[Primary hyperparathyroidism].
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Calcium↗
Biomedical subjects
Masaaki Inaba
Publications and source records attributed to Masaaki Inaba.
[significance of PTH (1-84) assay in the management of chronic renal failure and the current status and future of the treatment of renal osteopathy].
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Chronic Kidney Disease-Mineral and Bone Disorder↗
Insulin resistance index as a predictor for pioglitazone treatment in type 2 diabetes.
BACKGROUND: It is difficult to predict the hypoglycemic effect of pioglitazone (a thiazolidinedione) as an insulin sensitizer. The purpose of the present study was to investigate whether insulin resistance index, homeostasis model assessment index (HOMA-IR) is a useful predictor of hypoglycemic effect of pioglitazone in comparison with body mass index (BMI). METHODS: Thirty-four type 2 diabetic patients (14 men and 20 women, mean age 60 +/- 14 years) were treated with pioglitazone, 15 mg per day for 3 months. Eighteen subjects showed a decrease of 0.5% or more in HbA1C after treatment and were considered responders while 16 subjects were non-responders. A receiver operating characteristic (ROC) analysis was performed to determine HOMA-IR and BMI sensitivity and the false positive rate (1-specificity) for discriminating responders from non-responders. RESULTS: Although there was no significant difference in age, sex, fasting plasma glucose, HbA1C and BMI between responders and non-responders, fasting insulin levels and HOMA-IR prior to treatment were significantly higher in the responders than in the non-responders. In ROC analysis, the sensitivity, false positive rate, and efficiency for HOMA-IR at the cut-off value, 4.6, with the highest efficiency were 81.2%, 22.2%, and 79.4%, respectively, and those for BMI at the cut-off value, 29.1, were 87.5%, 53.3%, and 67.7%, respectively. CONCLUSION: HOMA-IR is a useful predictor of pioglitazone treatment in type 2 diabetic patients.
Aged↗
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↗
Disease associations and altered immune function in CD45 138G variant carriers.
The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance.
Alternative Splicing↗
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↗
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↗
Significance of intima-media thickness in femoral artery in the determination of calcaneus osteo-sono index but not of lumbar spine bone mass in healthy Japanese people.
The aim of this cross-sectional study was to investigate whether physical activity and local arterial thickening may affect bone metabolism. To analyze the effects of physical activity and atherosclerosis on bone in healthy Japanese people, health-related quality of life (HRQL) and local arterial thickening were assessed by means of the Medical( )Outcomes Study 36-item Short Form (SF-36), and intimal-medial thickness (IMT) in common carotid artery (CA) and femoral artery (FA), respectively. Bone mineral density (BMD) in lumbar spine was measured by dual X-ray absorptiometry and the osteo-sono assessment index (OSI) of the calcaneus by ultrasound. Healthy subjects (106 male and 154 female) were recruited from those who participated in a local health check program at the Osaka City University Hospital. A significant correlation existed between lumbar spine BMD and calcaneus OSI (r=0.551, P<0.0001). Among various scores in SF-36, only physical functioning score correlated weakly but significantly in a positive manner with lumbar spine BMD (rho=0.156, P=0.0147) and calcaneus OSI (rho=0.190, P=0.0024). Lumbar spine BMD correlated negatively with FA IMT (rho=-0.191, P=0.0027) whereas calcaneus OSI with FA IMT (rho=-0.199, P=0.0014). Multiple regression analyses revealed a significant association between FA IMT and calcaneus OSI, whereas lumbar spine BMD did not correlate significantly with FA or CA IMT. When subjects were restricted to female, FA IMT, but not CA IMT, still showed tendency against independent factors negatively associated with calcaneus OSI. Furthermore, lumbar spine BMD, but not calcaneus OSI, was weakly but significantly associated with increased physical functioning score independently. In conclusion, it was suggested that physical activity may affect bone strength in lumbar spine and calcaneus and that FA IMT might be a significant determinant of bone strength in calcaneus, but not in lumbar spine, in healthy Japanese subjects.
Arteriosclerosis↗
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↗
A multicenter phase II study of docetaxel 60 mg/m2 as first-line chemotherapy in patients with advanced or recurrent breast cancer.
PURPOSE: Docetaxel is an active agent as first-line chemotherapy in patients with advanced breast cancer at a dosage of 100 mg/m2. However, the efficacy of this agent as a first-line drug when used at a lower dosage is unclear. This study was performed to evaluate the clinical efficacy and safety of 60 mg/m2 docetaxel for the treatment of breast cancer. PATIENTS AND METHODS: This study enrolled 23 patients with advanced and/or metastatic breast cancer, who had not been treated with an anthracycline or taxane previously. Treatment with docetaxel was continued in patients showing a response until there was evidence of disease progression or unacceptable toxicity. RESULTS: Among 20 fully evaluated patients, the overall response rate was 50.0% and the median time to progression was 31 weeks. The most commonly observed adverse events were neutropenia (78.2%) and fatigue (60.9%). Fluid retention occurred in only 8.7% of the patients. Adverse events did not cause discontinuation of the treatment. CONCLUSION: Docetaxel achieved good disease control with mild adverse events in first-line treatment at a dosage of 60 mg/m2.
Adult↗
Tumor-forming idiopathic retroperitoneal fibrosis: report of a case.
Idiopathic retroperitoneal fibrosis (IRF) is characterized by the progressive proliferation of connective tissue, but it rarely results in the formation of a mass. Herein, we report a rare case of tumor-forming IRF. A 76-year-old woman was referred to our hospital after a tumor in the right retroperitoneum was found by ultrasonography and computed tomography. Magnetic resonance imaging showed a 5 x 8 x 5-cm irregularly shaped tumor, lying adjacent to the right kidney, with a high-intensity T1-weighted image and a high-intensity T2-weighted image. Hormonal levels were within normal limits. Surgery was performed because of the possibility of an adrenal cancer. The tumor was firm, measured 7 x 8 x 4 cm, and weighed 115 g. The pathological diagnosis was retroperitoneal fibrosis. It is very difficult to distinguish tumor-forming IRF from malignancy. Several examinations, including needle aspiration cytology and biopsy, are necessary for the diagnosis and treatment of this disease.
Adrenal Gland Neoplasms↗
Telomerase activation and expression of its catalytic subunits in benign and malignant tumors of the parathyroid.
PURPOSE: Telomerase activity (TA) has been extensively studied in tumors of many organs, but not the parathyroid gland. Therefore, we investigated TA in parathyroid tumors, and examined the mRNA expression of its catalytic subunits. METHODS: We examined 17 single adenomas, one hyperplastic parathyroid gland, and one metastatic parathyroid cancer and quantified TA by fluorescence-based TRAP analysis. We also studied the expression of telomerase catalytic subunits in nine adenomas and one cancer by reverse transcription - polymerase chain reaction (RT-PCR) analysis. RESULTS: Telomerase activity was not detected in any of the adenomas or the hyperplastic gland; however, the metastatic cancer was highly positive for TA. Both human telomerase RNA ( hTR) and human telomerase-associated pretein (hTEP-1) mRNA were detected universally in every specimen tested. Conversely, human telomerase reverse transcriptase (hTERT) mRNA was not detected by the conventional electrophoresis-based technique. Faint expression of hTERT mRNA was detected by real-time RT-PCR only in the sample of parathyroid cancer. DISCUSSION: We hypothesize that TA plays a role in the malignant transformation of parathyroid disease and suggest that hTERT mRNA expression could be the key step for TA as in other malignancies. Telomerase activity and hTERT may be useful molecular targets of parathyroid cancer.
Adenoma↗
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↗
Long-term effect of intermittent cyclical etidronate on microarchitecture and quality of trabecular bone in an elderly woman with severe osteoporosis.
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Aged↗
Secondary osteoporosis: thyrotoxicosis, rheumatoid arthritis, and diabetes mellitus.
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Animals↗
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↗
Short-term aerobic exercise improves arterial stiffness in type 2 diabetes.
OBJECTIVE: To investigate whether: (1) aerobic exercise decreases arterial stiffness and (2) reduction in arterial stiffness is associated with improvement in insulin resistance in type 2 diabetes. METHODS: Common carotid and femoral arterial stiffness was ultrasonographically evaluated using stiffness index beta in 23 type 2 diabetic subjects before and after a 3-week exercise protocol including ergometer and walking. Insulin sensitivity (Clamp-IR) was assessed using euglycemic-hyperinsulinemic clamp before and after the protocol. Arterial stiffness was also examined in steady hyperinsulinemic state during clamp. RESULTS: Anthropometrical factors did not change following exercise. Clamp-IR tended to increase after exercise protocol (P = 0.061). Stiffness index beta decreased following exercise in both common carotid and femoral arteries (P = 0.020 and P < 0.001, respectively). DeltaClamp-IR was significantly correlated with the changes in stiffness index beta of both common carotid (P = 0.040) and femoral artery (P = 0.016). Divided into tertiles according to DeltaClamp-IR, decreases in stiffness index beta for both common carotid (P = 0.009) and femoral (P = 0.037) arteries was greater in tertile group with a higher DeltaClamp-IR. Hyperinsulinemia during clamp decreased stiffness index beta in both common carotid (P = 0.031) and femoral (P = 0.025) arteries before exercise, but these effects disappeared after the exercise protocol. CONCLUSIONS: Short-term aerobic exercise significantly decreased arterial stiffness in both common carotid and femoral arteries, and the reduction of stiffness was associated with improvement of insulin resistance in type 2 diabetes.
Adult↗