Experimental corneal Alkali Wound Healing(Acta Ophthalmologica Supp 187 Vol.66.1988) : 정장현

정장현 Karolinska Institutets Medicinska Fakultet 1989 해외박사

본 박사학위논문은 총9편의 국제잡지게재논문으로 구성되며 8편의 개별논문과 1편의 Review a- rticle로 구성도어 있다. 각막의 알칼리화상 치유과정에 대하여 토끼와 원숭이를 이용하여 IN NaO신5. 5mm크기으리 filter paper 를 60초간 각막에 접촉한 후 2-6개월간의 경과관찰을하며 상피,각,내피세포의치유과정을 정량적으로 분석하였다. 토끼에서 상피세포치유과정은 손상면적에의 한 창속도 관찰과 조직학적 소견을 추적하여 2-phase healing과 bliter formation을 규명하였다. 각막유는quantitative microradiography를 이용하여 dry weight 측정을 시행하였으며 2-phase healinransiednt dry weight recovery를 보고하였다. 내피세포의 치유과정은 Alizarin red 와 tryphan 색을 하여 wound area marphometry 를 시행하고조직학적관찰을 병행하여 2-phase healing 과 Secendothelial breakdown을관찰하였다. 결론적으로 토끼에서는 2-phase healing process 즉 initiat-term healing과 late long-term healing을 규명하였으며 원숭이에서는 동량의 각막손상에도 불1-phase healing이 규명되었다. 또한 상피, 각막실질,내피는 치유과정에서 서로 interdependent프傷【�도 내피의 역할이 가장 중요한점을 보고 하였다. 상기 요약한 Experimental Model을 이용�ium hyaluronic acid와 EGF의 치료효과를 검증하였으며 각 물질의 relative effect 는 각각 보�

Peritoneal transport characteristics with different dialysis solution: Clinical and experimental studies : Park, Min Sun

Park, Min Sun Karolinska Institutets Medicinska Fakultet 1995 해외박사

본 연구에서 여러 가지 복막투석액 사용에 따른 복막 투과성의 특성을 복막 투석 환자와 실험동물에서 조사하여 복막 투석의 기전을 밝히고자 하였다. 첫번째 실험에서는 임상에서 가장 흔히 사용되는 포도당을 포함하는 투석액 과 말기신부전환자에서 흔히 발견되는 negative nitrogen balance를 교정하기 위하여 고안된 아미노산을 포함한 투석액 사이의 복막을 통한 초여과율, 당, creatinine, BUN, 나트륨, 칼륨, 아미노산의 이동을 조사 하였다. 두번째 실 험에서는 임상에서 수행할 수 없는 과제를 수행하기 위하여 임상의 복막 투석 과 복막 투석 모델을 정상 흰쥐에서 시행하여, 임상 결과와 비교 분석하여 동 물 실험 시 임상 결과와 초여과율과 urea의 이동은 대체로 유사하나 당, 나트 륨, 칼륨의 이동에는 괄목할 만한 차이가 있음을 발견하여 동물 실험의 분석 에 지표를 마련하였다. 임상에서 삼투 물질로 흔히 사용되는 포도당은 cryst alloid osmosis에 의해 초여과를 초래한다. 그러나 포도당은 확산에 의해 체내로 흡수되고 따라서 시간에 따라 초여과율이 감소한다. 알부민은 이상적 인 colloid osmotic agent로 알려져 있고 복강을 통한 알부민의 흡수는 미미 하다. 따라서 알부민을 삼투물질로 사용하면 지속적이고 안정적인 초여과율 을 기대할 수 있다. 이에 3번째 연구에서는 알부민을 삼투 물질로 사용 하였 을 때 초여과능을 조사하여 7. 5% 알부민 투석 액이 4시간 이상 지속적으로 초 여과율을 유지하고, 특히 알부민과 당을 같이 사용하면 높은 초여과율을 장시 간 유지할 수 있어, crystalloid colloid의 동시 사용 가능성을 제시 하였다. 복막 투석 시 용질의 이동은 주로 확산에 의한 것으로 알려져 있다. 그러 나 고농도의 당을 포함하는 투석액을 사용하면 전체 용질의 이동의 약 1/3은 대류(convection)에 의한다. 4번째 연구에서는 투석액 내, urea, creatinine , 나트륨, 칼륨의 농도를 혈중 농도와 유사하게 하여 확산에 의한 이동을 방 지하고 대류에 의한 용질의 이동을 계산 하였다. Thesis by Mitt Sun Park, 1995, Karolinska Institute, Division of Renal Medicine and Division of Baxter Novum, Department of Clinical Sciences, Huddinge University Hospital, S-141 86 Huddinge, Sweden This study was undertaken to characterize the effect of various osmotic agents on peritoneal transport characteristics (I, III), to assess the numeral values of the convective transport parameter (sieving coefficient) for small solutes (IV) and the effect of acidity in dialysis solution on the peritoneal transport characteristics (V). The study was initially perfortned in CAPD patients. To evaluate various aspects of peritoneal uansport characteristics which are not easily accessible in clinical studies, an experimental model of peritoneal dialysis in rat was initiated (II). The major findings are: I. Amino acid-based dialysis solutions have a similar effect on ulnatiltration compared with corresponding glucose-based conventional dialysis solutions. The absorption of 72-78 % of instilled amino acids was more than sufficient to compensate for the reported daily loss of amino acids during peritoneal dialysis with glucose containing solutions. Although the peritoneal transport of investigated solutes, except amino acids and urea, were not different with the amino acid solutions compared with the corresponding eqnimolar glucose solutions, the transport of amino acids and urea, were altered with PDA 2.7% versus PDA l%, suggesting an effect of the hypertonic amino acid solution on the peritoneal membrane fransport properties. II. The experimental model of peritoneal dialysis in the rat yielded consistant and reproducible results which seem to provide an appropriate basis for comparisons with peritoneal transport data in CAPD patients. However, substantial differences in peritoneal fluid and solute transport were also noted. Understanding of similarities and differences of peritoneal transport properties in an experimental peritoneal dialysis compared with data obtained from CAPD patients could be of value to interpret experimental data. III. The uanscapillsry ultrafiltration with the approximately isotonic 7.5 % albumin solution was maintained for at least for 4 hours during peritoneal dialysis in rats, although the transcapillary ultrafiltration rate was not big enough to compensate for the peritoneal fluid reabsorption rate. A dialysis solution which contained both albumin and glucose resulted in higher and more prolonged ultrafiltration than that with the equimolsr glucose-based dialysis solution without albumin. After 4-hour dialysis with the two albumin solutions, approximately 20-25 % of the initial amount of albumin was absorbed (whereas approximately 85 % of the initial amount of glucose was absorbed with Dianeal 1.36 % solution). The present study shows the beneficial effect of a large molecular solute with or without a small molecular solute as osmotic agents in the same solution for prolonged uluafiltration and prevention of glucose load during peritoneal dialysis. IV. The net sieving coefficients (S) for urea and sodium were between 0 and 1 in the rats, and did not differ from the previously reported S values measured in CAPD patients for an isochratic solution, except S for glucose which appeared to be lower. S for potassium was negative and thus ant of physical range. The finding of anomalous transport of potassium may indicate that the transport of potassium from the peritoneal cavity is not only by simple passive diffusion but also by other transport mechanisms such as active transport of potassium into cells. V. The findings that transport of fluid, glucose, sodium and potassium during the dialysis with neutral dialysis solutions was different from the values with conventional dialysis solutions suggest that the acidity of the conventional dialysis solution may influence the peritoneal transport characteristics of the investigated small solutes with exception for urea. Key words: peritoneal dialysis, experimental model of peritoneal dialysis, peritoneal nansport, kinetic modelling, ultrafiltration, diffusive uansport, convective transport, sieving coefficient, osmotic agent, acidity of dialysis solution, amino acid, albumin

Impact of peritoneal solute transport rate on nutritional status and clinical outcome in peritoneal dialysis patients

정성희 [Karolinska Institutets Medicinska Fakultet] 2003 해외박사

The transport characteristics of the peritoneal membrane may be influenced by inflammation and various comorbid diseases (CMD) in peritoneal dialysis (PD) patients. On the other hand, the peritoneal solute transport rate (PSTR) may influence patient characteristics such as nutritional status as well as the clinical outcome of PD patients. The aim of the present investigation was to elucidate the impact of PSTR on nutritional status and clinical outcome in PD patients. I. Malnutrition (MN) as assessed by subjective global assessment was common in Korean patients at initiation of PD. Initial MN and initial lean body mass calculated from creatinine kinetics (LBM) were independent predictors of mortality. Initial nutritional status, therefore, appears to exert a powerful influence on PD patient survival. II. At the start of PD, 49% of the patients with CMD had MN and 78% of patients with MN had CMD. MN alone was associated with a statistically insignificant increase in mortality but the combined presence of MN and CMD was associated with significantly higher mortality. This underlines the importance of CMD as a cause of poor clinical outcome in malnourished PD patients. III. At the start of PD, high transporters had a higher proportion of patients with CMD. High PSTR had a significant impact on patient survival. However, high PSTR did not affect patient survival in patients without CMD. Thus, the association between initial high PSTR and high mortality may be in part due to an increased prevalence of CMD in high transporters. IV. Patients with low residual renal function (RRF) had more often high C-reactive protein (CRP≥10mg/L). PTR correlated negatively with serum albumin concentrations and positively with serum CRP levels. Patient survival was significantly lower in the patients with low RRF, with high CRP, and with more than two of the following: low RRF, high CRP, and high PTR. In contrast, patients with high PSTR had high mortality only during the initial year on PD. These results indicate the importance of RRF and inflammation as predictors of mortality in PD patients whereas the predictive power of PSTR as such may loose its significance if these two parameters are taken into consideration. V. In patients who were assessed after on average 10.8 months of PD treatment, nutritional variables, 24-h total fluid removal (TFR), Kt/V_(urea), and creatinine clearance (CCr) were not different between the different transport groups. TFR correlated with D/P Cr, serum albumin, protein intake, LBM, Kt/V_(urea), and CCr. Patients with high CRP had a higher proportion of patients with reduced (<1000 ml) TFR compared to patients with normal CRP (38% vs. 16%, p=0.04). Two-year patient survival rates from the time of the assessment were not different between the different transport groups. Inflammation was an independent predictor of mortality. These results indicate that a high PSTR as such should not be regarded as a relative contraindication for PD. Instead, the results suggest that more attention should be given to inflammation and inadequate fluid removal as predictors of mortality in PD patients. VI. During the 1st year on PD, patients with increased PSTR had a low RRF and more often high CRP compared to patients with decreased or unchanged PSTR. Patients with a decrease in RRF>1.9 ml/min during the 1st year on PD had more often high CRP, higher D/P Cr, and higher changes in D/P Cr compared to the patients with a decrease in RRF≤1.9 ml/min. High CRP and low RRF were independent factors associated with PSTR during the 1st year on PD. Thus, it is possible that inflammation may cause both an increase in PSTR and a decline in RRF, or that the decline in RRF and the increase in PSTR may induce or aggravate inflammation.