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A two dimensional thermal-hydraulic analysis of a natural circulation experiment has been performed to evaluate the effectiveness of a higher order finite difference method for solving the Navier-Stokes and the energy equations. In the method, the convection terms appearing in each equation are solved by the Method of Characteristics using the third order Lagrange type polynomial as the interpolation function, and an iterative procedure is applied to solve the time derivative terms of each equation stably with second order accuracy. The analytical results have been compared with an experiment in which the temperature and the velocity distributions in the plenum region were measured with their fluctuations, and it was shown that the higher order finite difference method could simulate natural convection phenomena involving fluctuations well.

It has been suggested that analyzing the left ventricular long axis motion can result in the sensitive detection of cardiac functional disorders.To evaluate the usefulness of left ventricular long axis indices in managing patients on maintenance hemodialysis.Eighteen hemodialysis patients (mean age 51 +/- 10 years) as well as 16 healthy persons (mean age 49 +/- 9 years) were examined. Echocardiograms were recorded, and the plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured before and after a session of hemodialysis. The following parameters were measured: the left atrial diameter (LAD) and end-diastolic left ventricular diameter (LVDd) from M-mode echocardiograms, the end-diastolic LV volume (LVEDV) and ejection fraction (EF) from 2-D echocardiography, the E/A ratio from transmitral Doppler, the atrial systolic excursion of long axis motion of the mitral ring (ALAM) and maximal lengthening rate of the mitral ring toward the left atrium during the early diastolic phase (MLRe) from LV long axis M-mode echocardiograms.LAD, LVDd, LVEDV, and ALAM showed a positive correlation with plasma levels of ANP and BNP. EF, the E/A ratio, and MLRe showed a negative correlation with plasma levels of ANP and BNP. Changes in ALAM and plasma levels of ANP during hemodialysis were larger in the subgroup of ALAMor = 0.55 cm before hemodialysis than in the subgroup of ALAM0.55 cm before hemodialysis.These results indicate that the left ventricular long axis index can detect a disorder of left ventricular diastolic function, and that a hemodialysis patient whose ALAM before hemodialysis is0.55 cm is dialyzed with good volume control conditions.

N(epsilon)-(Carboxymethyl)lysine (CML), a well-characterized and major advanced glycation end product structure, is produced via a Maillard reaction by nonenzymatic glycation and/or oxidation. Although few of the carboxymethylation sites of lysine residues on proteins have been identified, it is known that the possible lysine glycation site in hemoglobin (Hb) is Lys-66 on the beta chain. We aimed to develop an assay for the Hb with a CML (CML-Hb) site specific to Lys-66 on the Hb beta chain and to determine whether the lysine residue at that site is carboxymethylated.Ala-His-Gly-Lys-Lys(CM)-Val-Leu-Gly-Ala-Phe-Ser-Cys, the peptide derived from the beta chain of human Hb, was synthesized as an immunogen, and a monoclonal antibody against the peptide was prepared. A latex immunoassay method was established using the antibody on an automatic analyzer. In this study, 20 samples from healthy subjects and 80 samples from nondiabetic patients undergoing hemodialysis (HD) were analyzed.The latex immunoassay method using the antibody correlated significantly with the ELISA method using the antibody (r = 0.95; P0.001). Between healthy subjects (n = 20) and nondiabetic HD patients (n = 80), a significant difference was seen in circulating CML-Hb (525 +/- 76 vs 778 +/- 137 pmol CML/mg of Hb; P0.0001).The latex method for the CML-Hb site specific to Lys-66 on the beta chain can measure large numbers of samples on an automatic analyzer.

Advanced glycation end products (AGEs) are a risk factor for diabetic complications. We have developed an assay method for N-(carboxymethyl)valine (CMV) of the hemoglobin (CMV-Hb), which is an AGE generated from HbA1c. Herein we describe the clinical utility of CMV-Hb measurement for the diagnosis of diabetic nephropathyBALB/c mice were immunized with carboxy-methylated Hb and monoclonal antibody raised against CMV-Hb. This antibody was characterized by a surface plasmon resonance. We developed a latex immunoassay using the antibody and measured CMV-Hb from erythrocytes in type 2 diabetic patients and healthy control subjects (age 64.6 +/- 12.0 vs. 61.1 +/- 13.2 years, NS: HbA1c 69 +/- 1.5 vs. 5.2 +/- 0.4%, P0.0001).A monoclonal antibody against CMV-Hb beta-chain NH2-terminal and an assay method for measurement for CNMV-Hb were both developed in our laboratory. CMV-Hb levels were significantly greater in the diabetic patients than in the control subjects (18.2 +/- 6.9 vs. 12.7 +/- 0.9 pmol CMV/mg Hb, P0.0001). No correlation was found between CMV-Hb and HbA1c or CMV-Hb and glycated albumin. Levels of CMV-Hb increased as the diabetic nephropathy progressed.We established an assay method for CMV-Hb and confirmed the presence of CMV-Hb in circulating erythrocytes. CMV-Hb was more prevalent in diabetic patients than in healthy subjects. Furthermore, it was significantly higher in patients with diabetic nephropathy, suggesting that the presence of CMV-Hb may be a valuable marker for the progression of diabetic nephropathy.

The concentrations of pyridinoline (Pyr), a novel marker of bone resorption, were simultaneously measured in both serum and urine samples by ion-paired high-performance liquid chromatography in 27 patients with predialysis chronic renal failure. The patients consisted of 19 males and 8 females, whose creatinine clearance (Ccr) ranged from 2.5 to 47.6 ml/min. The influence of residual renal function on serum Pyr and the clinical significance of serum and urinary Pyr were analyzed in patients with predialysis chronic renal failure. There were significant correlations between serum Pyr and serum Cr (r = 0.76) and between Pyr clearance and Ccr (r = 0.70). In addition, significant correlations were observed serum and urinary Pyr (r = 0.64) and between both serum and urinary Pyr and HS-PTH (r = 0.96 and r = 0.61, respectively) and osteocalcin (r = 0.80 and r = 0.73, respectively). However, serum bone alkaline phosphatase isoenzyme (ALP3) was correlated with neither serum nor urinary Pyr. There was no correlation between the ratio of serum Pyr/serum Cr and the metabolic bone markers (HS-PTH, osteocalcin and ALP3). There was a correlation between Ccr and urinary Pyr, although it was statistically significant (p0.1). These date led to the following conclusions: (1) serum Pyr in patients with oredialysis chronic renal failure is influenced by reduced renal function and (2) urinary pyr shows a state of bone resorption when an adegvafe level of renal function is maintained. This suggests that patients with an advanced stage of renal osteodystrophy are included among cases of predialysis chronic renal failure.

Recently, it has been noted that radical molecules participate in the pathogenesis of some of the complications associated with long-term dialysis therapy, such as amyloidosis. Since allantoin is produced from uric acid almost exclusively by the hydroxy radical, we investigated the plasma concentrations of allantoin in 71 patients with chronic renal failure who were on maintenance hemodialysis. Our specific objective was to investigate the relation of allantoin to the plasma concentrations of beta2-microglobulin and methylguanidine to evaluate the potential of allantoin as a significant parameter of the radical reaction. Although plasma allantoin was not detected in 15 healthy controls, plasma concentrations of allantoin increased markedly in all of the hemodialysis patients (42.6 +/- 37.7 nmol/mL) and wide variation was observed from 4.3 to 185.2 nmol/mL. In addition, we confirmed significant correlations between plasma concentrations of allantoin and beta2-microglobulin as well as serum concentrations of methylguanidine/creatinine and hyaluronic acid (r - 0.456, p0.0005, r = 0.313, p0.005, r = 0.368, p0.01, respectively). Although evidence for a direct link between plasma allantoin levels and amyloidosis was not obtained, the increase in the plasma concentrations of allantoin suggested its clinical significance as a parameter of the radical reaction that is thought to participate closely in the pathogenesis of dialysis-related amyloidosis. From a practical point of view, the measurement of plasma allantoin can be expected to become a significant method of measuring radical members which may be useful in the prophylaxis of some of the complications induced by free radicals.

Serum concentration of the pyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), which are markers of bone resorption, was measured by high-performance liquid chromatography in 56 patients on maintenance hemodialysis. The following analyses were conducted: 1) correlation with known markers of bone metabolism, 2) correlation with findings on bone changes on plain X-ray film, 3) elimination rates by hemodialysis, and 4) increment per day in pyridinoline after hemodialysis (delta Pyr/day). There was a very close correlation found between serum Pyr and Dpyr (r = 0.861). Both serum Pyr and Dpyr showed correlations with known markers of bone metabolism: C-PTH (r = 0.806 and r = 0.747, respectively), M-PTH (r = 0.766 and r = 0.749), osteocalcin (r = 0.717 and r = 0.693), Alp-3 (r = 0.523 and r = 0.441) and tartrateresistant acid phosphatase (r = 0.549 and r = 0.548). In addition, a correlation between the duration of hemodialysis and serum Pyr and Dpyr was observed (r = 0.426 and r = 0.318, respectively). When comparing the mean values of serum Pyr or Dpyr in three groups of patients divided according to bone changes seen on plain X-ray film, there were statistically significant differences between the group without bone changes and the remaining two groups with some bone changes (p0.05). A mean of 45.3% of serum Pyr was removed by hemodialysis. The serum Pyr level returned almost to the original concentration by the following hemodialysis. delta Pyr/day showed a close correlation with C-PTH (r = 0.656).(ABSTRACT TRUNCATED AT 250 WORDS)

A 40-year-old man was operated on for gynaecomastia, and on histological examination the enlarged breast tissue was found to contain a fibroadenoma. Fibroadenoma of the breast is extremely rare in men, and this is the first report to our knowledge of a fibroadenoma associated with idiopathic gynaecomastia.

Current studies have reported that free radical molecules had anticipated intimately with the pathogenesis of some complications specific for a long term hemodialysis. Among substances generated by free radical reaction, methylguanidine (MG) had been well known as most popular parameter in hemodialyzed patient, but allantoin (Alt) had been reported to be generated from uric acid by hydroxyradical, too. In this study, we measured serum level of Alt in long term hemodialyzed patient and analysed in the comparison with serum level of sialic acid, MG, and MG/Cr value. Serum level of Alt in patients group varied from 2.6 to 105.9 nmol/ml, which was significantly higher as compared with exclusively undetectable level in normal volunteers (n = 15). Serum level of Alt in each patient showed a significant correlation with serum level of a sialic acid (r = 0.400 p0.02). Furthermore, although serum level of Alt failed to show a significant correlation with serum level of MG, but showed a significant correlation with MG/Cr value. (r = 0.485 p0.01). In addition, higher level could be found in patient group having higher serum level of MG or MG/Cr value. Based upon those results, we proposed that a measurement of serum level of Alt could be of value in detection of free radical reaction in long term hemodialyzed patient.

The effect of recombinant human erythropoietin (rHuEPO) on the lymphocyte subpopulations of maintenance hemodialysis patients has been studied. Peripheral lymphocyte counts, lymphocyte subpopulations (Two color analysis) and PHA-induced proliferative response were measured before and after rHuEPO administration during 8 months in 22 stable hemodialysis patients (mean age 52 years, mean duration of dialysis 48 months). We could find a significant increase in the proportions of CD4+ Leu8- cells, HLA-DR+ cells, CD8+ HLA-DR+ cells, CD14+ HLA-DR+ cells and CD4+ Leu8-/CD8+ CD11b+ cells ratios after rHuEPO therapy. In addition, a significant decrease in the proportions of CD16+ CD57- cells and CD20+ cells could be found after rHuEPO therapy. These results suggest that rHuEPO administration to stable hemodialysis patients induces increases in lymphocytes categorized into helper subset groups and in activated T lymphocytes.

Thirty-one patients (26 male and 5 female patients) of non-hypercalciuric Ca stone formers were studied concerning their bone metabolism. We measured plasma free gamma-carboxyglutamic acid, plasma hydroxyproline, urinary free gamma-carboxyglutamic acid and urinary hydroxyproline as markers of bone metabolism. Plasma free gamma-carboxyglutamic acid level showed significantly higher in stone formers than normal controls (1.01 +/- 0.37 nmol/ml vs 0.39 +/- 0.13 nmol/ml). But no significant difference were observed in plasma hydroxyproline level (1.99 +/- 0.73 micrograms/ml vs 2.27 +/- 0.92 micrograms/ml), urinary free gamma-carboxyglutamic acid (52.0 +/- 17.6 nmol/mg.Cr vs 45.7 +/- 9.8 nmol/mg.Cr), and urinary hydroxyproline (3.87 +/- 2.02 micrograms/mg.Cr vs 3.33 +/- 1.63 micrograms/mg.Cr). In conclusion, these results suggest that abnormality of bone metabolism may be not a primary event in causing stone formation in these patients.

In the diagnosis of renal osteodystrophy (ROD) and the monitoring of its clinical course, several biochemical parameters have been appreciated as a useful indicators. The present investigations were designed to evaluate the clinical value of serum tartrate resistant acid phosphatase (TRACP) as an additional parameter of osteoclastic activity in ROD based upon the concept that TRACP was marker enzyme specific for osteoclast. Serum TRACP was assayed in 72 patients on long term hemodialysis and compared with conventional parameters of ROD such as ALP, Osteocalcin, Hydroxyproline. Bone change was analyzed according to Jensen's method and categorized into 4 stages. Serum TRACP was exclusively elevated and revealed a evident correlations with each parameters as follows: TRACP v. PTH-C, r = 0.501 p less than 0.01. Hydroxyproline, r = 0.429 p less than 0.05., ALP, r = 0.001., Osteocalcin, r = 0.540 p less than 0.01. In addition, TRACP value in the patients with high stage significantly higher than that in those low stage ROD. These results suggest that measurement of TRACP would be of clinical importance and useful for diagnosis of ROD in chronic maintenance hemodialized patients.

The in vitro assay of colony forming unit-erythroid (CFU-E) colony is a direct and most reliable method to evaluate a biological activity of erythropoietin (EPO). In general, two kinds of cells are employed in this assay system as an effector cell, e.g. bone marrow cell and fetal mouse liver cell, and the latter cell has more sensitivity for EPO. In this paper, a fundamental methodological process in vitro CFU-E colony formation using a fetal mouse liver cell was described in detail and sensitivity for EPO as well as reproducibility of formed colony count were checked up. In addition, an inhibitory effect was indicated in plasma, even though sampled from a healthy volunteer and it was confirmed to be eliminated sufficiently by simple pretreatment with acidification combined with boiling.

In order to evaluate an inhibitory effect of Al on haem synthesis, erythrocyte uroporphyrinogen-1-synthetase (RBC-Uro-S) activity and erythrocyte level of protoporphyrin (RBC-protoporph) were measured and compared with RBC-Al in 22 patients on maintenance hemodialysis. RBC-Uro-S activity was varied from 38 to 83 nM/ml RBC/hr 37 degrees C (54.18 +/- 12.42 nM/ml RBC/hr 37 degrees C) and a slight elevation could be found no more than in two cases. On the other hand, RBC-protoporph levels showed to be significantly elevated in many cases such as 8 cases out of 22 (36.4%). (normal subjects: 63.25 +/- 27.61 micrograms/dl RBC, HD patients: 90.0 +/- 28.35 micrograms/dl RBC). This study failed to confirm a significant negative correlation between RBC-Al and RBC-Uro-S activity, but a positive significant correlation could be found between RBC-Al and protoporphyrin levels. However we could confirm a negative correlation neither between RBC-Al and Hb values nor between RBC-Uro-S activity and Hb values. Therefore we concluded that Al-intoxication in the patients on long term hemodialysis had a definite inhibitory effect on heme synthesis, but it was by no means a major factor in pathogenesis of anemia associated with chronic dialysis.

The levels of serum Bone Gla Protein (BGP) and plasma free gamma-carboxyglutamic acid (free gamma-Gla) were measured in 36 patients on maintenance hemodialysis and compared with conventional parameters of renal osteodystrophy (ROD), such as C-PTH, intact PTH, Al-PIII and hydroxyproline levels in serum, and sigma GS/D. Even though the values of BGP were significantly elevated in patients group, 64.5 +/- 1.74 ng/ml, but the low values within normal range could be found in 3 of 36 patients, also. On the other hand, plasma levels of free gamma-Gla were markedly elevated in all cases as high as 10.40 +/- 3.10 nmol/ml in average compared to 1.29 +/- 0.37 nmol/ml (n = 15) in healthy controls. Comparative analysis of BGP with other parameters showed exclusively significant correlation as follows, C-PTH: r = 0.833 (p less than 0.01), intact PTH: r = 0.702 (p less than 0.01), Al-PIII: r = 0.771 (p less than 0.01), hydroxyproline: r = 0.462 (p less than 0.01), sigma GS/D: r = -0.407 (p less than 0.05). Respective for its higher levels, comparative analysis of plasma levels of free gamma-Gla with other parameters failed to show a significant correlation except for correlation with C-PTH (r = 0.459, p less than 0.01). Based upon these results, we could confirm a marked elevation in plasma levels of free gamma-Gla in all patients, but couldn't point out its clinical value in ROD in this study.

The effect of pulse therapy on severe secondary hyperparathyroidism related to chronic renal failure has been examined in 11 patients on maintenance hemodialysis by using an oral administration of 8 micrograms of 1 alpha(OH)D maximum per week. Throughout the 10 months of this treatment, the serum levels of intact-PTH, HS-PTH, and C-PTH were followed up. Additionally, to estimate the peak level of 1,25(OH)2D, its serum concentration at 10 hours after the 1 alpha (OH)D ingestion was measured. Results have shown that the serum levels of the intact-PTH, HS-PTH, and C-PTH were lowered in 9 of these 11 patients, two of this number especially showing a marked suppression of the serum intact-PTH to a low that was near to the normal upper limit level. In the two other cases of these 11 patients, no suppression was seen in any of serum PTH levels throughout the 10 months. In the cases that showed a good response, the 1,25(OH)2D serum concentration elevated significantly, to more than 100 pg/ml at 10 hours after the 1 alpha (OH)D intake. In contrast, in the 2 cases that showed no response, no appreciable elevation in the serum concentrations was noted. Thus, since the pulse therapy using 1 alpha (OH)D decreased the serum levels of the intact-PTH, HS-PTH, and C-PTH in 9 out of the 11 cases, we have concluded that pulse therapy using 1 alpha(OH)D is a valid therapy for secondary hyperparathyroidism in patients on maintenance hemodialysis.

This report describes an investigation of 128 patients on maintenance hemodialysis. Their serum bone Al-P isoenzyme (Al-P III) values were measured by the Rosalki method, and simultaneous estimations were made of their serum osteocalcin levels as a diagnostic indicator of renal osteodystrophy (ROD). ROD was evaluated clinically from Jensen's criteria, based on a four-stage classification of the radiographic evidence for subperiosteal resorption: no change (stage 0), minor change (stage I), and definite change (stages IIa and IIb). The serum Al-P III levels in the stage IIa and IIb patients showed significantly elevated values (p less than 0.01), i.e., 4.98 +/- 6.23 and 20.51 +/- 13.46 KAU, respectively. In contrast, their serum osteocalcin levels were not appreciably different. Patients with elevated N-PTH values of 0.30 ng/ml or more were found to have serum Al-P III levels of 20 KAU or more, and all of these patients were categorized under the stage IIb classification. It is concluded therefore that in chronic renal failure patients on hemodialysis, measurements of the serum Al-P III are highly useful for diagnosing ROD, and may also be considered as a critical parameter for assessing the indication for parathyroidectomy (PTX).

Urinary lactic dehydrogenase (LDH) activity and isozyme pattern were investigated in 38 patients with bladder tumors of various stages and grades and in 10 healthy persons. Urinary LDH activity was markedly elevated and directly correlated with histologic stage and grade of tumors. The urinary LDH isozyme pattern differed significantly from that of normal urine even in early and well-differentiated tumor cases. LDH4 and LDH5 became more prominent as the degree of the histologic stage and grade of the tumor increased. In the patients with tumors more advanced than stage T2, LDH4 and LDH5 were greater than LDH1 plus LDH2, the reverse of what is found in normal urine. As analogous result was obtained in patients with tumors of grade II or higher. No appreciable difference was found in the LDH isozyme pattern of patients with single or multiple tumors although the total activity was greater with multiple tumors. A comparison between LDH isozyme pattern in urine and in tumor tissue was evaluated in 26 patients with a good correlation (r = 0.40, P less than 0.05). Comparison of the results with urine LDH and urine cytology was attempted for each stage and grade. In 5 of 16 cases having negative urine cytology, a positive isozyme index was present and 10 of 13 cases having positive urine cytology had a positive isozyme index. These data suggest that evaluation of urinary LDH combined with urinary cytology might be of value in the diagnosis of bladder tumors and for following patients who have had bladder tumors.

The lactate dehydrogenase (LDH) activity and LDH isozyme ratio in the perfusate were investigated in perfused dog kidneys, preserved from dogs subjected to warm ischemia of varying duration prior to kidney removal. The length of this warm ischemic time exerted a marked effect on the variations in both the LDH activity and isozyme ratio. Moreover, the variations in LDH activity and isozyme ratio during the preservation were found to correlate well. On this basis, the M-component activity of the LDH isozymes and the activity of the LDH4 and LDH5 isoenzymes are proposed to represent more sensitive parameters for evaluating the tissue hypoxic damage. Our data were also analyzed retrospectively, in relation to the ability of the perfused kidney to function on autotransplantation. It was found that the amount of LDH4 and LDH5 isoenzyme activity was of great value in determining the viability of the kidney. Thus, an analysis of the LDH activity in the wash solution can provide considerable and precise information about the kidney viability as a graft.

The plasma level of Antithrombin-III (AT-III) antigen, antithrombin activity and the ratio of AT-III-heparin complex formation have been studied in 20 patients with chronic glomerulonephritis on regular hemodialysis at two occasions with 2 year interval (in 1986 and 1988), and studied as to each variation in each plasma levels, and compared with the period of length of hemodialysis-history of individual cases. A significant decrease was found not only in plasma level of AT-III antigen (25.7 +/- 4.1 mg/dl to 23.4 +/- 3.9 mg/dl), but also in antithrombin activity (90.8 +/- 11.8% to 85.2 +/- 16.8%). Moreover and ratio of AT-III-heparin complex formation was significantly reduced during two years, too (50.7 +/- 3.0% to 53.0 +/- 1.5%). Similarly, a significant negative correlation could be found on the comparison between the duration of hemodialysis and each plasma levels of AT-III antigen (r = -0.27), antithrombin activity (r = -0.33), and as well as ratio of AT-III-heparin complex formation (r = -0.34). Therefore, it was interestingly suggested the possibility that prolonged hemodialysis treatment induced a functional loss of AT-III, especially in a capacity to form a AT-III-heparin complex due to partial loss of the affinity for heparin.