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Santee, CA, United States

Caron P.,Center Hospitalier University Larrey | Simonds W.F.,U.S. National Institutes of Health | Maiza J.-C.,Center Hospitalier University Larrey | Rubin M.,Columbia University | And 5 more authors.
Clinical Endocrinology | Year: 2011

Objective Some patients with parathyroid carcinoma present with an over-production of nontruncated amino-terminal (NT-N) parathyroid hormone (PTH), a post-transcriptionally modified form of PTH(1-84). This is usually picked up on an elevated whole (W) PTH (third-generation)/total (T) (second-generation) PTH assay ratio (N > 0·8). Patients and design Two parathyroid cancer patients with several episodes of hypercalcaemia and multiple surgeries are described. In both patients, W-PTH, T-PTH and circulating PTH molecular forms separated by high-pressure liquid chromatography (HPLC) were measured with the same assays. qPCR was used to study HRPT2 gene mutation. Results The first patient had total calcium of 3·8 and 3·22 mmol/l before the fourth and fifth surgeries, and third/second-generation PTH ratios of 2·95 and 3·6, respectively. After the fourth surgery, the ratio remained normal for 1 year and increased progressively to 3·6 over 15 months. This preceded hypercalcaemia by 6 months. The ratio became normal after the fifth surgery. HPLC analysis disclosed an over-expression of NT-N PTH to 82·2% (N < 10%) relative to hPTH(1-84) before the fifth surgery. A deletion of all the tested exons of the HRPT2 gene was identified. In the second patient, W-PTH/T-PTH ratio was 0·89 when serum calcium was 3·3 mmol/l. NT-N PTH was also over-expressed at 51·9%. An inactivating mutation of the HRPT2 gene was also identified. Conclusions This may suggest that a progressive rise in third/second-generation ratio may have possible clinical utility to monitor parathyroid cancer recurrence. A possible association between NT-N PTH overproduction and HRPT2 gene inactivation is also suggested. © 2011 Blackwell Publishing Ltd. Source


Malluche H.H.,University of Kentucky | Davenport D.L.,University of Kentucky | Canto T.,Scantibodies Laboratory Inc. | Monier-Faugere M.-C.,University of Kentucky
Clinical Journal of the American Society of Nephrology | Year: 2014

Background and objectives Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss. Design, setting, participants, & measurements This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMDat baseline and changes over 1 year.Multivariable regression was performed to adjust for age, sex, body mass index, and race. Results Eighty-one patients completed the study (mean age=52.6±12.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by eithermethod, 33.3%of the patientswere osteoporotic. Baseline BMDcorrelatedwith sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor.At 1 year, hipQCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). ftermultivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT. Conclusions QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis © 2014 by the American Society of Nephrology. Source


Malluche H.H.,University of Kentucky | Blomquist G.,University of Kentucky | Monier-Faugere M.-C.,University of Kentucky | Cantor T.L.,Scantibodies Laboratory Inc. | Davenport D.L.,University of Kentucky
Journal of the American Society of Nephrology | Year: 2015

Coronary artery calcifications (CACs) are observed in most patients with CKD on dialysis (CKD-5D). CACs frequently progress and are associated with increased risk for cardiovascular events, the major cause of death in these patients. A link between bone and vascular calcification has been shown. This prospective study was designed to identify noninvasive tests for predicting CAC progression, including measurements of bone mineral density (BMD) and novel bone markers in adult patients with CKD-5D. At baseline and after 1 year, patients underwent routine blood tests and measurement of CAC, BMD, and novel serum bonemarkers. A total of 213 patients received baselinemeasurements, of whom about 80% had measurable CAC and almost 50% had CAC Agatston scores.400, conferring high risk for cardiovascular events. Independent positive predictors of baseline CAC included coronary artery disease, diabetes, dialysis vintage, fibroblast growth factor-23 concentration, and age, whereas BMD of the spine measured by quantitative computed tomography was an inverse predictor. Hypertension, HDL level, and smoking were not baseline predictors in these patients. Three quarters of 122 patients completing the study had CAC increases at 1 year. Independent risk factors for CAC progression were age, baseline total or whole parathyroid hormone level greater than nine times the normal value, and osteoporosis by t scores. Our results confirm a role for bone in CKD-associated CAC prevalence and progression. Copyright © 2015 by the American Society of Nephrology. Source


Trademark
Scantibodies Laboratory Inc. | Date: 2012-07-27

Biochemical preparations for the treatment of infections; therapeutic agents for the treatment of infections; biological therapeutic preparations for the treatment of infections; biochemical preparations, namely, monoclonal and/or polyclonal antibodies for the treatment of infections.


Trademark
Scantibodies Laboratory Inc. | Date: 2008-12-15

Biochemical preparations for the treatment of infections; therapeutic agents for the treatment of infections; biological therapeutic preparations for the treatment of infections; biochemical preparations, namely, monoclonal and/or polyclonal antibodies for the treatment of infections.

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