Biomedical subjects
Paul Glendenning
Publications and source records attributed to Paul Glendenning.
Standardised, metabolite-specific assays with validated decision limits: utopian ideal or achievable goal?
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8: Disorders of bone and mineral other than osteoporosis.
Rickets in children and osteomalacia in adults are caused by undermineralisation of bone, which increases its susceptibility to bending and fracture; treatment is with calcium, vitamin D or phosphate, depending on the specific mineral or vitamin deficiency. In Paget's disease, osteoclasts are overactive and produce woven or "repair" bone, which is mechanically weaker than lamellar bone; treatment is with antiresorptive bisphosphonate drugs. Cancers can produce bone lysis through direct spread within the skeleton or production of endocrine parathyroid hormone-like factors; treatment is with a bisphosphonate, plus appropriate therapy for the cancer. Cancer can also produce hypercalcaemia if the capacity of the kidneys to excrete the calcium dissolved from bone is exceeded; treatment is with saline infusion to increase excretion and a bisphosphonate. Primary hyperparathyroidism is the other common cause of hypercalcaemia and is usually associated with a single parathyroid adenoma; it is best treated with parathyroidectomy. Hypocalcaemia may result from severe decrease in calcium absorbed or lack of parathyroid action; both are treated with calcium and vitamin D (ergocalciferol or calcitriol). These disorders range from nutritional deficiencies to complex genetic and metabolic diseases
Estrogen and androgen regulation of plasma membrane calcium pump activity in immortalized distal tubule kidney cells.
The ATP dependent plasma membrane calcium pump (PMCA) is a regulator of renal calcium reabsorption. The effect of estrogen and dihydrotestosterone to increase the activity of the PMCA in membrane vesicle preparations from a distal tubule cell line was investigated. 17beta Estradiol (10(-10)M) increased PMCA activity (1.5 +/- 0.2-fold increase compared to control) with 24 h, but not 1 or 5 h, of exposure, an effect that was blocked by the addition of the estrogen antagonist ICI 164384. alpha Estradiol did not increase PMCA activity. Dihydrotestosterone (10(-11)M ) resulted in a dose dependent increase in PMCA activity (1.5+/-0.1-fold increase compared to control) with 24h, but not 1 or 5h, of exposure, an effect that was blocked by the androgen receptor agonist flutamide. Testosterone (10(-5)M) also increased PMCA activity (1.9+/-0.3-fold increase compared to control). Neither estrogen nor dihydrotestosterone increased PMCA protein expression in MDBK cells, indicating that these hormones increase PMCA activity by regulating PMCA activity rather than PMCA expression. These results demonstrate receptor dependent stimulatory effects of both estrogen and dihydrotestosterone to increase PMCA activity. and have significance for our understanding of estrogen and androgen deficient states on calcium transport.
Issues of standardization and assay-specific clinical decision limits for the measurement of 25-hydroxyvitamin D.
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Issues of methodology, standardization and metabolite recognition for 25-hydroxyvitamin D when comparing the DiaSorin radioimmunoassay and the Nichols Advantage automated chemiluminescence protein-binding assay in hip fracture cases.
BACKGROUND: Deficiency of vitamin D is commonly associated with hip fracture and treatment with vitamin D reduces hip fracture rates. Consequently, the demand for assays to measure 25-hydroxyvitamin D (25-OHD) has increased. The Nichols Advantage chemiluminescence protein-binding assay (CLPBA) for 25-OHD is a first-generation automated immunoassay with decreased turnaround time, reduced manual handling and non-radioactive label. METHODS: We compared the CLPBA to the DiaSorin radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC) for the measurement of 25-OHD using 161 samples from hip fracture patients and samples before and after institution of ergocalciferol (vitamin D(2)) therapy. RESULTS: A negative bias for the CLPBA at concentrations below 30 nmol/L and a positive bias at 25-OHD values above 30 nmol/L compared with the RIA resulted in diagnostic discordance for one in three samples when using 30 and 50 nmol/L as decision limits. HPLC analysis confirmed the presence of a negative bias for the CLPBA at low values. Both immunoassays under-estimate 25-hydroxyvitamin D(2). CONCLUSIONS: The discordance between 25-OHD values may be due to differences in standardization of each assay relative to HPLC. Our results emphasize the need for assay-specific clinical decision limits.
Low rate of compliance with ergocalciferol therapy in vitamin-D-deficient patients with hip fracture.
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The estimated prevalence of familial hypocalciuric hypercalcemia (FHH).
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Vitamin D deficiency and multicultural Australia.
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Surgically correctable hypertension.
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Vitamin D status and redefining serum PTH reference range in the elderly.
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Preanalytical factors in the measurement of intact parathyroid hormone with the DPC IMMULITE assay.
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Parathyroid hormone is more stable in EDTA plasma than in serum.
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