京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22352号 / 医博第4593号 / 新制||医||1042(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 稲垣 暢也, 教授 森田 智視, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Chronic Venous Insufficiency (CVI) is a disease of the lower limbs that affects millions of people in the United States. It is categorized by constant venous hypertension, which can lead to swelling of the legs, pain, skin changes and ulcers. One of the widely known symptoms that can lead to CVI is varicose veins. The main source of the problem of CVI is incompetent venous valves. The purpose of venous valves is to direct blood through the veins to the heart and prevent retrograde flow to the lower limbs. CVI can be caused by leg injury, pregnancy, genetics, age, and prolonged standing. Current treatments of the disease include compression stocking therapy, ablation, vein stripping, and valve reconstruction. CVI has become such a problem for patients, especially those with secondary incompetence in the deep veins, because the current treatments are used to alleviate the symptoms of the disease but do not treat the source of the problem. One solution that has great potential is to create an implantable venous valve that could restore function of the venous system. In the past many prosthetic venous valves have been made, but none are clinically used because of problems with biocompatiblility, thrombogenicity caused by high shear rates, and longterm functionality that has been hindered by leaflet stiffening. The purpose of this research was to create a venous valve that could overcome these difficulties. This was done by designing the valve out of carbon-infiltrated carbon nanotubes (CI-CNTs). This material has been proven to be thrombo-resistant, biocompatible due to its non-reactive properties, and durable. The valve was designed to be initially open and to close with physiological pressures. The shear rate caused by implantation of the valve was minimized to reduce the likelihood of thrombus formation. FEA and CFD analysis was performed to verify the valve would function under physiological conditions and that shear rates would be in the normal range. The final design was tailored for implantation in the common femoral vein. It had a diameter of 12.7 mm, length of approximately 40 mm, and thickness of 0.3 mm. With a hydrostatic pressure of 20 mmHg it fully closed with a maximum stress of 117 MPa, which is below the ultimate strength of CI-CNTs. The CFD analysis demonstrated the valve would cause a maximum shear rate of 225.1 s

The optimal timing of valve replacement surgery in chronic severe aortic regurgitation (AR) has remained a major clinical problem in the management of these patients. Although the onset of symptoms is the generally accepted indication for aortic valve replacement (AVR), the unpredictable development of pre-symptomatic left ventricular (LV) dysfunction as a result of prolonged volume overload has resulted in numerous reports attempting to formulate a risk profile for these patients. Although aortic root and LV cineangiography have been the "gold standard" for defining the severity of AR and its effect on LV performance, serial follow-up by these means is impractical. More recently numerous non-invasive measures of LV size (echocardiogram) and function both at rest and on exercise (echocardiogram and equilibrium radionuclide angiocardiography., ERNA) have been serially utilised~ In these endeavours, the thinking has been clouded by a tendency to equate these two measures and failing to appreciate that apparent preoperative LV dysfunction (particularly on exercise) may be rapidly reversible by AVR and the consequent changes in LV loading conditions. This study was a prospective, sequential evaluation of left ventricular function using both non-invasive and invasive techniques in symptomatic and asymptomatic patients with isolated chronic, severe (4+) AR at cardiac catheterisation. The aims of the study were to (I) Identify differences in the clinical, echocardiographic, resting and exercise haemodynamic and I radionuclide measures of left ventricular function in symptomatic and asymptomatic patients with chronic severe A.R. with particular reference to the incidence of presymptomatic development of left ventricular dysfunction. (II) Critically evaluate the role of exercise stress (both isotonic and isometric) in the assessment of patients with chronic severe A.R. (III) Evaluate the influence of time (sequential studies) on the haemodynamic burden in asymptomatic patients. (IV) Study the impact of successful aortic valve replacement on the reversibility of abnormal pre-operative LV function in an attempt to predict which patients would benefit from this therapeutic intervention and whether operation for symptoms alone is the correct clinical practice.

The triglyceride/high-density cholesterol-lipoprotein (TG/HDL-c) is a biomarker of cardiovascular events and mortality. In hemodialysis patients, the evidence is controversial. A systematic review was carried out in the Medline, Scopus, Embase, Web of Science, and Pubmed databases to identify the relevant cohort studies on cardiovascular events and mortality in hemodialysis patients the role of TG/HDL-c as a risk factor. Four cohort-type studies were evaluated, with a total of 52,579 hemodialysis patients. Three studies conducted in Asian populations and one study in the United States had the highest percentage of the sample (50,673 patients). The elevated TG/HDL-c ratio is associated with better survival, and there is a consistent gradual inverse association between TG/HDL-c and mortality in all analysis subgroups. In the decile categorization of the exposure variable, a 21% decrease in the risk of cardiovascular mortality and a 15% decrease in all-cause mortality in the highest decile compared to the reference group (D10 aHR = 0.79; 95% CI: 0.69–0.91 and D10 aHR = 0.85; 95%CI: 0.78–0.92). Our results show that the TG/HDL-c ratio is a protective factor for cardiovascular outcomes and mortality in the American population and a risk factor for them in the population from Asia. / Revisión por pares

Massive bilateral adrenal hemorrhage occurring in the postoperative period is an unusual but potentially life-threatening complication of any abdominal operation. The diagnosis is often difficult due to the nonspecific nature of the clinical presentation, which is easily attributable to other more common postoperative conditions. We report a case of bilateral adrenal hemorrhage resulting in acute primary adrenal insufficiency following an otherwise-uncomplicated laparoscopic cholecystectomy, which has not previously been described. An awareness of the possibility of this uncommon condition complicating laparoscopic cholecystectomy may lead to a higher index of suspicion, which is important in timely diagnosis and prompt treatment.

Cardiovascular involvement is commonly reported in various muco- polysaccharidoses. We report a first case of Sanfilippo syndrome type A in a 12-year-old white female who has developed combined progressive mitral valvar regurgitation due to prolapse and aortic regurgitation.

No description available.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19176号 / 医博第4018号 / 新制||医||1010(附属図書館) / 32168 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小川 修, 教授 柳田 素子, 教授 三森 経世 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, 2017. / Background: In spite of the contributions of cardiovascular disease (CVD) to morbidity and mortality in chronic kidney disease (CKD) worldwide, there are no studies that have looked at cardiovascular risk factors (CVRFs) and their association with cardiovascular changes in African children with CKD. Several CVRFs have been implicated in the initiation and progression of cardiovascular changes in children with CKD, and these changes have been reported even in early CKD. This study investigated CVRFs and their association with cardiovascular changes in South African children with CKD. Method: This comparative cross sectional study recruited children (5-18 years) with CKD being followed up at the Division of Paediatric Nephrology of the Charlotte Maxeke Johannesburg Hospital and the Chris Hani Baragwanath Academic Hospital. One hundred and six children with a spectrum of CKD including those on chronic dialysis (34 CKD I, 36 CKD II-IV and 36 CKD V-dialysis) were enrolled over a 12 month study period. All patients had a short history taken along with a physical examination. Blood samples for serum creatinine, urea, albumin, calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphatase, total cholesterol, haemoglobin and C-reactive protein, Vitamin D, Fibroblast growth factor-23 (FGF-23), Fetuin-A and genomic DNA studies were taken. Where feasible, transthoracic echocardiography and high resolution ultrasonography of the common carotid artery was performed. Results: The overall median age of the patients was 11 years (8-14 years), with a male female ratio of 2.1:1. Several CVRFs detected include hypertension, proteinuria, anaemia, hypercholesterolaemia and dysregulated mineral bone metabolism. The most common CVRF detected was anaemia (39.6%) and its prevalence was highest in the dialysis group when compared with the other CKD groups. The overall median (range) cIMT was 0.505mm (0.380-0.675), and was highest in patients with dialysis dependant CKD (p=0.003). The distribution of left atrial diameter (LAD) and left ventricular mass (LVM) differed significantly (p<0.05) across the different CKD groups. Abnormal LAD was seen in 10% of patients; left ventricular hypertrophy (LVH) in 27%; left ventricular systolic dysfunction in 6% and diastolic dysfunction in one patient. Mean arterial pressure and haemoglobin levels were independently associated with cIMT; hypertension was independently associated with concentric LVH; and age and hypoalbuminaemia were independently associated with eccentric LVH. Overall, the dialysis group had the highest prevalence of vascular changes, cardiac changes and associated risk factors. A skewed pattern of Fetuin-A and FGF-23 levels with medians (range) of 57.7 (0.9-225.2) mg/dL and 28.9 (0-3893.0) pg/ml respectively, were observed. The levels of these two biomarkers varied significantly between the different CKD groups (p<0.05). Fetuin-A was independently associated with abnormal LAD but no similar relationship with other cardiovascular changes and plasma levels of Fetuin-A and FGF-23 was found. Plasma FGF-23 levels correlated better with markers of bone mineralization than Fetuin-A. Eight Fetuin-A SNPs were analysed; rs2248690, rs6787344, rs4831, rs4917, rs4918, rs2070633, rs2070634 and rs2070635. We found an association between log-transformed Fetuin-A levels and the SNP rs4918 G-allele compared to the rs4918 C-allele (p=0.046) and the rs2070633 T-allele when compared to the rs2070633 C-allele (p=0.015). Markers of MBD such as phosphate and PTH levels were associated with Fetuin-A SNPs. The rs6787344 G-allele was significantly associated with phosphate levels (0.042), and the rs4918 G-allele with PTH (p=0.044). Seven deaths were recorded in the dialysis group during the study period and severe hypertension and intracranial bleed were the most common causes of death. Modifiable risk factors such as increased total cholesterol (TC) and decreased albumin levels were more commonly seen among the deceased dialysis patients. Conclusion: A high prevalence of CVRFs and cardiovascular changes were observed in the study groups, even in those with mild to moderate disease. Information obtained from the study highlights the need to address modifiable CVRFs such as hypertension, anaemia and hypoalbuminaemia in children with CKD and also the need to determine new, population specific, paediatric reference values for cIMT in healthy African children. Finally, the study was able to demonstrate differences in the relationship between Fetuin A SNPs and Fetuin-A levels and cardiovascular changes in our study population when compared with previously published data. We postulate that these differences may be due to genetic differences between our population and other population groups previously studied. / LG2018

Exocrine pancreatic insufficiency (EPI) is a major complication of cystic fibrosis. Conventional treatment involves the replacement of pancreatic enzymes and intake of a low fat diet. However, contrary to previous therapeutic strategies, a high fat diet may be beneficial in EPI patients. The present study investigated the effects of dietary supplementation with Creon 10 000 a pancreatic enzyme preparation, in conjunction with a high-fat diet, on growth performance, digestibility and absorption of fat in a pig model of EPI by the surgical ligation of the pancreatic duct in 6 male pigs (Swedish Landrace X Yorkshire X Hampshire). Following surgery, and for the duration of the experimental period, pigs were fed a high fat diet (twice daily). The experimental period lasted for 15 days during which blood, urine and faecal samples were collected. In the last 7 days of the experimental period (days 8-14), Creon 10 000 was included in the high fat meals. Urine and faecal samples were analysed for dry matter, crude protein and fat content. Plasma was used to assess the lipaemic index and the plasma lipid profiles. Treatment with Creon 10 000 significantly increased body mass (P = 0.016) and the digestibility of dry matter, crude protein as well as the co-efficient of fat absorption were also significantly improved following treatment (P<0.05). Creon 10 000 improved the lipaemic index values and significant changes in plasma free fatty acid and triglyceride concentrations were observed but not in cholesterol or high and low density lipoproteins. This study supports previous reports that the administration of pancreatic enzyme preparations together with a high fat meal is a beneficial strategy for the nutritional management of EPI.