Palliative Liver Radiotherapy (RT) for Symptomatic Hepatocellular Carcinoma (HCC).

This study aims at evaluating the symptom response, response duration, and toxicity of single dose palliative liver radiotherapy (RT) for symptomatic HCC patients. We reviewed unresectable HCC patients treated with palliative RT in our institution. Eligible patients were unsuitable or refractory to trans-arterial chemoembolization (TACE) and stereotactic body radiotherapy (SBRT), with an index symptom of pain or abdominal discomfort. The primary outcome was the percentage of patients with clinical improvement of index symptom at 1 month. Secondary outcomes were response duration, toxicities, alpha-feto protein (AFP) response, and radiological response. Fifty-two patients were included in the study. The index symptom was pain in 34 patients (65.4%), and abdominal discomfort (34.6%) in 18 patients. At 1 month, 51.9% of patients had improvement of symptoms. Median time to symptom progression was 89 days (range: 12-392 days). Treatment was well tolerated with only 2 patients (3.8%) developing grade 3 GI toxicities. AFP response, radiological response rate, and disease control rate at 3 months were 48.6%, 15.1%, and 54.5% respectively. Half of the patients had improvement of index symptoms after receiving palliative liver RT with median response duration of 3 months. The treatment was well tolerated with minimal toxicities.

Identification of porcine circovirus type 2 in retrospective cases of pigs naturally infected with porcine epidemic diarrhoea virus.

The identification of porcine circovirus type 2 (PCV2) was studied in fresh intestinal tissues by polymerase chain reaction (PCR) and in formalin-fixed, paraffin-wax-embedded intestinal tissues by in situ hybridisation. The tissues came from pigs naturally infected with porcine epidemic diarrhoea virus (PEDV). A total of 35 (32.7%) of 107 small intestinal samples from pigs naturally infected with PEDV were found to be positive using PCR. Positive signals for PCV2 were detected in 32 (29.9%) of 107 small intestinal samples from pigs naturally infected with PEDV by in situ hybridisation. The distribution of positive cells in the jejunum and ileum was multifocal or patchy. Distinct positive labelling was found throughout the lamina propria in the small intestines. The results of this study indicate that PCV2 is highly prevalent in pigs naturally infected with PEDV.

Development of in-situ hybridization for the detection of Mycoplasma haemosuis (Eperythrozoon suis) in formalin-fixed, paraffin wax-embedded tissues from experimentally infected splenectomized pigs.

Mycoplasma haemosuis DNA was detected in experimentally infected splenectomized pigs by in-situ hybridization (ISH) with a nonradioactive digoxigenin-labelled DNA probe. An 839 base pair DNA probe targeting a 16S rRNA gene was generated by the polymerase chain reaction. Eight 6-week-old pigs were inoculated intraperitoneally with 6 ml of M. haemosuis-infected pig blood and eight negative control pigs were inoculated intraperitoneally with 6 ml of M. haemosuis-free blood. Two pigs from each group were killed for examination at 3, 7, 15 and 30 days post-inoculation (dpi). Red blood cells infected with M. haemosuis were first detected by light microscopy at 3 to 7 dpi. No M. haemosuis was observed in negative control pigs. Hybridization signals were evident in blood from the infected pigs at 3 dpi. The ISH method developed in this study was useful for the detection of M. haemosuis DNA in formalin-fixed, paraffin wax-embedded tissues and may be valuable for studying the pathogenesis of M. haemosuis infection.

Clinical outcome in continuous ambulatory peritoneal dialysis patients is not influenced by high peritoneal transport status.

OBJECTIVES: We undertook this study to examine the influence of demographics, peritoneal membrane transport characteristics, nutrition indices, dialysis adequacy, and comorbid diseases on patient survival on continuous ambulatory peritoneal dialysis (CAPD), and to identify whether high peritoneal membrane transport is an independent risk factor for mortality on CAPD. DESIGN: Our retrospective study was carried out in CAPD patients in a large tertiary care teaching hospital. METHODS: Until December 2000, we followed 212 patients who started CAPD between 1994 and 1997 and who underwent a peritoneal equilibration test (PET) within 3 months of CAPD initiation. RESULTS: By univariate analysis, comorbid diseases, old age, high peritoneal transport, and serum albumin predicted patient mortality. Independent predictors of mortality as determined by the Cox proportional hazard model included diabetes mellitus, cardiovascular disease, serum albumin, and old age. High peritoneal transport failed to independently influence mortality in our CAPD patients.

Current status of peritoneal dialysis in Korea: efforts to achieve optimal outcome.

Since its introduction in 1981, peritoneal dialysis (PD) has become firmly established as an effective mode of renal replacement therapy and serves an increasing patient population in Korea. The latest registry data indicate that about 3700 end-stage renal disease patients are maintained on chronic PD, representing 24.1% of the country's dialysis population. The majority (93.3%) of these patients are on continuous ambulatory peritoneal dialysis (CAPD) using the two-bag disconnect system, while only 3.3% are on automated PD. Under current renal reimbursement policies, most dialysis patients have to pay 20% of dialysis fees. Thus CAPD patients on 4 x 2-L daily exchanges pay about US$200 per month, not including medication and travel costs. Traditionally, most PD centers in Korea have used the "standard" prescription of 4 exchanges of 2 L of solution for most of their patients. A recent survey of 1467 patients who commenced CAPD in 1997 revealed that 84% of these patients were initially prescribed 4 x 2-L exchanges, while 12% were given a daily volume of 6 L. With this standard prescription, the percentages of Korean CAPD patients initially achieving the adequacy target of Kt/V urea > or = 2.0 and standardized creatinine clearance (SCCr) > or = 60 L/week/1.73 m2, were 74.4% and 82.1%, respectively. It is likely that, among current Korean CAPD patients, a much lower percentage will achieve the clearance targets compared to this initial outcome, but the precise data are not available. However, it is not clear whether the levels of small-solute clearance recommended for optimal PD outcomes, and proposed by the NKF-DOQI guidelines, will bring the expected benefits to Korean patients. Overall survival of Korean PD patients appears to be as good as, or even better than, that in most other countries. Recently, a single large PD center reported patient survival of 92.1%, 85.6%, 81.4%, and 67.6% at 1, 2, 3, and 5 years respectively. Other centers also reported similar outcomes. As in other countries, cardiovascular deaths predominate among Korean patients: death was due to cardiac causes in 29%, to vascular causes in 21%, and to infectious causes in 24%. Peritonitis is the most important barrier to prolonged use of CAPD in Korea, and more PD patients transfer to hemodialysis because of peritonitis than in other countries. To further reduce the morbidity and mortality of Korean PD patients, various control measures need to be implemented that can reduce or prevent peritonitis and other infectious complications. Also, to further improve long-term patient outcome, Korean nephrologists need to establish and practice optimal clearance targets in the chronic care of these patients.

Risk factors influencing the decline of residual renal function in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: To assess the nature of the decline in residual renal function (RRF) after the initiation of peritoneal dialysis, and to identify risk factors influencing the preservation of RRF. DESIGN: A retrospective single-center study. SETTING: Tertiary medical center. PATIENTS: Eighty patients who were clinically stable and had been on continuous ambulatory peritoneal dialysis (CAPD) for a minimum of 6 months. MAIN OUTCOME MEASURES: All subjects had at least three measurements of RRF, which was calculated as the average of creatinine clearance (Ccr) and urea clearance from a 24-hour urine collection. All measurements of RRF were plotted on a logarithmic scale and a linear scale against the duration of CAPD. Covariables used in the correlation analyses were age, sex, the presence of diabetes mellitus, mean blood pressure, mean diastolic blood pressure, hematocrit and Ccr at the start of peritoneal dialysis, peritoneal membrane transport characteristics by peritoneal equilibration test (PET), and the rate of peritonitis. RESULTS: A significant correlation was found between CAPD duration and RRF decline represented on a logarithmic scale with a correlation coefficient (r) of 0.355 (p < 0.001). In contrast, on a linear scale, the correlation coefficient was only 0.273 (p < 0.01). By linear multiple regression analysis, the only independent risk factor for the decline of RRF was the rate of peritonitis (r = -0.446, p < 0.001). CONCLUSION: These results suggest that RRF declines exponentially rather than linearly with time, and that the rate of peritonitis is an independent risk factor for the decline of RRF in CAPD patients.

Renal osteodystrophy in pre-dialysis patients: ethnic difference?

The purpose of the present study is to investigate whether an ethnic difference exists in the incidence of renal osteodystrophy between Asian and Western countries in end-stage renal disease (ESRD) patients. We evaluated bone histology in 58 pre-dialysis patients (28 male, 30 female; mean age: 47.7 years). All patients had bone biopsies with quantitative histomorphometry and serological parameters such as intact PTH, osteocalcin, total alkaline phosphatase, and basal and deferoxamine-stimulated serum aluminum levels. We observed that 91.4% of all evaluated patients showed renal osteodystrophy before the start of dialytic therapy. Mild osteitis fibrosa were observed in 21 patients (36.2%), severe osteitis fibrosa in 5 patients (8.6%), mixed lesions in 7 patients (12.1%), osteomalacia in 6 patients (10.3%), aplastic bone disease in 14 patients (24.1%), and normal bone in 5 patients (8.6%). Among the bone histomorphometric parameters, fibrosis area rate (%) showed the best correlation with intact PTH, and osteocalcin and osteoid area rate (%) with total alkaline phosphatase. Aluminum-related bone disease was not observed. Among patients with aplastic bone disease, only 14.3% showed aluminum deposition of any significance (5% < stainable bone surface aluminum < 25%). In the diabetic patients, aplastic bone disease was most common, but no case was related to aluminum intoxication. In conclusion, the distribution of renal osteodystrophy in our study was different from that of Western countries in pre-dialysis patients. Our patients tended to have more mild-form osteitis fibrosa and normal findings, and less severe-form osteitis fibrosa and aplastic bone disease. Aluminum-related bone disease was not observed.

Effect of captopril on heavy proteinuria in patients with various glomerular diseases.

The effect of captopril on proteinuria was evaluated in twenty patients with various glomerular diseases excreting heavy proteinuria (> 3.0 g/day). Captopril in a daily dose of 37.5 mg was administered orally three times a day to all patients and they were followed for eight weeks. Twenty-four hour urinary excretion of protein, creatinine, sodium, selective protein index (SPI), and blood chemistry including serum electrolytes were measured every two weeks. Twenty-four hour urinary protein excretion per gram creatinine started to fall within two weeks of captopril administration and became nearly stable after four weeks of therapy (p < 0.05). Mean 24-hour urinary protein excretion decreased significantly from a pretreatment value of 9.0 +/- 6.0 gm/gm of cr. to 4.4 +/- 3.5 gm/gm of cr. after eight weeks of captopril treatment. The serum albumin level increased progressively at six and eight weeks after the captopril treatment period and was significantly higher than the pretreatment value (p < 0.05). The decrease in proteinuria did not coincide with a fall in blood pressure or any changes in creatinine clearance. We conclude that captopril does have a significant antiproteinuric effect in patients excreting heavy proteinuria with various glomerular diseases. However, the long term therapeutic efficacy and any renal protective effect of this drug remain to be proven.

Fabry's disease--a case report and review of literatures reported in Korea.

Fabry's disease is a rare, X-linked disorder of the glycosphingolipid metabolism, in which a partial or total deficiency of a lysosomal alpha(alpha)-galactosidase results in the progressive accumulation of neutral glycosphingolipids with terminal alpha galactose moieties (i.e., cerebroside di- and trihexoside) in most body fluids and tissues. Accumulation of neutral glycosphingolipids occurs within the lysosomes of endothelial, perithelial, and smooth muscle cells of the myocardial and renal systems; to a lesser extent in reticuloendothelial and connective cells of the cornea; and in ganglion and perineural cells of the autonomic nervous system. In Korea, 7 cases of Fabry's disease have been reported. A 29-year-old man with fever and headache had typical skin findings and a family history of Fabry's disease, and it was confirmed through renal biopsy and enzyme assay for alpha-galactosidase. We report a case of Fabry's disease with a review of the literatures reported in Korea.

Studies on bone markers and bone mineral density in patients with chronic renal failure.

Renal osteodystrophy has become a frequent complication in patients with chronic renal failure (CRF), and various histologic forms such as high turnover, low turnover and mixed bone disease have been demonstrated. The only reliable method for distinguishing patients with high turnover from those with low turnover bone disease is bone histomorphometric study, but its clinical utility is restricted. Because of its invasive nature, efforts have been made to predict indirectly the type and severity of this metabolic bone disease by serum assays. In this cross-sectional study, we measured total and regional (head, arms, trunk, ribs, legs, spine and pelvis) bone mineral densities (BMD) by dual X-ray absorptiometry (DXA) in patients with variable degrees of CRF and correlated them with various bone markers. Decreased BMDs were detected in various skeletal sites (trunk and pelvis) in the patients' group. Total BMD Z score was lower in predialysis CRF patients than in the control subjects. Decreased BMD Z scores on weight-bearing bone were pronounced at L1 lumbar vertebra, femur trochanter, femur neck and Ward's triangle. Positive linear correlations were found between creatinine clearance and trunk, ribs, pelvis, and spine BMDs. There were inverse linear correlations between total BMD and total BMD Z score and alkaline phosphatase (AP), urine deoxypyridinoline (U-DPD) in the patients' group. There were no correlations between regional and total BMD, total BMD Z score and serum calcium, ionized calcium, and serum phosphate. There were inverse linear correlations between BUN, creatinine and bone-specific alkaline phosphatase in the predialysis CRF group. We evaluated the correlations between intact parathyroid hormone (i-PTH) and biochemical and other bone markers. There was statistically significant linear correlation between i-PTH and AP. Other bone markers have no significant correlations with i-PTH. Our results demonstrated that there is significant bone loss in patients with CRF before the start of dialysis and also regional variations of BMDs in predialysis CRF patients. DXA is a useful method for evaluating regional and total BMDs and provides information about diverse regional skeletal changes. AP, i-PTH and U-DPD can predict BMD of predialysis CRF patients.

Extrarenal manifestations of autosomal dominant polycystic kidney disease.

Recently, with the widespread use of new imaging techniques, the diagnosis of autosomal dominant polycystic kidney disease (ADPKD) is increasing. To analyze the extrarenal manifestations of ADPKD in Korean patients, we retrospectively studied the clinical characteristics of 30 patients with ADPKD. Thirty Patients with ADPKD who had been diagnosed at Yongdong Severance Hospital from 1988 through 1994 were recruited for this study. All patients' past and family histories were re-evaluated, and charts and radiologic images were reviewed retrospectively. The male to female ratio was 9:21, and the age of initial diagnosis was 39.2 +/- 13.8 (mean +/- SD) years. In 15 cases (50%), ADPKD had been diagnosed by renal symptoms; in 8 cases (26.7%), by chance during evaluation of extrarenal diseases; in 5 cases (16.7%), by family screening; and in 2 cases (6.7%), by uremic symptoms. Extrarenal involvement included hepatic cysts (70%), pancreatic cysts (16.7%), splenic cysts (6.7%), thyroid cysts (6.7%), inguinal hernia (3.3%), and colonic diverticula (3.3%). In 5 cases (16.7%), cardiac valvular abnormalities were noted by echocardiography. Seven patients underwent hemodialysis, and the duration from the initial diagnosis to initiation of dialysis was 9.9 +/- 8.5 (mean +/- SD) years. We investigated the extrarenal manifestations of 30 cases of ADPKD in Koreans, which were also common and clinically important as renal manifestations. Renal cysts are only one of a myriad of renal and extrarenal manifestations of ADPKD. ADPKD should be managed systematically since this disorder is a systemic disease with clinically important involvement of the cardiovascular system, the gastrointestinal tract, the genitourinary system, and the musculoskeletal system.

Comparative study of hepatitis C virus antibody between hemodialysis and continuous ambulatory peritoneal dialysis patients.

We have done cross sectional and prospective studies to determine the prevalence and the clinical significance of antibodies to the hepatitis C virus (Anti-HCV) in 54 hemodialysis (HD) patients and 227 continuous ambulatory peritoneal dialysis (CAPD) patients. Fifteen patients (27.8%) were anti-HCV (+) among the HD group, and twelve patients (5.3%) were anti-HCV (+) among the CAPD group. In the HD group, the positivity of anti-HCV correlated with the duration of HD, but there was no significant correlation with the history of transfusion, the amount of transfusion and abnormal alanine aminotransferase (ALT). At the follow-up study in 164 cases (HD 50 cases, CAPD 114 cases) after 6 months, one of 14 anti-HCV (+) CAPD patients was converted to anti-HCV (-) and two of 35 anti-HCV (-) HD patients were converted to anti-HCV (+). In conclusion, the prevalence of anti-HCV was significantly higher in HD patients compared to CAPD patients, and the positivity for anti-HCV in HD patients correlated with the duration of HD. A regular follow-up of anti-HCV and isolation of anti-HCV (+) HD patients with a separate machine may be needed to prevent the transmission of the hepatitis C virus during hemodialysis.

An analysis of 4,514 cases of renal biopsy in Korea.

To evaluate the distribution and changing patterns of renal diseases in Korea, a total of 4,514 cases of renal biopsy collected over a 23-year period between 1973 and 1995 were reviewed. Of 4,200 cases excluding 314 unsatisfactory biopsies, adult cases comprised 59.5% and pediatric cases, 40.5%. The male to female ratio was 1.5:1 in adults and 2.2:1 in children. Glomerulonephritis (GN) comprised 80.0% of the total. The most common primary GN in adults was minimal change disease (MCD) (26.6%), followed by IgA nephropathy (IgAN) (22.1%), membranous GN (MGN) (11.8%), and membranoproliferative GN (MPGN) (5.9%). In children, the primary GN incidence rates were MCD (24.8%), IgAN (10.3%), poststreptococcal (including postinfectious) GN (PSGN) (8.6%), and focal segmental glomerulosclerosis (FSGS) (4.0%). The most common secondary GN in adults was lupus nephritis and in children Henoch-Schonlein purpura nephritis. The most common cause of nephrotic syndrome was MCD in both adults and children, followed by MGN and FSGS. The elderly, aged sixty years and older, comprised 2.7% of cases and recorded equal numbers of MCD and MGN. The proportion of the biopsies found to be seropositive for HBs antigen was 27.9%, and these showed either MGN or MPGN pattern. Repeat biopsy was performed in 168 patients, due to previous biopsy failure in 15.5%. When the primary GN cases were analyzed at 5-year intervals, the prevalence of PSGN, which was greater than 25% during the 1973-1982 period, decreased abruptly in children thereafter, whereas the prevalence of FSGS increased slowly since the 1988-1992 period in both adults and children. The decrease of PSGN and the increase of FSGS suggest a role for socioeconomic and environmental factors in Korea.

Long-term outcome of kidney transplantation in adult recipients with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is an important cause of nephrotic syndrome and end-stage renal disease. FSGS recurrence after renal transplantation has a potentially detrimental course leading to the loss of renal function. In order to establish FSGS recurrence rates and evaluate the course of the disease on living-related-donor renal transplantation in ethnic Korean adults (> or = 18 years), we reviewed our experiences of 27 kidney transplantations with FSGS over the last 15 years. Of the 27 renal allografts, 13 were found to have recurrent FSGS by graft biopsy. In comparison with background data upon patients with and without recurrence of FSGS, the donor age of patients with recurrent FSGS was significantly higher than that of those without recurrence (median, 39 years vs 26, p < 0.05). In terms of, age at transplantation, length of dialysis period, and mode of dialysis no differences were found between recurrent and nonrecurrent cases. The graft survival rate of recipients from a kidney donor of age less than 40 years was significantly higher than that of recipients from a kidney donor of age more than 40 years, at 5 and 10 years, respectively (87% vs 33%, 41% vs 0%, p < 0.05). The association between clinical variables and recurrence was assessed by multiple logistic regression analysis, and donor age was found to be a risk factor of FSGS recurrence (p<0.05). Variables such as HLA-mismatch numbers and immunosuppression were not found to be associated. In conclusion, the recurrence rate of FSGS in adult recipients with FSGS was 48% and patients that received kidney from an older donor appear to be at higher risk of developing recurrence. The use of a renal graft from a younger donor is considered advisable for adult recipients with FSGS.

Development of an optimized protocol for the detection of classical swine fever virus in formalin-fixed, paraffin-embedded tissues by seminested reverse transcription-polymerase chain reaction and comparison with in situ hybridization.

An optimized protocol was developed for the detection of classical swine fever virus (CSFV) in formalin-fixed, paraffin-embedded tissues obtained from experimentally and naturally infected pigs by seminested reverse transcription-polymerase chain reaction (RT-PCR). The results for seminested RT-PCR were compared with those determined by in situ hybridization. The results obtained show that the use of deparaffinization with xylene, digestion with proteinase K, extraction with Trizol LS, followed by seminested RT-PCR is a reliable detection method. An increase in sensitivity was observed as amplicon size decreased. The highest sensitivity for RT-PCR on formalin-fixed, paraffin-embedded tissues RNA was obtained with amplicon sizes less than approximately 200 base pairs. An hybridization signal for CSFV was detected in lymph nodes from 12 experimentally and 12 naturally infected pigs. The sensitivity of seminested RT-PCR compared with in situ hybridization was 100% for CSFV. When only formalin-fixed tissues are available, seminested RT-PCR and in situ hybridization would be useful diagnostic methods for the detection of CSFV nucleic acid.

Admittance matrix of asymmetric piezoelectric bimorph with two separate electrical ports under general distributed loads.

The dynamic admittance matrix of the asymmetric triple-layer piezoelectric bimorph subjected to the general distributed harmonic loads as well as the flexural moments and the vertical loads at the tip are presented. The top and bottom piezoelectric layers have two separate electrical ports such that each layer can be used as either a sensor or an actuator. The variation principle is used for deriving the motion equations and the conjugate parameters that maintain the symmetry of the admittance matrix. The mechanical displacements and forces at the tip are expressed in a matrix form, which, together with the reciprocal condition, greatly simplify the analysis procedure. The derived admittance matrix under the cantilevered condition is presented by a five-by-five matrix, each row representing the relationships of the displacement and rotation at the tip, the volume averaged displacement, the separate electrical charges with the flexural moment and vertical load at the tip, the magnitude of the distributed load, and the voltages. The matrices, which reduce to simpler forms for several special cases, are then used to determine the two-port electrical admittance. It is shown that the derived admittance matrix covers the various boundary conditions, the electrical parallel and series connections, and the arbitrary lay-up, including the unimorph, used as both sensors and actuators.

Role of AMP-activated protein kinase and adiponectin during development of hepatic steatosis in high-fat diet-induced obesity in rats.

Obesity, an abnormal condition of adipose tissue, has recently been recognized as a major cause of metabolic syndromes, especially non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to examine the possible involvement of adipokines in the development of fatty liver. Sprague-Dawley (SD) rats fed a high-fat (HF) diet for 15 weeks developed increased hepatocellular vacuolation, hepatic triglyceride (TG) content and serum TG, total cholesterol and free fatty acid levels, with increases in adipose tissue mass. The serum concentration of adiponectin decreased slightly in these animals. Western blotting analysis demonstrated a decrease in the levels of AMP-activated protein kinase (AMPK) and phosphorylated-AMPK in the livers of these rats. These results indicate similarities between the diet-induced obesity rat model of NAFLD and human NAFLD, thus making the rat a useful model for the further study of NAFLD, including the interactions between adipokines and hepatic fat metabolism.