Mineral and bone disorders including osteoporosis are common in dialysis patients and contribute to increased morbimortality. However, whether denosumab and alendronate are effective and safe treatments in hemodialysis patients is not known. Thus, we conducted a prospective, three-center study of 48 hemodialysis patients who were diagnosed as having osteoporosis and had not received anti-osteoporotic agents previously. Participants were randomized to either denosumab or intravenous alendronate, and all subjects received elemental calcium and calcitriol during the initial 2 weeks. The primary endpoint was the percent change in lumbar spine bone mineral density (LSBMD) at 12 months of treatment. The secondary endpoints included the following: change in BMD at other sites; change of serum bone turnover markers (BTM), coronary artery calcium score (CACS), ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), flow mediated dilation (FMD), and intima-media thickness at the carotid artery (CA-IMT); change from day 0 to day 14 in serum levels of Ca and P; time course of serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (i-PTH); new fractures; and adverse events. Initial supplementation with elemental calcium and calcitriol markedly ameliorated the decrease of serum corrected calcium (cCa) levels induced by denosumab during the first 2 weeks, whereas serum cCa levels in the alendronate group were increased. Denosumab and alendronate markedly decreased serum levels of BTM and increased LSBMD at 12 months compared with baseline. However, no significant differences were found in the changes in LSBMD between the two groups. The serum cCa, P, and i-PTH levels in the two groups were maintained within the appropriate range. In contrast to the anti-osteoporotic effects, no significant differences after 12 months of treatment were found in the CACS, CA-IMT, ABI, baPWV, and FMD compared with pretreatment in both groups. Denosumab and alendronate treatment improved LSBMD, reduced BTM, and appeared to be safe in hemodialysis patients with osteoporosis. Ca ¼ calcium; P ¼ phosphate; ALP ¼ alkaline phosphatase; PTH ¼ parathyroid hormone; TRACP-5b ¼ tartrate-resistant acid phosphatase 5b; t-PINP ¼ total-type I collagen N-terminal propeptide; BAP ¼ bone-specific ALP; Hs-CRP ¼ high-sensitivity C-reactive protein; CACS ¼ coronary artery calcium score; CA-IMT ¼ intima-media thickness at the carotid artery; ABI ¼ ankle brachial pressure index; baPWV ¼ brachial-ankle pulse wave velocity; FMD ¼ flow mediated dilation.Data are presented as mean AE SD (range from 25th to75th percentile) or n (%). Journal of Bone and Mineral ResearchEFFECTS OF ANTI-OSTEOPOROTIC AGENTS IN HEMODIALYSIS PATIENTS 5 ISERI ET AL.
A Raman spectroscopic study on property changes of water in the course of a temperatureresponsive solution-aggregate transition phenomenon of aqueous poly(N-isopropylacrylamide) and poly[N-(3-ethoxypropyl)acrylamide] solutions was carried out. Upon the transition of polymers from coil to globule followed by the aggregation of individual polymer chains, the height ratio of the peaks at 3250 and 3400 cm-', corresponding to the 0-H stretching of water molecules, was drastically changed. Contribution of small water domains included in polymer aggregates (so-called interstitial water) to the change in the Raman spectra was suggested. Effects of polymer concentration and molecular weight of polymers on the spectra were also examined.
Membranous nephropathy (MN) caused by disease-modifying antirheumatic drugs is relatively common in patients with rheumatoid arthritis (RA). However, MN rarely occurs due to RA itself. We describe a 61-year-old woman with RA who showed nephrotic syndrome. She was admitted because of systemic edema and severe arthritis. She had a long history of RA successfully treated with methotrexate (MTX), but discontinued all treatments 4 years before hospitalization. She had never been treated with bucillamine or gold. Laboratory test results were positive for anti-cyclic citrullinated peptide antibody and negative for anti-nuclear antibody. Renal pathologic findings were compatible with MN. Immunofluorescence microscopy showed IgG, IgA, κ, λ, and C3 along the glomerular capillary wall, whereas deposition of IgM or C1q was not detected. In terms of the IgG subclasses, only IgG2 findings were positive. Results for glomerular antigen and serum antibody for M-type phospholipase A2 receptor and thrombospondin type 1 domain-containing 7A were negative. HLA type did not include the HLA-DQA1 gene that is a concern in primary MN (PMN). She responded to intensive immunosuppressive therapy consisting of prednisolone, tacrolimus, and MTX with a parallel reduction of proteinuria. Based on assessments for differentiating PMN from secondary MN (SMN), the diagnosis of the present case was incompatible with PMN. Taken together, we consider that SMN in the present case was due to RA itself rather than drug-induced MN.
The integrated circuits with low driving voltages have been widely used in high-efficiency power equipments, information communication equipments, medical equipments so on. However these equipments are very liable to be weak when surges occur as lightning surges, switching surges and/or static discharges. The overvoltages generated from the surge will affect power apparatus and electric appliances, which make of deterioration. Moreover the overvoltages occur frequently in power switching devices or lightning phenomena as multi strokes. Therefore AC phase controlled testing apparatus superimposed with high voltage double pulses has been developed in order to investigate effects of overvoltages to insulating materials and surge protection devices. The developed device will control the double pulses at any phase angle with phase control circuits consisting of RC integrated circuits controlled by the triggering circuit of zero-cross AC power source. This paper describes a developed AC phase controlled testing apparatus superimposed with double pulses and small gap breakdown characteristics as one of its applications.
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