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Biomedical subjects

Takami Miki

Publications and source records attributed to Takami Miki.

At least 37 records · Page 2Linked to original sources
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

[Bisphosphonates and bone quality].

The clinical use of drugs, which modestly increase bone mineral density, but have sufficient effects on the fracture prevention comparable to bisphosphonates, focuses on the research of the quality of the bone. Clinical investigations using micro CT, Fourier transform infrared imaging spectroscopy, quantitative computerized tomography, and/or other new modalities which support bisphosphonate treatment do not show any quality problems of the bone. In the clinical setting, evaluation of bone quality is very limited, even in the evaluation of patients treated with bisphosphonate, except evaluation by the changes of metabolic markers of bone. The new modalities such as low radiation-dose CT, sensitive MRI or ultra sonography are expected for the clinical evaluation of the changes of bone quality.

Animals↗
PubMed2005

[Acute response of serum PTH and bone markers after injection of 1alpha,25 (OH)2D3 and 22-oxacalcitrol in hemodialysis patient].

Time-course changes of serum PTH and various bone markers were compared after injection of 1alpha,25 (OH)(2)D(3) with that of 22-oxacalcitriol (OCT) in hemodialysis patients. Five patients (M/F; 3/2, mean ages of 61.6 years) were enrolled into the present study. Oral administration of vitamin D(3) derivatives was stopped at least one week before initiation of vitamin injection. After 1 week of single intravenous injection of OCT (5 microg), 1alpha,25 (OH)(2)D(3) (0.5 microg) was followed. Serum levels of intact PTH, intact osteocalcin, bone alkaline phosphatase, cross-linked N-telopeptides of type I collagen, calcium, and phosphate were measured before, 24h, and 48 h after injections of vitamin D(3) derivatives. Significant difference did not exist in time-course changes of serum PTH, any of bone markers, calcium and phosphate between after OCT and 1alpha,25 (OH)(2)D(3) injection. In conclusion, the present study may not support the presence of significant direct effect of vitamin D(3) derivatives on bone metabolism in hemodialysis patients.

Aged↗
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

[Vascular calcification in advanced secondary hyperparathyroidism].

Cardiovascular disease is one of the largest cause of mortality in maintenance hemodialysis patients. Vascular calcifications frequently encountered in hemodialysis patients. In advanced uremic secondary hyperparathyroidism model mice, vascular calcifications were observed in their aorta, by Kossa staining. This mouse model may be a useful model to study vascular calcification in maintenance hemodialysis patients.

Animals↗
PubMed2005

[Chronic GVHD with polymyositis after non-myeloablative stem cell transplantation].

A 57-year-old man underwent an autologous hematopoietic stem cell transplant for mantle cell lymphoma in August 1999. Anemia and thrombocytopenia appeared in November 2001. He was diagnosed with further hematological examination as having acute myeloid leukemia with multilineage dysplasia following secondary myelodysplastic syndrome. He received the allogeneic hematopoietic stem cell transplant from his HLA DRB1 locus mismatched brother in May 2002. The nonmyeloablative preparative regimen consisted of fludarabine 30mg/m2 for 6 days and busulfan 4mg/kg for 2 days. Eosinophilia, decrease of lacrimal fluid and liver dysfunction appeared on Day 104. We diagnosed this as chronic GVHD and treated the patient with prednisolone 10 mg/day. Thereafter, his chronic GVHD gradually improved. He had fever and myalgia in the extremities and lumbar region with elevated serum CPK and aldolase in January 2003. Histological examination led to a diagnosis of polymyositis simultaneously with chronic GVHD. Prednisolone 50 mg/day as an initial dose was started for the polymyositis following which the prednisolone dose was gradually tapered off. The polymyositis improved promptly after the administration of prednisolone and remains in remission with a current maintenance program of prednisolone 5 mg/day.

Chronic Disease↗
PubMed2004

The clinical significance of serum osteocalcin and N-terminal propeptide of type I collagen in predialysis patients with chronic renal failure.

Several new serum markers for bone metabolism have recently become available and are being applied to clinical practice. Their clinical usefulness in predialysis patients with chronic renal failure (CRF), however, has not yet been determined. Serum levels of three bone formation markers-bone alkaline phosphatase (BAP), osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP)-and three bone resorption markers-type I collagen cross-linked N-telopeptide (NTx), deoxypyridinoline (DPD), and pyridinoline (PYD)-were measured simultaneously in 85 predialysis CRF patients (serum creatinine 3.5 +/- 1.9 mg/dl, 61.0 +/- 10.9 years old, 54 males and 31 females, 36 diabetics and 49 nondiabetics) to examine the relationships between these markers and bone mineral density (BMD) of the distal radius, as measured by peripheral quantitative computed tomography (pQCT). Trabecular BMD, which is strongly affected by bone metabolism, was significantly negatively correlated with each of the bone formation markers (r=-0.341, p=0.0016, for OC; r=-0.314, p=0.0036, for PINP; r=-0.238, p=0.0315, for BAP), but there was no significant correlation between BMD and any of the bone resorption markers. In multivariate regression analyses (adjusted by age, sex, presence of diabetes, glomerular filtration rate, intact parathyroid hormone, calcium, phosphate, and 1,25-dihydroxyvitamin D), OC and PINP were significantly associated with a decrease in BMD, but BAP was not. In conclusion, we demonstrated that in predialysis CRF patients, BMD of the distal radius, particularly of trabecular bone, is associated with serum OC and PINP levels. OC and PINP are suggested to be possible parameters for the clinical evaluation of the effect of bone metabolism on BMD.

Alkaline Phosphatase↗
PubMed2004

A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease with spastic paraparesis.

BACKGROUND: Early-onset familial Alzheimer disease is caused by mutations in the amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes. Phenotypic diversity has been reported to be associated with various mutations in PSEN1. Various mutations of PSEN1 have been reported in cases of early-onset Alzheimer disease with spastic paraparesis. OBJECTIVE: To describe a novel mutation in the PSEN1 gene associated with early-onset Alzheimer disease with spastic paraparesis. PATIENT AND METHODS: The patient was a 27-year-old man who developed early-onset dementia with spastic paraparesis. We examined sequences of the PSEN1, PSEN2, and APP genes from the patient and his family. To detect a possible mutation effect on the production of amyloid-beta peptide (Abeta), transfected HEK293 cells were examined for Abeta42 and Abeta40 production. RESULTS: We found a novel mutation (Leu85Pro) in PSEN1. This mutation influenced the production of Abeta, resulting in a 2-fold elevation of Abeta42 production and of the Abeta42/40 ratio. CONCLUSION: To our knowledge, this is the first report of very early-onset Alzheimer disease with spastic paraparesis and with the visual variant form of the disease, which is associated with visuospatial cognitive disorder. The Leu85Pro mutation in PSEN1 was pathogenic.

Adult↗
PubMed2004

Significance of serum CrossLaps as a predictor of changes in bone mineral density during estrogen replacement therapy; comparison with serum carboxyterminal telopeptide of type I collagen and urinary deoxypyridinoline.

The newly developed Elecsys Beta-CrossLaps/serum assay measures C-terminal telopeptide of type I collagen and has thus been proposed as a reliable serum marker for bone resorption. We investigated its usefulness for monitoring the therapeutic effect of estrogen replacement therapy on bone turnover and bone mineral density (BMD) in patients with postmenopausal osteoporosis. Serum Beta-CTx decreased by 43.2% +/- 9.2% (mean +/- SD), and 55.1% +/- 7.0% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy (ERT), which was significantly greater than the respective value of urinary excretion of deoxypyridinoline (DPD) (27.8% +/- 4.1%, 34.1% +/- 4.9%, respectively) or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) assay (14.5% +/- 4.1%, 13.1% +/- 5.0%, respectively). The percent reduction in serum Beta-CTx at 1, 3, and 6 months after initiation of ERT was significantly correlated in a negative manner with the percent increase in spinal BMD at 6 months. Further, ROC analysis to determine the significance of the percent change in bone resorption markers after 3 months of ERT in predicting the gain in spine BMD after 6 months suggested that serum Beta-CTx and urinary DPD might provide a more discriminating indicator than serum ICTP. In conclusion, the findings suggest that the Elecsys Beta-CrossLaps/serum assay provides a sensitive, and thus useful, tool for assessing bone resorption state in Japanese patients.

Amino Acids↗
PubMed2004

Effect and safety of intermittent weekly administration of human parathyroid hormone 1-34 in patients with primary osteoporosis evaluated by histomorphometry and microstructural analysis of iliac trabecular bone before and after 1 year of treatment.

In order to evaluate the efficacy and safety of intermittent subcutaneous administration of 1-34 N-terminal peptide of human parathyroid hormone (hPTH 1-34), 100 units of hPTH 1-34 was subcutaneously injected once a week for 1 year in ten patients with primary osteoporsis (one male and nine females) with no qualitative abnormality of the bone according to the results of iliac crest biopsy performed previously, followed by a second biopsy after the end of the 1-year administration. Written consent of the patients for participation in the study was obtained. The mean lumbar bone mineral density (LBMD) definitely increased, by 1.8%, 3.4%, and 4.6% after 12, 24, and 48 weeks of hPTH administration, in accordance with previous clinical studies. Histomorphometric analysis after double-tetracycline labeling was completed in six patients (one male and five females) after the exclusion of those who dropped out because of adverse events unrelated to the test drug, or refusal of continuation. Examination of thin hard-tissue sections revealed no qualitative abnormalities of bone tissue or bone marrow cavity, such as osteomalacia, woven bone, or osteitis fibrosa, precluding the contribution of qualitatively abnormal tissue elements to any changes of LBMD in response to hPTH 1-34 administration. Histomorphometric measurement in the second biopsy revealed a tendency for an increase of bone volume, a significant increase of osteoid surface, and a tendency for an increase in other parameters of bone formation, compared with values obtained in the preadministration biopsy. Indices of two-dimensional microstructure obtained by microfocus computed tomography (CT) and results of node-strut analysis indicated improvement of trabecular continuity. In five patients in whom three-dimensional reconstruction images were analyzed, there were significant increases of bone volume and trabecular thickness, and a significant decrease in the trabecular bone pattern factor, a parameter related to the continuity, suggesting an improvement of the three-dimensional trabcular microstructure. Intermittent weekly subcutaneous injections of hPTH (1-34) for 48 weeks increased trabecular bone volume and improved microstructure, without causing the appearance of abnormal bone elements in primary osteoporosis.

Aged↗
PubMed2004

Roles of metabolic and endocrinological alterations in atherosclerosis and cardiovascular disease in renal failure: another form of metabolic syndrome.

Patients with end-stage renal disease have markedly increased risk for death from cardiovascular disease. Renal failure is associated with multiple metabolic and endocrinologic abnormalities, and these alterations are involved in advanced atherosclerosis and high cardiovascular risk. Increased insulin resistance index by homeostasis model assessment (HOMA-IR), a simple index of insulin resistance, was an independent predictor of cardiovascular mortality in nondiabetic patients on maintenance hemodialysis. Renal failure impairs lipoprotein metabolism leading to the atherogenic lipoprotein profile characterized by increased triglyceride-rich remnant lipoproteins such as intermediate-density lipoprotein, an independent factor of increased aortic stiffness. Non-high-density lipoprotein cholesterol, the sum of cholesterol of intermediate-density lipoprotein and other apoB-containing lipoproteins, is an independent factor associated with increased arterial thickness and a predictor of cardiovascular death in hemodialysis patients. The risk for cardiovascular death in hemodialysis patients is associated closely with hypertension and malnutrition, but not with obesity. The constellation of insulin resistance, dyslipidemia, hypertension, and malnutrition in renal failure suggests the presence of another type of metabolic syndrome promoting cardiovascular disease. In addition, vitamin D deficiency and abnormalities in calcium, phosphate, and parathyroid hormone levels increase the death risk from cardiovascular disease in renal failure. It is expected that treatment of these metabolic and endocrinologic alterations would improve the survival of patients with renal failure.

Arteriosclerosis↗
PubMed2004

Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population.

BACKGROUND: Renal failure results in deficiency of active vitamin D3 that has diverse effects on metabolism and organ functions. Treatment with active forms of vitamin D(3) ameliorates abnormalities in bone and mineral metabolism, cardiac function, immune response and others. We hypothesized that treatment with vitamin D(3) may be beneficial for survival in patients with end-stage renal disease (ESRD). METHODS: We compared the risk of death between regular users (n = 162) and non-users (n = 80) of oral 1alpha-hydroxyvitamin D3 (alfacalcidol) in a cohort of ESRD patients undergoing haemodialysis for a follow-up of 61 +/- 23 months. The daily dose of alfacalcidol ranged from 0.25 to 1.5 microg, with a median of 0.5 microg. RESULTS: The alfacalcidol users showed a lower risk of death from cardiovascular disease than the non-users in a univariate Cox model [hazards ratio (HR) 0.287, 95% confidence interval (CI) 0.127-0.649, P = 0.003], whereas the risk for death from non-cardiovascular disease was not different between the two groups. Stepwise multivariate Cox analysis showed that cardiovascular mortality was significantly associated with age, presence of diabetes mellitus and treatment with alfacalcidol (HR 0.377, 95% CI 0.246-0.578, P = 0.022). CONCLUSIONS: These results indicate that use of oral alfacalcidol was associated with reduced risk for cardiovascular death in this cohort of ESRD patients. The result of this observational study warrants further randomized controlled trials with 1alpha-hydroxy vitamin D3 to confirm the possibility that such medication improves survival of ESRD patients.

Adjuvants, Immunologic↗
PubMed2004

Arterial stiffness in predialysis patients with uremia.

BACKGROUND: Hemodialysis patients have advanced arterial wall stiffening as shown by increased aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality. We compared aortic PWV of uremic patients before starting hemodialysis treatment with that of patients on maintenance hemodialysis. METHODS: The subjects were 71 patients with end-stage renal disease (ESRD) before starting hemodialysis (predialysis group), 144 patients on maintenance hemodialysis, and 140 healthy control subjects. These three groups were all nondiabetic and comparable in age and gender. RESULTS: The hemodialysis group had greater aortic PWV than the healthy subjects, and the predialysis patients showed a still higher value than the hemodialysis group. Multiple regression analysis in the total subjects revealed that the presence of renal failure was significantly associated with increased aortic PWV independent of age, gender, blood pressure, body mass index, smoking, high-density lipoprotein (HDL) and nonhigh-density lipoprotein (non-HDL) cholesterol levels. In contrast, hemodialysis was associated with decreased aortic PWV independent of renal failure and the other factors. Further analyses in the combined uremic patients again indicated the favorable impact of hemodialysis on aortic PWV independent of the classical risk factors, use of antihypertensive medications, including angiotensin-converting enzyme inhibitors and calcium channel blockers, hematocrit, serum calcium, phosphorus, parathyroid hormone levels, and the use of calcium carbonate. Insulin resistance using homeostasis model assessment (HOMA-IR) was associated with increased aortic PWV. CONCLUSION: Aortic stiffening was present in uremic patients before starting hemodialysis treatment and no adverse effect of hemodialysis was observed, suggesting the important roles of renal failure and/or metabolic alterations secondary to renal failure in arterial stiffness in patients with uremia.

Aged↗
PubMed2004

FGF-23 in patients with end-stage renal disease on hemodialysis.

BACKGROUND: Fibroblast growth factor (FGF)-23 is a recently identified circulating factor which causes renal phosphate wasting disorders. Although the mechanism of regulation of FGF-23 secretion is unknown, plasma FGF-23 level may be regulated or affected by serum phosphate levels because of its hypophosphatemic effect. METHODS: We tested the hypothesis that plasma FGF-23 levels may be increased in hyperphosphatemia in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. We measured plasma FGF-23 levels in 158 male uremic patients on maintenance hemodialysis. Plasma samples were obtained before starting dialysis sessions to determine FGF-23 levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma FGF-23 level exhibited significant and positive correlations with inorganic phosphate, intact parathyroid hormone (PTH), corrected calcium, and duration of hemodialysis on simple regression analyses. All these associations remained significant in multiple regression analyses. CONCLUSION: Serum phosphate, calcium, and intact PTH could be regulators of FGF-23 levels in uremic patients on maintenance hemodialysis. Our results may provide new insights into the pathophysiologic effects of FGF-23 on calcium-phosphate homeostasis.

Case-Control Studies↗
PubMed2004

[Evaluation of osteoporosis treatment efficacy by bone mass measurement].

Dual energy X-ray absorptiometry contributes to the effective treatment of osteoporosis, although several conditions are required, such as use of effective drugs for bone mass, non-deformed lumbar spines, and enough periods before evaluation of the efficacy. Recent clinical works suggest amelioration of bone quality is more important than the bone mass increase for fracture prevention. But, measurement of bone mass is still essential for the evaluation of osteoporosis treatment under the circumstance that no modalities for bone quality are available clinically.

Absorptiometry, Photon↗
PubMed2003

Preferential reductions of paraarticular trabecular bone component in ultradistal radius and of calcaneus ultrasonography in early-stage rheumatoid arthritis.

Rheumatoid arthritis (RA) is a major cause of secondary osteoporosis and is frequently associated with both paraarticular and generalized osteoporosis. The present study was designed to investigate the preferential sites of reduction of bone mineral density (BMD), in the early stage of RA, with special emphasis on the differential effect of RA on BMD in trabecular and cortical components. The participants (30 RA patients and 26 healthy participants) were all female with disease duration of less than 1 year. BMD in the radius was measured at 4% (ultradistal site) and 20% (midshaft) to the ulnar length proximal to the end of radius by peripheral quantitative computed tomography. BMD in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. RA patients showed lower BMD preferentially in the trabecular component, but not in cortical bone component of the ultradistal radius than age-matched normal controls. Calcaneus OSI was also significantly reduced. The radial midshaft and lumbar spine did not differ significantly between RA patients and normal controls. Trabecular BMD in the ultradistal radius exhibited negative correlations with serum CRP, ESR, and RF, and calcaneus OSI with M-HAQ score. In conclusion, it was suggested that disease activity of RA and impairment of daily physical activity might be a significant determinant of deterioration of bone structure in paraartciular distal radius and calcaneus, respectively, in early-stage RA patients.

Activities of Daily Living↗