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Biomedical subjects

I Yuu

Publications and source records attributed to I Yuu.

11 recordsLinked to original sources

[Recent development and clinical application of bone mineral measurements].

Over the past decade, methodologies for the assessment of bone mineral density have markedly progressed, so that any sites of the skeleton now can be measured with high degree of accuracy and precision with safety. The number of devices distributed in Japan rapidly increased for the last 5 years and the total number installed nationwide reached over 7000 as with 1998. There are variety of techniques: microdensitometry (MD) or radiographic absorptiometry (RA), single X-ray absorptiometry (SXA), dual X-ray absorptiometry (DXA), quantitative CT (QCT), peripheral QCT, and quantitative ultrasonometry (QUS). There are, however, no such single technique as to fulfill the entire clinical requirements, since the time of initiation of bone loss, and the speed of bone loss are quite different from site to site of the skeleton, so that the correlations of bone density measured by each technique are not sufficiently high (gamma = 0.5-0.8) to predict BMD of other bones by measuring one bone. Since the relatively large amounts of data on the prediction of fracture (hip, spine and others) by these techniques have been accumulated, a specific guideline regarding the appropriate application of these techniques, including multiple combination measurements, should be established based on the worldwide consensus.

Bone Density

Diagnostic validity of bone metabolic markers for bone metastasis.

We measured bone resorption markers in tumor patients with and without bone metastases and evaluated the diagnostic validity of these biochemical parameters in the diagnosis of neoplastic bone involvement. On the basis of radiography and bone scintigraphy findings, subjects were divided into 3 groups, 83 patients without bone metastases (META(-)), 22 patients with 1 or 2 bone metastases (META(+)) and 22 patients with more than 3 bone metastases (META(++)). Among the biochemical markers, urinary pyridinoline (PYR), circulating C-terminal telopeptide of type I collagen (ICTP) and urinary N-terminal telopeptide of type I collagen (NTx) were especially sensitive and specific and increased significantly not only in META(++) but also even in META(+). The efficacy of several bone metabolic markers in differentiating between patients with and without bone metastases was evaluated by receiver-operating characteristic (ROC) analysis, and PYR, ICTP and NTx were proved to have high diagnostic validity (area under the ROC curve; 0.75 for PYR, 0.77 for ICTP and 0.77 for NTx). Furthermore, their odds ratios showed significantly high values for both META(+) and META(++)(to META(++); 7.91 for PYR, 5.33 for ICTP and 5.70 for NTx). On the other hand, urinary deoxypyridinoline (DPYR) and serum total alkaline phosphatase (ALP) showed relatively low sensitivities, the odds ratio of ALP in particular being insignificant. In conclusion, several bone metabolic markers were proved to be useful in the diagnosis of bone metastases in patients with malignancies, particularly PYR, ICTP and NTx had rather high diagnostic validities among all markers examined in this study.

Adult

[Detection of bone metastasis by serial measurement of C-terminal telopeptide of type I collagen in patients with malignancy].

Measurements of biochemical markers specific to bone resorption are known to be useful in evaluation of skeletal metastasis. However, most of previous studies were performed cross-sectionally and sensitivity for detection of early bone metastasis was not satisfactory. Since basal levels of bone markers differ significantly individually, longitudinal studies would be preferable to evaluate small metabolic changes such as in early skeletal metastasis. Thus, we performed serial measurements of serum c-terminal telopeptide of type I collagen (ICTP), a bone resorption marker, in patients with malignancy and evaluated its clinical significances for detection of bone metastasis, comparing with measurements of propeptide of type I procollagen (PICP) and tumor markers. In total, 43 patients (41 of them are breast cancer), serial serum samples were obtained during 0.5 to 2.4 years (mean 1.4 years). In all of nine patients, who developed bone metastasis, serum ICTP level increased, and by successful treatment to the metastatic lesions, ICTP level decreased, while in some cases, tumor markers remained to be elevated. PICP was less sensitive and specific for detection of bone metastasis. Thus, serial measurement of ICTP is suggested to be useful for detection and evaluation of therapeutic responses in patients with bone metastasis.

Biomarkers, Tumor

Age-related change of technetium-99m-HMDP distribution in the skeleton.

UNLABELLED: To understand age-related changes of whole-body and regional skeletal metabolism, it is important to investigate the mechanisms of age-related bone loss and to develop suitable treatments for it. Bone biopsies show metabolism of the particular site examined while biochemical markers for bone metabolism reflect total skeletal metabolism. Bone scintigraphy is a convenient and simple way to analyze whole-body and regional skeletal metabolism. We attempted to study and understand age-related changes in bone metabolism by quantifying the bone scan and correlating it with biochemical bone metabolic markers. METHODS: The whole-body skeletal uptake (WBSU) and tracer distribution pattern were studied in men and women by bone scintigraphy using 99mTc-hydroxy-methane-diphosphonate (HMDP). Bone scans were performed using a standard protocol and quantified by setting regions of interest (ROIs) on selected regions. WBSU and the skeletal distribution pattern were compared with simultaneously obtained serum biochemical markers. RESULTS: WBSU showed an increase with age in both sexes, but in women, uptake in the head and legs increased more relatively than in the thoracic region, while in men no such tendency was observed. Increase of WBSU and relative increase of uptakes in the head demonstrated a weak correlation with the serum levels of alkaline phosphatase and type 1 collagen metabolites. CONCLUSION: These results show an age-related increase of skeletal turnover and sex-dependent regional skeletal metabolism. The age-related changes seen in bone scintigrams might be a sign of progressive bone loss, reflecting changes in local bone metabolism.

Age Factors

Chronic intramedullary infusion of prostaglandin E2 stimulates bone formation both in the bone marrow and in the periosteum.

Prostaglandin E2 (PGE2) has a potent bone resorbing activity in vitro, but some recent studies have shown that PGE2 stimulates bone formation in vivo. The effects of PGE2 on the bone are therefore still controversial. We attempted to reveal the effects of PGE2 on bone in vivo more directly; we injected PGE2 continuously into the bone marrow and onto the periosteum and examined the local effects of PGE2 histologically or by bone densitometry. Following PGE2 infusion into the bone marrow, new bone was formed in the bone marrow around the infused site and following PGE2 infusion onto the periosteum, extensive periosteal bone formation was observed. Bone mineral content was also increased significantly in the PGE2 infused bones. The administration of cyclic AMP did not mimic the effects of PGE2. In contrast to in vitro experiments, the in vivo effect of PGE2 is predominantly to produce bone.

8-Bromo Cyclic Adenosine Monophosphate

Estimation of bone mineral density and bone loss by means of bone metabolic markers in postmenopausal women.

We have examined healthy women (51 premenopausal women and 30 postmenopausal women; age 28-59) for lumbar bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) and assessed metabolic bone markers, such as type I procollagen carboxy-terminal propeptide (P1CP), pyridinoline (PYR), deoxypyridinoline (DPYR), osteocalcin (BGP) and alkaline phosphatase (ALP). BMD was assessed once a year in three consecutive years. Correlations among the BMD, BMD changes and levels of bone markers in samples at the first DXA assessment were studied. In pre-menopausal women, none of the biochemical markers were correlated with the BMD or changes in BMD. In contrast, BMD in post-menopausal women correlated (negatively) well with levels of P1CP, DPYR, PYR and ALP declining in this order, and a significant positive correlation was observed between the rate of bone loss in postmenopausal women and the P1CP concentration. PYR and DPYR also had a tendency to correlate. Combinations of several bone markers improved the correlation. These results show that by measuring several bone specific biochemical markers in postmenopausal women, one can estimate their rates of bone loss as well as their present BMDs. The measurement of biochemical bone markers will therefore be very useful in evaluating bone status and would be applicable in screening postmenopausal osteopenia.

Adult

[Computed X-ray densitometry].

Computed X-ray Densitometry (CXD) is a semi-automated method of radiographic densitometry. X-ray photographs of 2nd metacarpal bone, taken with a reference Aluminum phantom, are analyzed by a computed-densitometric machine (Bonalyzer). X-ray films are imaged by a CCD camera and displayed in a screen automatically. By pointing distal and proximal heads of the metacarpal bone, photodensity expressed as Aluminum concentration is computed. Parameters such as metacarpal cortical index (MCI) and cumulated photodensity (sigma Gs/D) at the mid-metacarpal bone are obtained. Precision determined by 5 photographs taken every 5 week, is 2%. Correlation with lumbar BMD assessed by DXA is 0.663 in elderly patients. Using this semi-automated method, radiographic densitometry can be used for clinical purpose, such as screening of patients with osteoporosis or observation of therapeutic effects. Especially, in patients over 70, this method has advantages, since lumbar BMD assessment with DXA at this age is hampered by degenerative diseases.

Absorptiometry, Photon

[Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP)--some basic aspects of the RIA kit and clinical evaluation in various bone diseases].

A radioimmunoassay for circulating levels of the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP) was developed and can be available as a kit on a commercial base. Using the kits, we evaluated basically and clinically the assay. The assayed values were reproducible and the assay can detect as low as 0.5 ng/ml of 1CTP. In healthy volunteers, circulating level was high under age 24 and over age 46. In patients with bone metastasis, serum levels elevated even in its early stage and correlated well with clinical status. In other bone diseases, such as primary hyperparathyroidism, hyperthyroidism, post-gastrectomy, hypercalcemia of malignancy and myeloma, serum levels elevated according to their clinical conditions. In patients with chronic renal failure, serum levels were high, suggesting decrease of renal clearance of 1CTP. The circulating 1CTP levels seemed to reflect well clinical bone destructive status. A high correlation between serum 1CTP level and urinary pyridinoline (r = 0.884) was shown, whereas essentially no correlation was observed between bone formation markers such as osteocalcin and alkaline phosphatase. Thus, the measurement of circulating 1CTP seems to be a simple and sensitive method to monitor bone destruction.

Adult

[Measurement of serum concentration with radioimmunoassay for carboxyterminal propeptide of type 1 procollagen].

A radioimmunoassay kit for measurement of carboxyterminal propeptide of type 1 procollagen (P1CP) was developed and can be purchased commercially for clinical use. Using the kit, we measured serum concentration in healthy controls and in patients with bone metastasis and other various skeletal disorders. In healthy controls, serum concentration of P1CP ranged within 37-177 ng/ml under age 50, while in serum concentration of women over 50, it elevated upto 350 ng/ml. In patients with skeletal metastasis, in most of patients, it stayed within a normal range, whereas in patients with bone metastasis from prostatic cancer, it raised significantly. In some of patients with primary hyperparathyroidism or hyperthyroidism, serum concentration for P1CP was also elevated. In comparison with other serum bone metabolic markers such as osteocalcin or alkaline phosphatase, P1CP showed less occurrence of an elevation in patients with non-skeletal disease. Serum concentration of P1CP was not affected by renal function, while mild elevation was observed in patients with severely damaged liver diseases. In conclusion, the newly developed radioimmunoassay for P1CP was an excellent assay system and would provide us easily evaluation of type 1 collagen formation.

Adult

[Hypervitaminosis D].

Excessive vitamin D causes marked and prolonged hypercalcemia by accelerating intestinal calcium absorption and bone resorption. Vitamin D induced hypercalcemia includes the toxic ingestion of excessive amount of vitamin D preparations, granulomatous diseases and lymphoproliferative malignancies. In vitamin D toxicity, the clinical courses vary depending on the vitamin D preparation responsible for the hypercalcemia. Hypercalcemia state continues for several months when D2 or D3 are responsible for the toxicity whereas the hypercalcemia would subside in a week when 1 alpha(OH) D3 or 1,25 (OH)2D3 are responsible for the toxicity. Abnormal calcium metabolism can be treated by hydration and glucocorticoids. Hypercalcemia is associated with variety kinds of granulomatous diseases, including sarcoidosis and tuberculosis. The granulomatous tissue is believed to be the site of the ectopic production of 1,25(OH)2D3 in which the regulation of the synthesis is quite different from that in the normal kidney. Glucocorticoid markedly diminishes the synthesis. Hypercalcemia associated with elevated serum 1.25(OH)2D3 levels is also found in patients with lymphomas and some other malignancies. However, there still are not sufficient evidences to prove that the excessive amount of endogenous 1.25(OH)2D3 is the primary cause of the hypercalcemia.

24,25-Dihydroxyvitamin D 3