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Biomedical subjects

Eiji Ishimura

Publications and source records attributed to Eiji Ishimura.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cimetidine-induced tubulointerstitial nephritis with both MPO-ANCA and PR3-ANCA.

We describe a 75-year-old man with tubulointerstitial nephritis (TIN) with myeloperoxidase (MPO)-antineutrophil antibody (ANCA) and proteinase-3 (PR3)-ANCA. He had a slight fever and eruption with itching after taking cimetidine (prescribed after gastrectomy for gastric cancer) and he was admitted to a nearby hospital. There, he showed proteinuria, serum creatinine (sCr) of 2.9 mg/dl, and creatinine clearance (Ccr) of 44 ml/min per 1.73 m2. His MPO-ANCA titer was 267 EU, and PR3-ANCA titer was 112 EU. Abnormal concentrations in bilateral kidneys were found by gallium scintigraphy. For these reasons, he was transferred to our hospital. Percutaneous renal biopsy was performed after admission. Severe tubular atrophy, mild interstitial fibrosis, and severe mononuclear cell infiltration of the interstitium were noted. Drug-induced renal impairment was suspected, and cimetidine administration was withdrawn. Lymphocyte stimulation tests (DLSTs) were performed. The cimetidine titer was positive, at 2,537 cpm. After the withdrawal of cimetidine, the PR3-ANCA titer was reduced gradually, and, next, the MPO-ANCA titer was also reduced. The sCr level was reduced to 1.2 mg/dl. In summary, we report herein the first case of cimetidine-induced TIN associated with both MPO-ANCA and PR3-ANCA.

Aged↗
PubMed2005

C-reactive protein is a significant predictor of decrease in fat mass in hemodialysis patients.

Malnutrition and inflammation are common in hemodialysis patients, and are usually closely associated. We examined annual body fat mass changes, a possible nutritional parameter, in maintenance hemodialysis patients, and investigated the factors affecting such changes. Body fat mass of 454 hemodialysis patients (61+/-11 years, 269 males and 185 females) was measured twice by dual energy X-ray absorptiometry (DEXA), with a 12-month interval between measurements. In a total of 65 patients with hemodialysis duration of less than 1 year at the first measurement, fat mass at the second measurement had increased significantly over the course of a year (P<0.0001). In contrast, in a total of 389 patients with hemodialysis duration of more than 1 year at the first measurement, fat mass at the second measurement significantly decreased (P<0.005). In the 389 patients, significant negative correlations were seen between fat mass changes and CRP (r=-0.165, P<0.005). In a multiple regression analysis, CRP was a significant factor (beta=-0.163, P<0.005) affecting fat mass changes, independent of other confounding clinical factors (R(2)=0.127, P<0.001). These results show that body fat mass of long-term hemodialysis patients decreases after an initial increase in the first to second years of hemodialysis. In hemodialysis patients, fat mass change appears to be a parameter indicative of nutritional changes. Chronic inflammation, represented by higher CRP levels, is a significant factor affecting decrease in fat mass, and is related to poorer nutritional status.

Absorptiometry, Photon↗
PubMed2005

Altered relationship between body fat and plasma adiponectin in end-stage renal disease.

Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.

Adiponectin↗
PubMed2005

Cross-sectional association of serum phosphate with carotid intima-medial thickness in hemodialysis patients.

BACKGROUND: Although an increased serum phosphate concentration is a significant risk factor for vascular calcification, it is unclear whether serum phosphate level is a risk factor for increased arterial wall thickness in hemodialysis patients. METHODS: Using B-mode ultrasonography, we examined intima-medial thickness (IMT) of the carotid artery of hemodialysis patients and analyzed risk factors for increased IMT with regard to the effect of serum phosphate. Seven hundred sixteen hemodialysis patients were enrolled (547 patients without diabetes, 169 patients with diabetes; 441 men, 275 women; age, 60 +/- 8.5 years). RESULTS: IMT of patients with diabetes was significantly greater than that of patients without diabetes (0.859 +/- 0.250 versus 0.783 +/- 0.178 mm; P < 0.0001). For the group of all patients, IMT correlated weakly, but significantly, with serum phosphate level (r = 0.093; P = 0.0127). In multiple regression analysis of the group of all patients, greater serum phosphate level (beta = 0.166; P < 0.0001) was shown to be a significant independent risk factor for increased carotid IMT, in addition to other significant independent risk factors, including advanced age, higher blood pressure, greater non-high-density lipoprotein cholesterol level, and the presence of diabetes (R2 = 0.1119; P < 0.00001). In multiple regression analyses performed separately for hemodialysis patients without and with diabetes, greater phosphate level and advanced age were significant independent risk factors for increased IMT, independent of other confounding risk factors. CONCLUSION: These results show that in addition to advanced age, greater serum phosphate level is a significant and independent factor associated with advanced arteriosclerosis in hemodialysis patients with and without diabetes, suggesting that phosphate levels should be controlled appropriately to prevent an increase in arterial wall thickness in hemodialysis patients.

Adult↗
PubMed2005

Hyperphosphatemia and vascular calcification in end-stage renal disease.

Vascular calcification is a common finding in atherosclerosis and a serious problem in uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralization in vitro was examined. HSMC cultured in media containing normal physiologic levels of inorganic phosphate (1.4 mM) did not mineralize. In contrast, HSMC cultured in media containing phosphate levels comparable with those seen in hyperphosphatemic individuals (>1.4 mM) showed dose-dependent increases in mineral deposition. Mechanistic studies showed that elevated phosphate treatment of HSMC also enhanced the expression of the osteoblastic differentiation markers osteocalcin and osf2/Cbfa-1. The effects of elevated phosphate on HSMC were mediated by a sodium-dependent phosphate cotransporter (NPC) as indicated by the ability of the specific NPC inhibitor phosphonoformic acid to dose-dependently inhibit phosphate-induced calcium deposition as well as osteocalcin and Cbfa-1 gene expression. The NPC in HSMC was identified as Pit-1, a member of the novel type III NPCs. These data suggest that elevated phosphate may directly stimulate HSMC to undergo phenotypic changes that predispose to calcification and offers a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions. Furthermore, we examined the factors affecting peripheral vascular calcification in 332 nondiabetic hemodialysis patients. There were 45 nondiabetic patients with vascular calcification. In multivariate logistic regression, the significant factors affecting vascular calcification were advanced age, longer duration of hemodialysis, increased phosphate concentrations, male gender, and lower predialysis diastolic pressure. Our findings suggest that an elevated phosphate level may directly stimulate HSMC to undergo phenotypic changes that predispose to calcification and offer a novel explanation of the phenomenon of vascular calcification under hyperphosphatemic conditions.

Aorta↗
PubMed2005

Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function.

Hypothyroidism is associated with increased morbidity from cardiovascular disease, and an increase in serum osteoprotegerin (OPG) has recently been reported to be associated with the severity of coronary heart disease and cardiovascular mortality. The present study was designed to examine whether hypothyroidism causes an increase in serum OPG, and to determine whether levothyroxine (L-T4) replacement therapy might suppress serum OPG levels in hypothyroid patients. Fifty-three hypothyroid patients with chronic thyroiditis and age- and sex-matched normal control subjects were examined for the levels of serum OPG and plasma von Willebrand factor (vWF), a vascular injury marker. Thirty-seven of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T4 replacement therapy. Baseline OPG was significantly higher in hypothyroid patients than in normal controls (4.51 +/- 0.50 vs 3.72 +/- 0.23 pmol/l (mean +/- S.E.); P = 0.0182). In multivariate analysis, baseline OPG was significantly associated with baseline levels of TSH (r = 0.280, P = 0.0162) and vWF (r = 0.626, P < 0.0001). During one year of L-T4 replacement therapy, hypothyroid patients showed a significant decrease in OPG levels from 4.35 +/- 0.51 to 3.48 +/- 0.26 pmol/l (P = 0.0166), a level comparable to normal controls. The change in serum OPG levels during L-T4 replacement therapy was significantly and independently associated in a negative fashion with baseline vWF (r = -0.503, P = 0.0014). This study suggested that the severity of hypothyroidism and vascular injury might have important independent roles in increasing the serum OPG level in hypothyroid patients. Furthermore, it was demonstrated that a sustained euthyroid state might have the potential to decrease the serum OPG level in hypothyroid patients and that the degree of vascular injury in the hypothyroid state is independently associated with a decrease in serum OPG during a 1-year normalization of thyroid function.

Female↗
PubMed2005

Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism.

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet's effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1 transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93-99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.

Aging↗
PubMed2005

[Analysis of factors for progression of diabetic renal failure in elderly people].

AIM: To investigate the factors in the progression of renal failure in type 2 diabetes in elderly people. MATERIALS AND METHODS: The subjects were 2034 patients hospitalized for type 2 diabetes therapy at Osaka City University Hospital from 1993 to 2000. Among them, 362 patients had diabetic non-dialyzed renal failure. Moreover, 93 patients reached the endpoint of doubling primary serum creatinine values. We analyzed the factors of progression for diabetic renal failure, and divided the cohorts into two groups. One group consisted of patients 65 years old or more (higher age group, HP), and the other of patients under 65 years old (lower age group, LP). We used the Kaplan-Meier methods and Cox proportional hazard models for the analysis of the cohorts with the endpoint of doubling the serum creatinine values. RESULTS: There were no significant differences between HP and LP by the Kaplan-Meier methods for progression of renal failure. According to Cox monofactorial-analysis, hypoalbuminemia was determined to be a significant factor in the progression of renal failure in both HP and LP. In the Cox multifactorial-analysis, hypoalbuminemia was a independent significant factor in HP, but not in LP. CONCLUSION: Hypoalbuminemia is considered to be a significant factor in the progression of renal failure in type 2 diabetes regardless of age, and may be a more significant factor in elderly people.

Aged↗
PubMed2005

[Mechanism of arterial calcification with regards to atherosclerotic calcification and medial artery calcification].

Vascular calcification is a mechanism of active process, which includes inflammation and metabolism of bone formation. There are two different types of vascular calcification; atherosclerotic calcification and medial artery calcification. As seen in bone metabolism, vascular calcification is reported to be through enchondral ossification through BMP-2-Cbfa1 signal pathway, and through intramembranous ossification through BMP-2-Msx2 signal pathway. In the tissue of vascular calcification, several proteins which are related to bone and bone matrix metabolism have been shown to be present, such as bone morphogenic protein, osteoprotegerin, matrix gla protein, and osteopontin.

Arteries↗
PubMed2005

[Correlation of serum Bio-intact PTH (1-84) and parathyroid gland size in hemodialysed patients].

Bio-intact parathyroid hormone (Bio-PTH) assay, which measures exclusively intact PTH (1-84) molecule, provides a better assay for estimating parathyroid function in hemodialysis (HD) patients, whereas intact PTH (I-PTH) assay cross-react with PTH (7-84) as well as PTH (1-84). We have found that PTH (7-84) accumulated into serum of hemodialysis patients due probably to its impaired excretion into urine. We have reported that parathyroid gland size is one of major predictor for vitamin D responsiveness in secondary hyperparathyroidism. Therefore, we investigated whether serum Bio-PTH, in comparison with serum I-PTH, may provide a relevant assay to estimate parathyroid function as evidence by its correlation with parathyroid gland size on ultrasound examination.

Biomarkers↗
PubMed2005

[Clinical significance of PTH (1-84) and PTH (7-84) in patients with predialysis chronic renal failure in relation to bone metabolism markers].

Serum levels of parathyroid hormone (PTH) in predialysis patients with chronic renal failure (CRF) were measured using both the "intact PTH" and "bio PTH" assays, and serum levels of PTH (7-84) were assessed by subtracting bio PTH from intact PTH. The PTH values measured by the two assays were strongly correlated, and were also significantly positively correlated with both bone formation and resorption markers. PTH (7-84) was significantly positively correlated with both the intact PTH and bio PTH, and was also significantly positively correlated with the bone metabolism markers. There is no significant relationship between bio PTH/PTH (7-84) ratio and bone metabolism markers. In conclusion, bio PTH and intact PTH assays have similar clinical significance in predialysis CRF patients. The PTH (7-84) and even the ration of bio-PTH/PTH (7-84) have little specific clinical effect on bone metabolism.

Aged↗
PubMed2005

[Effect of calcium on N-terminal truncation of PTH in human parathyroid cells].

Serum PTH (7-84) is accumulated in patients with secondary hyperparathyroidism. It is also known that serum calcium (Ca) increases the generation of N-terminally truncated forms of parathyroid hormone (PTH). In this study, we examined whether accumulation of PTH (7-84) fraction is a parathyroid glandular origin or not by using primary cultured parathyroid cells from patients with primary and secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, indicating the ratio of PTH (1-84) to the sum of (1-84) PTH and N-terminally truncated fragment, was suppressed by increase in extracellular Ca2+ concentration for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. There is no difference between the ratios in primary and secondary hyperparathyroidism. These findings suggest that N-terminal truncation is regulated by extracellular Ca2+ concentration in parathyroid cells, but accumulation of PTH (7-84) fragments in patients with secondary hyperparathyroidism is mainly caused by uremia.

Calcium↗
PubMed2005

[Significance of serum PTH (7-84) as a reliable nutritional marker in hemodialysis patients].

To evaluate the significance of serum PTH (7-84) in hemodialysis patients, correlation of the serum PTH (7-84) level with various nutritional markers was investigated in HD patients. Serum PTH was determined in 170 male HD patients by either a Bio intact PTH assay or a second-generation intact PTH assay. The level of bone formation markers and bone resorption markers were also measured. Lean body mass in trunk region was measured by dual X-ray absorptiometry. The serum PTH (7-84) level was obtained for the difference between serum I-PTH and Bio-PTH. Serum PTH (1-84) was directly obtained from the serum Bio-PTH value. Serum PTH (7-84) correlated significantly with nutritional markers such as body weight, albumin, PCR, TAC BUN, BUN, phosphate and lean body mass in trunk, whereas PTH (1-84) only correlated with phosphate. The correlation of serum PTH (7-84) with bone metabolic markers was no less significant than that for PTH (1-84). The results suggest that serum level of PTH (7-84) may provide clinically useful information, not only of the bone metabolic state but also of the nutritional state in HD patients, in sharp contrast to the exclusive correlation of PTH (1-84) with bone metabolic state.

Biomarkers↗
PubMed2004

Decrease of arterial stiffness at common carotid artery in hypothyroid patients by normalization of thyroid function.

This study examined the effect of hypothyroidism on arterial stiffening and the effect of levothyroxine (l-T(4)) replacement. The arterial stiffness index beta (stiffness beta) and intima-media thickness (IMT), a parameter of arterial stiffening and thickening, respectively, were determined in common carotid artery (CCA) by ultrasonography in 30 hypothyroid patients before and after 1 year of normalization of thyroid function by l-T(4) replacement. Baseline CCA stiffness beta and IMT was significantly higher in the hypothyroid patients than in age- and sex-matched normal controls [9.46 +/- 0.93 vs. 8.02 +/- 0.91 (mean +/- SE); P < 0.05, 0.635 +/- 0.018 mm vs. 0.541 +/- 0.019 mm; P < 0.005, respectively]. In multivariate analysis, baseline stiffness beta was significantly associated with baseline levels of IMT (r = 0.457, P = 0.0311), FT(4) (r = -0.413, P = 0.0169), and a plasma vascular injury marker, von Willebrand factor (vWF) (r = 0.412, P = 0.0261). During 1 year of euthyroidism, 22 and 29 out of 30 patients showed significant decreases of stiffness beta and IMT to normal respective level, from 9.46 +/- 0.93 to 7.58 +/- 0.34 and from 0.635 +/- 0.018 to 0.552 +/- 0.015 mm, respectively. Change in stiffness beta during l-T(4) therapy correlated significantly in a negative manner with baseline levels of age (r = -0.465, P = 0.011) and IMT (r = -0.406, P = 0.029). Stiffness beta after but not before l-T(4) therapy showed a tendency towards a positive correlation with age. This study suggested that increases of arterial thickening, and plasma vWF, and a reduction in serum FT(4) might have an important role independently in the increased arterial stiffening in hypothyroid patients. Furthermore, it was demonstrated that sustained euthyroidism might have the potential to reverse arterial stiffening in addition to thickening in hypothyroid patients.

Carotid Artery, Common↗
PubMed2004

Significance of Bio-intact PTH(1-84) assay in hemodialysis patients.

The aim of the present study was to examine whether the newly developed bio-intact parathyroid hormone (Bio-PTH) assay, which exclusively measures the intact PTH(1-84) molecule, provides a better assay for estimating parathyroid function in hemodialysis (HD) patients, and to evaluate the factors associated with serum PTH levels measured by Bio-PTH assay and by second-generation intact PTH (I-PTH) assay. The study also examined whether Bio-PTH/I-PTH ratio, an index of the active fraction of PTH, could provide information not obtainable from simple PTH results. Serum levels of PTH were measured in 177 male HD patients, together with the bone formation markers bone alkaline phosphatase (BAP), intact osteocalcin (iOC), N-midfragment osteocalcin (N-Mid OC), and N-terminal propeptide of type I collagen (PINP), and the bone resorption markers deoxypyridinoline (DPD), pyridinoline (PYD), and beta-CrossLaps (beta-CTx). Bone mineral density (BMD) was determined twice at distal radius one-third by dual-energy X-ray absorptiometry. Serum Bio-PTH was significantly elevated in HD patients compared to normal controls. Serum Bio-PTH and I-PTH correlated significantly in a positive manner with serum bone formation markers (BAP, iOC, N-Mid OC, PINP), and resorption markers (DPD, PYD, beta-CTx), and in a negative manner with BMD and annual change therein at distal radius one-third. The degree of correlation of Bio-PTH was not significantly different from that of I-PTH. The Bio-PTH/I-PTH ratio was significantly lower in HD patients than in normal individuals, due probably to accumulation of N-truncated PTH fragments in the former. The Bio-PTH/I-PTH ratio correlated significantly in a negative manner with serum calcium (Ca) (r=-0.251, P<0.001) and nutritional marker serum urea nitrogen, protein catabolic rate and serum creatinine. Multiple regression analysis further revealed that serum I-PTH, but not Bio-PTH, was significantly associated with each of these nutritional markers, and that the Bio-PTH/I-PTH ratio was negatively associated with serum Ca. It was also found that I-PTH, but not Bio-PTH, was influenced by nutritional state. It is concluded that serum Bio-PTH assay could be of similar value to I-PTH assay in evaluating parathyroid function in HD patients and that their combined use in the form of the Bio-PTH/I-PTH ratio could provide information not obtainable from simple PTH results.

Adult↗
PubMed2004

Serum levels of C-terminal telopeptide of type I collagen: a useful new marker of cortical bone loss in hemodialysis patients.

Renal osteodystrophy is a major complication in hemodialysis patients. Measurement of serum peptide derived from the degradation of bone collagen could potentially provide an indirect estimate of bone resorption. The present study estimated the significance of the C-terminal telopeptide of type I collagen (beta-CTx) as a serum bone resorption marker in male hemodialysis patients. The mean age and hemodialysis duration of the 160 patients were 59.7 years (26-86 years) and 67.2 months (17-142 months), respectively. Bone mineral density (BMD) in the distal third of the radius was measured using dual-energy X-ray absorptiometry twice with a 2-year interval. A blood sample was collected immediately before the hemodialysis session at the time of the second BMD measurement. Other serum bone markers determined were bone-specific alkaline phosphatase (BAP) and intact and N-terminal midfragment (N-Mid) osteocalcin (OC) as bone-formation markers and serum pyridinoline (PYD) and deoxypyridinoline (DPD) as bone resorption markers. Serum beta-CTx correlated significantly in a positive manner with serum PYD, DPD, BAP, intact OC, and N-Mid OC. Serum beta-CTx, as well as PYD, DPD, BAP, intact OC, and N-Mid OC, correlated significantly with BMD in the distal third of the radius at the second measurement and with the rate of BMD reduction during the preceding 2 years. The highest quartile of serum beta-CTx was positively associated with rapid bone loss, defined as a change in the value for BMD in the distal third of the radius falling within the upper tertile of patients, in 55% of cases, and each quartile progress in serum beta-CTx increased the odds ratio of rapid bone loss by a factor of 1.73. Since the Youden index was twice as accurate for beta-CTx, BAP and N-Mid OC as for intact PTH, these bone-remodeling markers may be better risk markers of cortical bone loss than intact PTH. Inclusion in the highest quartile of PTH (above 288 pg/ml) predicted rapid bone loss with a sensitivity of only 26%. This means that the upper limit for serum PTH level recommended by K/DOQI may be too high, since 74% of cases with rapid bone loss showed serum PTH levels of below 288 pg/ml. In conclusion, serum measurement of beta-CTx may provide a new commercially viable and relevant serum assay to reflect cortical bone resorption in hemodialysis patients.

Adult↗