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Biomedical subjects

R Freaney

Publications and source records attributed to R Freaney.

At least 37 records · Page 2Linked to original sources

Secondary hyperparathyroidism in elderly people: combined effect of renal insufficiency and vitamin D deficiency.

The relative effects of renal insufficiency and vitamin D deficiency on parathyroid gland function were assessed in 29 free-living elderly subjects by using a sensitive assay for intact parathyroid hormone (PTH). Serum calcium, phosphate, alkaline phosphatase, creatinine, 25-hydroxyvitamin D [25(OH)D], and PTH were measured after an overnight fast during wintertime, after oral vitamin D therapy (20 micrograms cholecalciferol/d for 4 wk), and at the end of the subsequent summer. Hypovitaminosis D [serum 25(OH)D < 25 nmol/L] was evident in 86% of the subjects during wintertime and 52% had elevated PTH concentrations. Multiple-regression analysis identified serum creatinine as the strongest predictor variable for serum PTH (multiple r = 0.73, P < 0.001). Mean (+/- SD) serum PTH declined from 6.3 +/- 2.8 to 5.0 +/- 2.0 pmol/L (P < 0.001) by the end of the summer season, coincident with an increase in serum 25(OH)D). Secondary hyperparathyroidism is common in elderly people, and in Ireland is the result of both renal insufficiency and hypovitaminosis D.

Aged↗

Parathyroid crisis and acute viral hepatitis B infection.

The simultaneous development of acute hyperparathyroidism and viral hepatitis B infection in a 72 year old male is described. Resolution of the hepatitis was accompanied by improvement in the parathyroid hormone mediated hypercalcaemia. It is postulated that antibodies to the hepatitis B virus may have altered the calcium 'set point' allowing uncontrolled synthesis and release of parathyroid hormone during the acute illness.

Acute Disease↗

Dependence of measured ionized calcium on protein concentration as measured by three ion-selective electrodes.

A positive effect of protein on the measurement of ionized calcium in serum by ion-selective electrodes (ISEs) has been previously reported and the present study confirms this finding. Ionized calcium in serum was measured in the presence of increasing protein concentrations induced by venous stasis in 17 healthy volunteer subjects. Ionized calcium was measured using two commercial analysers, a Radiometer ICA2 analyser and a Baker Analyte+2 analyser, and a calcium cell devised by Covington for the calcium reference method (CRM). Both commercial analysers used charged ionophores and the CRM used a neutral carrier ionophore in the selective membrane. A small but significant rise in ionized calcium with increasing protein was measured on all analysers. Substitution of isotonic KCl for saturated KCl in the reference electrode of the CRM resulted in significantly reduced values for ionized calcium in paired serum samples when measured using the isotonic salt bridge. This study supports the premise that the positive effect of protein is related to the salt bridge concentration of the reference electrode rather than the ISE membrane composition.

Adult↗

Hypercalciuria in parathyroid disorders: effect of dietary sodium control.

Moderate dietary Na restriction (80 mmol/d for 7 days) during constant Ca intake can reduce high urinary Ca excretion to normal levels in idiopathic hypercalciuria (IH). A similar protocol was used to test its effect in primary hyperparathyroidism (PHPT) and also in hypoparathyroid subjects (HOPT) during treatment with dihydrotachysterol (DHT). Nine subjects with PHPT, 10 with HOPT, and one with pseudo-HOPT were evaluated after Na-restricted (80 mmol/d) and Na-supplemented (200 mmol/d) diets for 7 days each with dietary Ca constant. Na restriction resulted in a decrease in mean urinary 24-hour Ca excretion in PHPT subjects (10.6 v 7.6 mmol/d [424 v 304 mg], P less than 0.0001) and in one pseudo-HOPT subject, similar to the pattern seen previously in IH subjects. In contrast, Na restriction was not accompanied by significant change in Ca excretion in HOPT. There was no change in serum immunoreactive PTH (iPTH) or 1,25(OH)2 vitamin D levels in either group when Na intake was altered. Thus, the presence of parathyroid hormone (PTH) is necessary for sodium-related alterations in urinary Ca to occur. The effect of PTH appears to be "permissive" rather than "active." Dietary Na restriction may have a role in the management of hypercalciuria in mild PHPT cases when parathyroidectomy is contraindicated.

Calcitriol↗

Determination of ionised calcium by ion selective electrode is not independent of albumin concentration.

The relationship of ionised calcium measurement to changes in serum total protein and albumin were studied both in vivo and in vitro. During venostasis serum ionised calcium was determined in 10 control subjects using an Orion SS20 analyser. A slight but significant increase in ionised calcium occurred only after prolonged venostasis (15 min), when gross changes in total protein and albumin were seen. The effect of albumin concentration on serum ionised calcium was studied in vitro by the dialysis technique of Payne. The increase in ionised calcium in 40 sera was 0.0198 mmol/l per 10 g albumin change. We conclude that albumin-related variation in serum ionised calcium determination required such gross changes that correction is rarely necessary in clinical practice. When gross albumin alteration occurs, the appropriate correction for the analyser used should be determined and applied.

Adult↗

Hypovitaminosis D and elevated serum alkaline phosphatase in elderly Irish people.

The vitamin D status of 181 elderly Irish community-dwelling and institutionalized subjects was studied during Winter-Spring. The mean serum 25-hydroxyvitamin D level was 10 nmol/L (95% range less than 5.0-59 nmol/L); values were below 25 nmol/L in 79 percent of subjects. A significant seasonal variation of serum 25-hydroxyvitamin D levels was noted in elderly community-dwelling subjects. The previously documented age-related increase in serum alkaline phosphatase activity was significantly less in vitamin D replete subjects than in vitamin D deplete subjects in this study (P less than 0.005). The higher serum alkaline phosphatase values found in the vitamin D deplete subjects may represent mild secondary hyperparathyroidism or osteomalacia. The relationship of vitamin D status to both dietary intake and effective sunlight (latitude) is examined.

Aged↗

Hypovitaminosis D and response to supplementation in older patients with cystic fibrosis.

This study reports serum 25-hydroxy vitamin D (25-(OH)D) levels, bone mineral content and bone maturation in 20 adolescent and adult patients with cystic fibrosis, and their response to the internationally recommended dose of supplementary vitamin D (800 iu/day; 20 micrograms/day). Serum 25-(OH)D values were below normal in 75 per cent of patients and serum alkaline phosphatase values, corrected for age, were increased in 60 per cent. Bone mineral content, measured by photon beam absorptiometry, was below the normal range in 45 per cent of patients and bone age retarded in 45 per cent. Following supplementation with vitamin D 40 per cent of patients failed to achieve normal serum 25-(OH)D levels. We concluded that hypovitaminosis D occurs frequently in older patients with cystic fibrosis and is accompanied by osteopenia and retarded bone maturation.

Adolescent↗

Osteomalacia and osteoporosis: evaluation of a diagnostic index.

Data from a retrospective study in 41 patients is used to suggest an index of bone disease. This is designed as a means of collating available results, clarifying the significance of each in diagnosing either osteomalacia or osteoporosis, and reducing the significance of a single abnormal finding--for example, a raised alkaline phosphatase activity or low serum 25 hydroxy vitamin D, when the overall index score is low. Index scores above 35% would be diagnostic of osteomalacia; scores below 15% if associated with collapsed vertebrae suggest osteoporosis. Scores between 15% and 35% would indicate the need for a bone biopsy to discriminate between osteoporosis and osteomalacia.

Adolescent↗

Importance of dietary sodium in the hypercalciuria syndrome.

Daily urinary calcium excretion in renal stone-forming subjects is shown to vary directly with moderate changes in dietary sodium intake. The changes produced are sufficient to alter the basic diagnostic classification from 'hypercalciuric' to 'normocalciuric' because dietary sodium is reduced from 200 to 80 mM/day. Similar changes were observed in fasting morning 'spot' urine samples, resulting in alteration of diagnostic subclassification between so-called 'absorptive' and 'renal' categories, in the absence of demonstrable change in parathyroid function. Diagnostic and therapeutic studies in stone-forming subjects require control of both dietary calcium and dietary sodium if misinterpretations are to be avoided. Habitual high sodium intake may be an etiological factor in the generation of excessive excretion of calcium, sodium, and phosphate--the hypercalciuria syndrome.

Calcium↗

The pathogenesis of idiopathic hypercalciuria: evidence for renal tubular calcium leak.

A standard oral calcium loading test has been employed in a group of idiopathic hypercalciuria (IH) subjects and in a group of marginally hypercalcaemic subjects with primary hyperparathyroidism (PHPT) in whom the diagnosis was revealed by careful combined measurements of serum ionized calcium and immuno-reactive parathyroid hormone (iPTH). Initial values for serum ionized calcium and creatinine clearance were similar in IH and in a control group of normal subjects, whereas iPTH levels were normal or low. Following oral loading, serum ionized calcium rose to similar levels in both IH and control subjects, with no suggestion of relative hypercalcaemia due to a postulated intestinal hyperabsorption in the IH group. A renal tubular calcium 'leak' was however clearly evident in the IH group, in both the fasting and post-absorptive phase. In the marginally hypercalcaemic PHPT subjects on the other hand, a relative post-absorptive hypercalcaemia was clearly apparent, as well as a gross renal tubular calcium leakage. Thus careful preliminary separation of masked PHPT from IH subjects is an essential step before evaluation of response to oral calcium challenge in stone-forming subjects. When this is done, no evidence of a relative post-absorptive hypercalcaemia can be seen in the residual IH group, and hypercalciuria appears to be 'renal' rather than 'absorptive' in origin.

Calcium↗