The measurement of serum alkaline phosphatase in clinical medicine.
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Biomedical subjects
Publications and source records attributed to S Posen.
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Mitochondrial preparations from 4 human kidneys produced 1,25-dihydroxycholecalciferol and 24,25 dihydroxycholecalciferol at rates of 0.019 - 0.114 and 0.029 - 0.164 pmol/mg/min respectively at a 25-hydroxycholecalciferol concentration of 1 mumol per litre. Mitochondria from a fifth kidney failed to produce either metabolite.
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A case of Cushing's disease and hyperprolactinaemia is reported. The two endocrinological abnormalities could be suppressed independently of one another, and both were apparently relieved by transsphenoidal hypophysectomy.
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When ovariectomized mice are treated with estradiol-17 beta, their uterine tissue shows an increase in 25-hydroxycholecalciferol binding protein as well as an increase in estradiol- and progesterone-binding proteins.
Bone biopsies were performed and serum concentrations of vitamin D metabolites were measured in twenty-four patients with chronic renal failure. The concentrations of three metabolites--25-dihydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D (24,25-OH2D) and 1,25-dihydroxyvitamin D (1,25-OH2D)--were significantly lower in uraemic than in normal sera. There was a positive correlation between serum 24,25-OH2D and serum 25-OHD, whereas serum 1,25-OH2D values, which were independent of those of the other vitamin D metabolites, were negatively correlated with serum creatinine and serum inorganic phosphate. The two major skeletal lesions, osteomalacia and parathyroid osteopathy, while coexisting in many patients, varied independently in relation to their severity and were correlated with different vitamin D metabolites. The severity of osteomalacia was negatively correlated with the serum concentrations of 25-OHD and 24,25-OH2D while th severity of parathyroid osteopathy was negatively correlated with serum 1,25-OH2D values. To our knowledge these are the first systematic studies correlating skeletal histology with dihydroxylated vitamin D metabolites in renal failure in man.
A case of central diabetes insipidus is reported in association with idiopathic hypoparathyroidism, adrenal failure and mucocutaneous candidiasis. The diabetes insipidus was recognised at the same time as the discovery of aldosterone and cortisol deficiency, and occurred several years after the initial onset of mucocutaneous candidiasis and hypocalcaemia. Control of the diabetes insipidus was achieved initially with nasal aqueous lysine vasopressin and later with desmopressin. The development of diabetes insipidus may be a further aspect of endocrine secretory failure associated with idiopathic hypoparathyroidism.
Assays of serum immunoreactive parathyroid hormone are clinically useful in the differential diagnosis of hypercalcaemic states and in the assessment of the severity of parathyroid bone disease in uraemic patients. Serum immunoreactive calcitonin measurements are essential in the investigation of individuals who might be suffering from medullary carcinoma, and such measurements may be used in the detection of metastases. Serum 25-hydroxyvitamin D assays are useful in patients receiving pharmacological doses of vitamin D, to monitor patient compliance and to prevent the occurrence of vitamin D intoxication. Low values in patients with renal failure and in patients with malabsorption and highly suggestive of the presence of osteomalacia. The measurement of serum levels of dihydroxylated vitamin D metabolites is currently of doubtful clinical relevance, though such measurements may become useful in monitoring patients receiving these compounds therapeutically.
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Calcitonin in pharmacologic doses influences the renal handling of electrolytes, especially phosphate and sodium. High-affinity receptors exist for calcitonin in the kidney and are probably linked to adenylate cyclase activation. Calcitonin accumulates in the serum in renal failure, and may have a role in modifying the expression of the bone disease of chronic renal failure. In chronic renal failure, calcitonin is present in the serum in multiple molecular forms but the biologic activity of each form is not known. Some immunoreactive calcitonin appears in the urine. The amount appearing in relation to calcitonin secretion rates requires further exploration.
We describe a simplified assay for 24,25-and 1.25-dihydroxyvitamin D in human serum. It involves two preparative steps, and normal chick intestine is used in preparing cytosol-binding protein. Our results for 24,25-dihydroxyvitamin D include a reference interval of 2.9--16 nmol/L (1.2--6.7 microgram/L), a mean of 6.7 nmol/L (2.8 microgram/L), an intra-assay CV of 11%, and an interassay CV of 22%. For 1,25-dihydroxyvitamin D, these data were 29--168 pmol/L (12--70 ng/L), 86 pmol/L (36 ng/L), 12%, and 22%, respectively. In hypoparathyroid patients with vitamin D intoxication, mean concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum were significantly above normal; the 1,25-dihydroxyvitamin D concentrations were significantly below normal. Patients with malabsorption and/or post-gastrectomy states had significantly subnormal values for both 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum, and there was a significantly negative correlation between each of these biochemical values and the severity of osteomalacia. We also discuss cost effectiveness of assaying vitamin D metabolites in human serum.
Assays of serum immunoreactive parathyroid hormone are clinically useful in the differential diagnosis of hypercalcaemic states and in the assessment of the severity of parathyroid bone disease in uraemic patients. Serum immunoreactive calcitonin measurements are essential in the investigation of individuals who might be suffering from medullary carcinoma and may be used in the detection of metastases. Serum 25-hydroxyvitamin D assays should be performed in patients receiving pharmacological doses of vitamin D to monitor patient compliance and to prevent the occurrence of vitamin D intoxication. Low values in patients with renal failure and in patients with malabsorption are highly suggestive of the presence of osteomalacia. The measurement of serum levels of dihydroxylated vitamin D metabolites is currently of doubtful relevance though such measurements may become useful in monitoring patients receiving these compounds therapeutically.
A two-enzyme method is presented for estimating urinary oxalate by continuous-flow analysis. Oxalate is decarboxylated, yielding formate, which is subsequently oxidized in the presence of NAD+, yielding NADH. The NADH, measured colorimetrically, is proportional to the amount of oxalate originally present in the sample. Urine is pretreated by precipitation of the oxalate and extraction of the precipitate in citrate buffer. A correction factor for the extraction efficiency is given by the recovery of [U-14C]oxalic acid added to aliquots of the 24-h urine specimen. The normal range obtained by this method was 0.20 to 0.52 mmol/24h (18 to 47 mg/24h) with a mean value of 0.37 mmol/24 h (33 mg/24h). The between-assay CV was 7.6% (n = 12), within-assay CV 3.2% (N = 25). Unlabeled oxalate (0.5 and 1.0 mol/L) added to 28 urine samples gave a mean analytical recovery of 95% (SD 10%).
A patient with metastatic medullary carcinoma of the thyroid, Cushing's syndrome, and severe diarrhoea is presented. The manifestations of Cushing's syndrome were controlled with a combination of aminogluthethimide and metyrapone. The cause of the diarrhoea has not been found, and it remains resistant to treatment.
Cytosol receptors for 25-hydroxycholecalciferol, oestradiol and progesterone were measured in human mammary carcinomas. Significant positive correlations were found between the concentrations of all three receptors.
In twenty-one patients with chronic hypoparathyroidism a close correlation was observed between the prescribed dose of ergocalciferol and mean serum 25-hydroxycalciferol levels. In the 75 serum specimens examined, a significant correlation was found between 25-hydroxycalciferol levels and calcium concentrations. The measurement of serum 25-hydroxycalciferol levels is of potential clinical value in the prediction of hyper- or hypocalcaemic episodes and in monitoring patient compliance.