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Biomedical subjects

H Heath

Publications and source records attributed to H Heath.

At least 91 records · Page 5Linked to original sources
PubMed1989

Effects of altered calcium intake on diurnal and calcium-stimulated plasma calcitonin in normal women.

We sought to determine if any protective effect of dietary calcium (Ca) or Ca supplements on bone could be at least partially mediated by increased calcitonin (CT) secretion. First we studied 10 healthy premenopausal women (median age, 35.5 years) who were randomized to high or low dietary Ca intake (1752 versus 391 mg elemental Ca per day) for 2 weeks and then crossed over. At the end of each dietary period, blood was drawn on 1 day at 0800, 1200, 1700, and 2000 h to assess diurnal variation of plasma CT levels. CT secretory reserve was assessed on the next day by Ca infusion (2 mg Ca per kg body weight over 5 minutes). Next, we studied 10 healthy premenopausal women who took a low-Ca diet (approximately 400 mg Ca per day) for a 2 week control period. The women were then randomized to high- or low-Ca intake [400 mg dietary Ca +/- 1500 mg Ca per day (as supplemental CaCO3)] and then crossed over. At the end of each study period, the diurnal variation in CT was tested on day 1; the CT secretory reserve was assessed on day 3 by an oral Ca load (500 mg as CaCO3)] and on day 5 by Ca infusion. Plasma immunoreactive CT was measured in whole plasma (iCT) and after silica extraction (exCT), predominantly monomeric CT. Neither increased dietary Ca nor Ca supplements affected the diurnal levels of iCT or exCT or augmented plasma CT responses to an oral Ca load.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Calcium, magnesium, and phosphorus metabolism in dogs given intravenous triacetin.

Previous studies suggested that acetate in parenteral solutions may adversely affect mineral metabolism by causing sequestration of inorganic phosphate and calcium in the liver. In this study, triacetin, a short-chain triglyceride of acetate and a potential parenteral nutrient, was infused for 3 h at an isocaloric rate in mongrel dogs (n = 6) to test its effects on serum phosphorus, calcium, and magnesium metabolism. There was no change in serum P or Ca. The serum Mg concentration decreased from 0.7 +/- 0.03 to 0.57 +/- 0.03 mmol/L (p less than 0.001) by 90 min and remained at this level for the remainder of the study. The triacetin infusion did not influence fractional urinary Mg excretion; thus, the decrease in serum Mg was likely because of an increase in cellular transport of this cation. A short-chain triglyceride administered to dogs at a rate approximating resting energy expenditure has no demonstrable adverse effects on mineral metabolism.

Acetates↗
PubMed1989

Kinetics of erythrocyte plasma membrane (Ca2+, Mg2+)ATPase in familial benign hypercalcemia.

The pathogenesis of familial benign hypercalcemia (FBH) is unknown. Possible explanations for the disorder include a set-point error in parathyroid gland regulation and intrinsic renal hyperreabsorption of calcium. Thus, FBH may involve an alteration in cellular calcium transport, especially in renal and parathyroid cells. A primary mediator of cellular calcium transport is (Ca2+,Mg2+)ATPase. Therefore, we examined in detail the kinetics of (Ca2+,Mg2+)ATPase activity in erythrocyte plasma membranes from 11 patients with FBH from 7 families, 5 patients with untreated primary hyperparathyroidism, and equal numbers of age- and sex-matched normal subjects. (Ca2+,Mg2+)ATPase activity was measured in isolated membranes as a function of free calcium (0.05-300 mumol/L) in the presence or absence of calmodulin (600 nmol/L) and as a function of calmodulin (0-1800 nmol/L). We found no significant differences in calcium- or calmodulin-dependent (Ca2+,Mg2+)ATPase kinetics between patients with FBH or primary hyperparathyroidism and their age- and sex-matched normal subjects. None of the kinetic parameters was correlated with serum calcium or serum PTH values. We postulate that a mechanism other than a global defect in (Ca2+,Mg2+)ATPase activity is responsible for the hypercalcemia in patients with FBH.

Adult↗
PubMed1989

Familial benign (hypocalciuric) hypercalcemia. A troublesome mimic of mild primary hyperparathyroidism.

Familial benign hypercalcemia, or hypocalciuric hypercalcemia, may be defined as a dominantly inherited disorder of calcium and magnesium metabolism, characterized by lifelong hypercalcemia and hypermagnesemia (both of variable degree), that usually is not associated with any symptoms, physical signs, reduced vitality, or ill health. Chondrocalcinosis, pancreatitis, gallstones, and neonatal primary hyperparathyroidism are possible rare associations, but findings differ among various studies. The biochemical findings are bland, with "normal" values for serum PTH by many techniques, modest hypophosphatemia, and other findings usually normal. A low calcium:creatinine clearance ratio is suggestive of, but not diagnostic for, FBH; urinary calcium excretion less than 100 mg per day may be just as helpful. The diagnosis should not be made casually or without family screening, because the findings in a given patient may be identical to those in mild primary hyperparathyroidism. The major rationale for careful evaluation is to diagnose the syndrome of FBH and to help affected family members avoid needless expense and the risk of further evaluation and treatment.

Adult↗
PubMed1989

Therapeutic radiation and hyperparathyroidism. A case-control study in Rochester, Minn.

A case-control study was conducted among residents of Rochester, Minn, to assess the influence of prior therapeutic radiation on the risk of primary hyperparathyroidism. Fifty-one cases of surgically proven primary hyperparathyroidism diagnosed from 1975 through 1983 were each matched by age and gender to two control subjects, with radiation exposure documented through preexisting medical records. The overall odds ratio for any prior therapeutic radiation therapy was 1.9 (95% confidence interval, 0.9 to 4.4) and it was 2.3 (95% confidence interval, 0.9 to 5.7) when limited to those with prior head and neck radiation. Among women, the figures were 2.9 (95% confidence interval, 1.1 to 7.5) for any prior therapeutic radiation and 3.4 (95% confidence interval, 1.2 to 10.2) for head and neck exposure. This study confirms the association between primary hyperparathyroidism and prior therapeutic radiation exposure, at least for women in this population.

Adenoma↗
PubMed1988

Differential effects of parathyroid hormone and its analogues on cytosolic calcium ion and cAMP levels in cultured rat osteoblast-like cells.

While the stimulatory effect of parathyroid hormone (PTH) on osteoblast-like cell adenylate cyclase is well known, the effect of PTH on cytosolic calcium ion ([Ca2+]i) mobilization is controversial, one group finding no effect but others reporting various increases. We investigated the effects on [Ca2+]i of synthetic rat PTH fragment 1-34 (rPTH(1-34)) and two bovine PTH analogues that inhibit PTH's stimulation of adenylate cyclase (bovine 8,18Nle, 34Tyr-PTH(3-34) and 34Tyr-PTH(7-34]. [Ca2+]i was measured before, during, and after exposure to PTH analogues in perifused, attached osteoblast-like rat osteosarcoma cells (ROS 17/2.8) that had been scrape-loaded with the luminescent photoprotein aequorin. Resting [Ca2+]i was 0.094 +/- 0.056 microM (mean +/- S.D., n = 103) and rose in a time- and dose-specific way after exposure to rPTH(1-34). At 10(-10) M rPTH(1-34), [Ca2+]i rose 100% within 30 s to a plateau; higher concentrations of PTH yielded increasing initial peaks of [Ca2+]i followed by lower plateaus. At 10(-6) M, the initial peak was 5-fold basal, or 0.64 +/- 0.07 microM. Both analogues of PTH were at least partial agonists for [Ca2+]i mobilization and did not reduce peak [Ca2+]i when co-perifused with rPTH(1-34). However, the analogues did reduce significantly rPTH(1-34)-induced cAMP accumulation and did not increase cAMP accumulation by themselves. Thus, rPTH(1-34) strongly mobilizes [Ca2+]i in ROS 17/2.8 cells, at near-physiologic concentrations. Failure of the PTH analogues to block the effect of PTH on [Ca2+]i while inhibiting the effect on cAMP accumulation suggests separate pathways for PTH activation of adenylate cyclase and mobilization of calcium.

Adenylyl Cyclases↗
PubMed1988

Acute effects of oral phosphate-salt ingestion on serum phosphorus, serum ionized calcium, and parathyroid hormone in young adults.

We studied the effect of acute oral phosphate loading on parathyroid hormone (PTH) secretion and action. Eighteen adults were studied before and after ingestion of 1 g elemental phosphorus as neutral sodium-potassium phosphate in grape juice or in water and 1.7 g NaCl in juice was used as a control. Five subjects were studied after ingesting 1.5 g P in juice. Blood was drawn every 15 min from -45 to +300 min for measurement of serum ionized calcium (Ca++), P, total Ca, creatinine, and immunoreactive PTH (iPTH); urine was collected hourly. Serum P declined after NaCl ingestion but rose significantly after ingestion of 1 g P in juice or in water. There were no significant changes in serum Ca++, iPTH, or urinary cyclic AMP excretion. Acute ingestion of 1-1.5 g P, which exceeds the P content of a normal meal, does not decrease serum Ca++ or increase iPTH secretion or renal action in normal adults.

Adult↗
PubMed1988

Cosecretion of calcitonin gene products: studies with a C18 cartridge extraction method for human plasma PDN-21 (katacalcin).

PDN-21, the carboxyl-terminal flanking peptide encoded by the calcitonin (CT) gene, has been found in plasma of patients with medullary thyroid carcinoma and reportedly is cosecreted with CT. To test whether PDN-21 and CT are cosecreted in normal subjects, we developed a RIA for PDN-21 and measured immunoreactive CT and PDN-21 in whole plasma and silica or C18 cartridge extracts of plasma (exCT, exPDN-21) before and after calcium (Ca) infusion (2 mg Ca/kg over 5 min) in nine normal men and nine normal women. Plasma CT and immunoreactive PDN-21 levels were often below the assay detection limits. In contrast, basal exCT and exPDN-21 were detectable in all plasma samples, and the concentrations of both were significantly higher in men than in women [basal exCT (mean +/- SE): men, 4.8 +/- 0.3 ng/L; women, 2.4 +/- 0.3 (P less than 0.001); basal exPDN-21: men, 4.7 +/- 0.3 ng/L; women, 3.3 +/- 0.3 (P less than 0.01)]. Ca infusion sharply increased CT and PDN-21 concentrations in both sexes, but the increments were greatest in men [mean (+/-SE) increment of exCT: men, 37.2 +/- 3.9 ng/L; women, 15.7 +/- 4.3 (P less than 0.002); mean increment of exPDN-21: men, 29.7 +/- 4.7 ng/L; women, 11.0 +/- 3.1 (P less than 0.005)]. The molar concentrations of exCT and exPDN-21 were closely correlated (r = 0.97; P less than 0.001). With our antiserum, the extraction-concentration technique for measurement of PDN-21 had increased sensitivity and decreased nonspecific interference compared to the whole plasma assay. We conclude that CT and PDN-21 are cosecreted from normal thyroid C-cells under the control of extracellular fluid Ca, and that men have greater secretory capacity for both peptides than women. Plasma PDN-21 may serve alternatively to CT as a marker for C-cell activity.

Adult↗
PubMed1988

Elevated secretion and action of serum parathyroid hormone in young adults consuming high phosphorus, low calcium diets assembled from common foods.

We sought to determine if the high phosphorus, moderately low calcium intake typical of U.S. teenagers and young adults alters parathyroid function as it does in experimental animals. Because those animals ultimately developed osteopenia, it has been suggested that low dietary calcium to phosphorus ratios may reduce peak bone mass and increase susceptibility to osteoporotic fracture later in life. However, it is not known whether PTH secretion or action increases in response to commonly consumed phosphorus-rich, calcium-poor foods. We studied the 24-h mineral and hormonal responses of eight men and eight women, aged 18-25 yr, after 8 days of ingesting a control diet that had calcium (820 mg) and phosphorus (930 mg) contents near the recommended daily intakes, and a test diet with calcium and phosphorus contents (1660 mg phosphorus, 420 mg calcium) typical of current intakes. Both diets were made from common grocery store foods. The 24-h mean serum immunoreactive PTH levels increased in men (11%; P less than 0.006) and women (22%; P less than 0.003) during the test diet. In both sexes, the test diet significantly increased serum phosphorus, plasma 1,25-dihydroxyvitamin D, and urinary hydroxyproline and cAMP excretion; in women only it decreased serum ionized and total calcium levels. Thus, short term ingestion of a diet typifying current levels of calcium and phosphorus intake resulted in elevated serum iPTH levels and indexes of PTH action in young adults.

Adolescent↗
PubMed1988

Synthetic human parathyroid hormone-(1-34) for the study of pseudohypoparathyroidism.

The synthetic amino-terminal fragment of PTH, PTH-(1-34), was recently released for clinical testing of PTH responsiveness. We measured the urinary cAMP and phosphaturic responses to infusion of PTH-(1-34) [3U/kg BW (200 U maximum), iv in 10 min] in patients with pseudohypoparathyroidism and idiopathic hypoparathyroidism, as well as normal subjects. The protocol used data from 5 30-min urine collections and 4 blood samples. Based on the results in 7 patients with pseudohypoparathyroidism (hypocalcemia with increased serum immunoreactive PTH concentrations), 2 patients with suspected pseudohypoparathyroidism, 9 patients with surgical hypoparathyroidism, and 10 normal subjects, this testing protocol differentiated well among these conditions. The patients with pseudohypoparathyroidism had blunted cAMP and phosphaturic responses to PTH-(1-34) administration compared to those of either normal or hypoparathyroid subjects. Induced hypercalcemia failed to restore a normal cAMP response to PTH-(1-34) infusion in 2 patients with pseudohypoparathyroidism. Calculation of the cAMP response to PTH-(1-34) as nanomoles per dL glomerular filtrate during the first 30 min after infusion provided better differentiation among groups than other parameters of cAMP metabolism. Calculating the phosphaturic response as the percent fall in tubular maximum for phosphate reabsorption during the first hour after infusion gave the best degree of statistical separation among groups. We conclude that this new diagnostic agent is effective for the study of renal responsiveness to PTH, and that the protocol described here reliably differentiates patients with pseudohypoparathyroidism from those with hypocalcemia due to other causes.

Adult↗
PubMed1988

Hypercalcemia.

Hypercalcemia is a relatively common clinical finding; prevalence rates are 1.4 to 3.0 per cent in hospitalized and general clinical populations. Malignancy is the major cause of hypercalcemia in hospital patients, whereas primary hyperparathyroidism (HPT) is the major cause in ambulatory patients. In both hospitalized and ambulatory patients, however, there are many other causes of hypercalcemia, and numerous procedures have been proposed to aid in the differential diagnosis. Unfortunately, no single test is truly diagnostic. The work-up for hypercalcemia requires an integrated knowledge of the strengths and weaknesses of the various procedures as well as an understanding of the various clinical presentations associated with hypercalcemia.

Diagnosis, Differential↗
PubMed1987

Axial and appendicular bone mineral density in patients with long-term deficiency or excess of calcitonin.

Whether calcitonin deficiency causes and calcitonin excess prevents bone loss is controversial. We therefore measured plasma calcitonin levels and bone mineral density at the radius (by single photon absorptiometry) and lumbar spine (dual photon absorptiometry) in patients with an excess or deficiency of calcitonin. We studied 21 patients who had undergone subtotal thyroidectomy 6.8 to 29 years previously and had no calcitonin secretory reserve, and 11 patients who had received a diagnosis of medullary thyroid carcinoma 6.8 to 23 years previously and had chronic hypercalcitoninemia. Bone-density values, expressed as Z-scores (i.e., as the number of standard deviations above or below the normal means adjusted for age and sex), were indistinguishable from normal in the patients who had undergone thyroidectomy (means +/- SE: radius, 0.36 +/- 0.15; spine, 0.27 +/- 0.17). In the patients with medullary thyroid cancer, radial bone-density values were normal (-0.26 +/- 0.39), but spinal density was significantly reduced (-0.75 +/- 0.17, P less than 0.01). There were no significant correlations between the duration of calcitonin excess or deficiency and the bone density at either site. Bone mineral density was not affected by whether or not thyroxine replacement therapy was given. We conclude that skeletal mass is not affected by endogenous plasma calcitonin in adults.

Adult↗
PubMed1987

Effect of age on circulating immunoreactive and bioactive parathyroid hormone levels in women.

Although levels of serum immunoreactive parathyroid hormone (iPTH) increase with age in women, this could be caused by retention of non-biologically active PTH fragments by the aging kidney. In 102 normal women, aged 30 to 89 yr, serum iPTH increased with age by 58% (r = 0.33, p less than 0.001) with antiserum GP-1M (which has midmolecule specificity) and 43% (r = 0.32, p less than 0.001) with antiserum CH-12M (which may have whole molecule specificity); urinary cAMP/GFR excretion increased by 29% (r = 0.22, p less than 0.05). The results of these assays were validated by comparison with serum levels of biologically active PTH (BioPTH) in immunoextracts of serum followed by renal adenylate cyclase assay in a selected subgroup of 25 of the women. Serum BioPTH correlated with serum iPTH assessed by antiserum GP-1M (r = 0.48, p less than 0.05) and antiserum CH-12M (r = 0.48, p less than 0.05) but not with urinary cAMP. The data are consistent with an increase of parathyroid function with aging: clearly, we do not find decreased parathyroid function as would be expected if age-related bone loss was not mediated, in part, by PTH.

Adult↗
PubMed1987

Determination of silica-purified plasma calcitonin for the detection and management of medullary thyroid carcinoma: comparison of two provocative tests.

Radioimmunoassays for human calcitonin in whole plasma are limited in sensitivity and specificity; basal values of calcitonin are often undetectable in normal plasma, and nonspecific increases are occasionally found in seemingly healthy persons. We avoided these problems by applying a silica-cartridge extraction-concentration technique for calcitonin assay, and the effectiveness of two calcitonin stimulation tests in healthy volunteers and patients with medullary thyroid carcinoma was compared. The radioimmunoassay was improved by using a new antiserum and a sequential incubation procedure that reduced the previously used sample-volume requirement and incubation period substantially. This method was used to measure mean basal plasma levels of calcitonin (+/-SD) in 45 normal men (8.2 +/- 5 pg/ml) and 47 normal women (4.8 +/- 4 pg/ml) (P less than 0.001). Calcium infusions (2 mg/kg over 5 minutes) in 18 normal men and 37 normal women yielded a significantly greater secretory response than did pentagastrin (0.5 micrograms/kg as a bolus). Among 12 patients with medullary thyroid carcinoma, pentagastrin seemed to be a better secretagogue than calcium (P less than 0.001). We recommend routine measurement of plasma silica-extractable calcitonin and pentagastrin injection as the provocative test of choice for the detection and management of medullary thyroid carcinoma. The short calcium-infusion test is a good alternative.

Adult↗
PubMed1987

Distribution of serum calcium values in patients with familial benign hypercalcemia (hypocalciuric hypercalcemia): evidence for a discrete genetic defect.

One group has reported hypocalcemic individuals in families affected with familial benign hypercalcemia (FBH), suggesting either that FBH is merely an extreme of normality or that hypocalcemia is independently inherited in that kindred. To test these hypotheses, we examined the distributions of serum total calcium (Ca) values in 260 normal adults and 171 adult individuals in 21 FBH kindreds. We excluded from analysis the 21 adult probands, leaving 85 apparently affected persons (Ca, greater than 10.1 mg/dL or greater than 2.52 mmol/L) and 65 apparently unaffected individuals (Ca, less than or equal to 10.1 mg/dL or less than or equal to 2.52 mmol/L). Five FBH family members were hypocalcemic (less than 8.9 mg/dL or less than 2.22 mmol/L); of these, 3 had hypoproteinemia or hypoalbuminemia, 1 had surgical hypoparathyroidism, and 1 was pregnant (and thus excluded from further analysis). Histogram analysis suggested a bimodal distribution of Ca in the FBH families, and familial serum Ca levels were significantly elevated (P less than 0.001, rank sum). When only apparently unaffected family members were compared with normal individuals with serum Ca of 10.1 mg/dL or 2.52 mmol/L or less, the distributions were virtually identical. Our results indicate that hypocalcemia in members of families with FBH is of sporadic nongenetic origin. Furthermore, FBH is not an extreme of the normal distribution, but, instead, a clear disturbance with its own distribution about a supranormal mean serum calcium value.

Adult↗