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Carlos R Ferreira Dillon Kavanagh Ralf Oheim Kristin Zimmerman Julian Stürznickel Xiaofeng Li Paul Stabach R Luke Rettig Logan Calderone Colin MacKichan Aaron Wang Hunter A Hutchinson Tracy Nelson Steven M Tommasini Simon von Kroge Imke AK Fiedler Ethan R Lester Gilbert W Moeckel Björn Busse Thorsten Schinke Thomas O Carpenter Michael A Levine Mark C Horowitz Demetrios T Braddock 《Journal of bone and mineral research》2021,36(5):942-955
Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
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Postequatorial (12 mm) recession of all four horizontal recti was done in nine patients with congenital nystagmus. Fifteen of 18 eyes showed decreased amplitude of nystagmus while 12 eyes also showed an increase in visual acuity. Functionally, significant limitation of ocular motility was not encountered despite unconventionally large recessions. 相似文献
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Shrivastava SK Sharma HP Sinha SK Prasad KM 《Indian journal of pathology & microbiology》1999,42(2):169-170
We report a rare case of Retroperitonial teratoma containing Axial Skeleton long bone. Jaw, pelvis & scapula in a 27 yrs old male. Aberration in monozygotic twinning may rarely present as Fetus in Fetu. Rarer is presentation in Adult. 相似文献
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Prasad PV 《Indian journal of dermatology, venereology and leprology》1996,62(1):16-18
Fifty male patients diagnosed to have superficial pustular folliculitis (SPF) were included in an open trial to study the effects of rifampicin vs dapsone. Rifampicin, in a dose of 10mg/kg body weight for a period of 8 weeks was given for 25 patients in phase I and the drug cleared the lesions in 72%. Dapsone in a dose of 100 mg/day produced moderate response in 20% only. 17 patients who did not clear with dapsone were started on rifampicin (phase II) and 7/17 showed marked improvement. Remissions with rifampicin ranged from 3-9 months or longer. In patients who relapsed, a second course of the drug was effective. 相似文献
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Prasad Kari William R. McConnell Joe M. Finkel Donald L. Hill 《Cancer chemotherapy and pharmacology》1980,4(4):243-248
Summary As determined by a colorimetric assay measuring parent compounds plus ether-extractable, nitroso-containing metabolites, N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) disappeared more rapidly than N-(2-chloroethyl)-N cyclohexyl-N-nitrosourea (CCNU) and N-(2-chloroethyl)-N-(4-transmethylcyclohexyl)-N-nitrosourea (MeCCNU) and their products from the tissues of mice injected IV. Assay of selected samples by high-pressure liquid chromatography revealed that the colorimetric assay for BCNU was specific in that the two assays gave equivalent results. Following IV-injections of CCNU and MeCCNU, however, levels of the parent compounds decreased much more rapidly than the total, color-producing material.Of seven tissues, the largest Cxt values for BCNU, as determined by the colorimetric assay, were noted for blood (442 g-min/ml) and large intestine (285 g-min/g). Liver (29 g-min/g) had the lowest Cxt value, reflecting rapid metabolism of the compound by this organ. Color-producing material related to CCNU disappeared from the solid tissues of mice in a manner generally parallel to that for blood. Of the Cxt values for this compound and its products, those for lung (1753 g-equivalents-min/g), kidney (1633 g-equivalents-min/g), and small intestine (1557 g-equivalents-min/g) were highest. Consistent with its slower rate of metabolism, MeCCNU and its color-producing metabolites remained in most tissues of mice for 12 h following injection. Except for brain (1434 g-equivalents-min/g), Cxt values for this nitrosourea and its metabolites in tissues were higher than those of blood (5485 g-equivalents-min/ml), with kidney (15,324 g-equivalents-min/g), liver (12,921 g-equivalents-min/g), and large intestine (11,501 g-equivalents-min/g) being highest. For each nitrosourea, a fair correlation was observed between the Cxt values for tissues and the toxic and/or antitumor effects at those sites. 相似文献