic acute limb ischaemia in children are usually managed without surgical intervention. Pharmacological sympathectomies lead to increased blood flow to the affected limb via vasodilatation of collateral vessels, with an added advantage of reducing ischemic pain. The improved blood flow is postulated to avoid and/or minimise the amount of tissue loss. Pharmacological sympathectomies may, thus, have a role to play in th e management of iatrogenic acute limb ischaemia in the paediatric population.