Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten uraemic patients on regular haemodialysis were treated with 1alpha-hydroxycholecalciferol (1alpha-H.C.C.) for 5 to 14 months. Five patients who had histological osteitis fibrosa with or without osteomalacia responded well, with resolution of musculoskeletal pain, return of raised serum-alkaline-phosphatase concentrations to normal, resolution of radiological subperiosteal erosions, and improvement in histological signs of osteitis fibrosa and osteomalacia. In these patients 1alpha-H.C.C. proved a safe and effective drug. Five other patients did not improve. Characteristically these patients started with moderately severe histological osteomalacia and minimal, if any, osteitis fibrosa. Proximal myopathy was a prominent symptom and serum-alkaline-phosphatase was normal in four of them. Treatment with 1alpha-H.C.C. resulted in early troublesome hypercalcaemia, and repeat bone histology 5--11 months later showed no improvement. It is suggested that in these patients lack of 1,25-dihydroxycholecalciferol may not have been wholly responsible for the observed osteomalacia, hence 1alpha-H.C.C. alone was ineffective. Phosphate depeltion may have been an important contributing factor.
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PMID:Variable response to long-term 1alpha-hydroxycholecalciferol in haemodialysis osteodystrophy. 5 5

The use of oral calcium carbonate as a phosphate binder is often complicated by hypercalcaemia, particularly with concomitant use of vitamin D analogues. We previously found that stepwise reduction of dialysate calcium effectively countered this complication in haemodialysis patients, and have now assessed the strategy in CAPD patients. Seventeen patients underwent conversion from aluminium hydroxide to calcium carbonate and were followed for 5 months, with subsequent addition of alfacalcidol for a further 5 months. Standard CAPD dialysate (1.75 mM calcium) was used, reducing to 1.45 mM and, if necessary, to 1.00 mM in patients who became hypercalcaemic. While receiving calcium carbonate alone, 12 of the 17 patients became hypercalcaemic, this responding in four to dialysate calcium reduction to 1.45 mM. In the remaining eight patients, further reduction to 1.00 mM was required and in two patients even this failed to control hypercalcaemia adequately, necessitating reversion to aluminium hydroxide. Phosphate control remained unchanged, as did calcium x phosphorus product. There were transient increases of blood ionised calcium, and decreases of parathyroid hormone, with progressive reduction of serum aluminium and alkaline phosphatase. The addition of alfacalcidol (0.25 microgram/day) led to hypercalcaemia in six subjects, successfully countered by dialysate calcium reduction in four. The results show that standard CAPD dialysate calcium at 1.75 mM is too high for the majority of calcium carbonate treated patients and that substantial reductions of the dialysate calcium concentration are required if calcium carbonate is to be used effectively.
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PMID:Dialysate calcium reduction in CAPD patients treated with calcium carbonate and alfacalcidol. 131 83

Oral calcium carbonate is an effective phosphate binder in dialysis patients. Its use minimizes aluminium intake, and by maintaining a high-normal serum ionized calcium, suppresses serum parathyroid hormone levels. However, the dose required to control hyperphosphataemia may cause hypercalcaemia. We performed prospective studies in 50 previously undialysed patients starting CAPD (28 study group, 22 control group). Calcium carbonate was the only phosphate binder used in the study group which utilized a low calcium PD fluid (calcium 1.25 mmol/l), whilst the control group used standard PD solution (calcium 1.75 mmol/l) with calcium carbonate plus aluminium hydroxide phosphate binders as clinically indicated. The study group was able to take larger doses of oral calcium carbonate with no increase in episodes of hypercalcaemia compared to the control group. There were no instances of hypocalcaemia in any patient using the low-calcium dialysis fluid. Phosphate control was better in the study group, despite the additional use of aluminium-containing phosphate binders by some patients in the control group. Serum aluminium levels in the study group were maintained at < 11.5 mumol/l, but increased significantly in the control group from 3 months onward. Mean serum parathyroid hormone in the study group declined significantly from baseline values over the first 6 months, and remained at the lower level. Bone histology showed a tendency towards improvement over the 12 months, in terms of osteoclast numbers and activity. We conclude that using dialysis fluid with a reduced calcium concentration in compliant, well-monitored patients is safe.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-calcium dialysis fluid and oral calcium carbonate in CAPD. A method of controlling hyperphosphataemia whilst minimizing aluminium exposure and hypercalcaemia. 133 63

At start of dialysis most patients have histological bone abnormalities. These can be divided into two groups--high turnover and low turnover bone disease. Low turnover aplastic disease was previously attributed to aluminum accumulation but is now known to occur even in patients with less than 5% surface stainable aluminium. It is characterised by a mineralisation defect, thin osteoid seams, decreased numbers of osteoclasts and osteoblasts and absent aluminium staining. We have avoided aluminium containing phosphate binders (ACPBs) completely, with a combination of oral calcium carbonate and "low calcium" (1.25 mMol/l) dialysis fluid. Phosphate control has been good (mean less than 1.6 mMol/l) and over the first twelve months serum PTH levels have fallen significantly. Transient asymptomatic episodes of hypercalcaemia have occurred but no patient required ACPBs. Bone biopsies at the start of CAPD in 34 patients showed over 50% to have osteitis fibrosa (OF) but in five cases (15.6%) the aplastic lesion was found without aluminium staining. In seven follow-up biopsies OF improved in 3 cases, osteomalacia improved in 1, became aplastic in 1, while aplastic bone worsened in 1 and changed to mild OF in 1. We conclude that the predominant bone lesion in our patients at start of CAPD is OF, but 15% already have aplastic bone. "Low calcium" dialysis fluid enables ACPBs to be avoided in the majority of CAPD patients.
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PMID:Renal osteodystrophy in CAPD. 168 Apr 34

In order to suppress the parathyroid glands by inducing hypercalcemia, young rats were fed a diet containing a low (0.02%) phosphate content. After 28 days blood samples were taken for estimation of serum calcium, phosphate and immunoreactive parathyroid hormone levels. Both parathyroids from each animal were subjected to serial sectioning so that the total glandular volume could be calculated by light microscopy. Volume and surface densities of cells and organelles were measured according to conventional stereological principles, so that the total volumes and surface areas could be estimated. Phosphate depletion caused marked growth retardation. The animals also developed hypophosphatemia, but in spite of pronounced hypercalcemia the levels of circulating immunoreactive parathyroid hormone remained unchanged. The volume of the parathyroids was reduced, but only to an extent commensurate with the reduced body mass. In the experimental group the volume density of cells was unchanged, but that of nuclei was increased; the volume density of Golgi complexes was reduced. The densities of the other cell components measured, namely the volume density of mitochondria and the surface densities of secretory cells, nuclear membranes and rough endoplasmic reticulum were unchanged. When the volumes and surfaces were expressed in absolute terms and related to total body mass, no differences between the groups were apparent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stereological studies of the parathyroids in the young rat with hypercalcemia induced by severe phosphate depletion. 290 Nov 63

Phosphate indices (serum phosphate, tubular reabsorption of phosphate, renal threshold phosphate concentration (TmP/GFR) and index of phosphate excretion) were studied in 88 hypercalcaemic subjects: 64 with primary hyperparathyroidism (HPT) and 24 with hypercalcaemia from other causes, predominantly malignant disease. HPT patients as a group could easily be separated from normal subjects (n = 16) and patients with functional hypoparathyroidism (n = 7) by use of the phosphate variables but these indices were of little discriminating value for the differential diagnosis between HPT and hypercalcaemia from other causes. There was no difference in the urinary cyclic adenosine monophosphate (cAMP) excretion between the two hypercalcaemic patient groups, but HPT patients had clearly elevated serum parathyroid hormone (PTH) levels compared with normal PTH concentrations in patients with other causes of hypercalcaemia. A positive correlation between cAMP and serum calcium and an inverse relationship between cAMP and TmP/GFR were found in patients with hypercalcaemic malignant disease. These findings suggest the existence of a humoral factor with PTH-like effects in malignant disease. Since PTH levels were low, the physiological actions were apparently not mediated by circulating PTH. No difference in the values for phosphate variables, PTH, cAMP or serum calcium was found between renal stone-forming and stone-free patients with HPT.
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PMID:Clinical studies on phosphate handling in hypercalcaemia. 629 62

Two siblings (boy and girl) born to a mother with familial hypophosphatemic rickets had abnormal values of serum phosphorus and serum alkaline phosphatase at the age of six weeks. At this age therapy with 1 alpha-hydroxycholecalciferol (1 alpha OHD3) and phosphate was started resulting in both siblings having normal growth of body length and radiological healing of the bone lesions but persistently low values of fasting serum phosphorus during the time of observation up to 60 and 26 months of age, respectively. Phosphate and 1 alpha OHD3 have a positive influence on serum phosphorus through their effect on the intestine. Neither of the patients developed hypercalcaemia during treatment. It seems, therefore, that the early administration of 1 alpha OHD3 with phosphate in infants with familial hypophosphatemic rickets prevents dwarfism and has a positive effect on intestinal absorption of phosphorus but not on fasting hypophosphatemia.
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PMID:The management of siblings with familial hypophosphatemic rickets. 665 89

A radioimmunoassay for human parathyrin has been developed and characterized with whole-molecule (residues 1-84) human parathyrin and with the 1-34, 44-68, and 53-84 amino acid residue fragments of it. The antiserum used reacted with the whole molecule and with the 44-68 and 53-84 fragments, but not with the 1-34 fragment. Parathyrin concentrations in the serum of 118 normal subjects and of 112 patients with surgically proved primary hyperparathyroidism were determined with this assay. The mean results were 39 (SD 13) microL-Eq/mL for the normals and 111 (SD 77) microL-Eq/mL for the patients with primary hyperparathyroidism (p less than 0.0005). The upper 95% confidence limit of the normal range was 60 microL-Eq/mL. For 54 patients with primary hyperparathyroidism, the preoperative values for serum parathyrin, calcium, and phosphate--but not creatinine--were statistically different from the postoperative values (paired t-test, p less than 0.0005). Normal subjects showed significant (p less than 0.0005) differences in serum calcium concentrations but not in parathyrin concentrations, compared with concentrations found in cancer patients and patients who had thiazide-induced hypercalcemia. Phosphate concentration in serum, although not a specific indicator of disease, is a valuable clue to the diagnosis of primary hyperparathyroidism.
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PMID:Development and validation of a new radioimmunoassay for parathyrin (PTH). 705 38

The effect of phosphate deprivation on urinary acidification was investigated in rats fed a phosphate-deficient diet and in control rats fed the same diet supplemented with phosphate. Phosphate-deprived animals developed hypophosphatemia, hypercalcemia, and hypophosphaturia, but failed to develop hyperchloremic metabolic acidosis following 30 or 60 days of phosphate deprivation. Baseline urine pH was significantly higher in phosphate-deprived rats than in controls, but baseline urine HCO3 excretion was not significantly different between the two groups. The pattern of HCO3 reabsorption in phosphate-deprived rats was identical to that of controls at both low and high plasma HCO3 levels. During chronic NH4Cl administration, both 30- and 60-day phosphate-deprived rats had a sigificantly higher minimal urine pH and lower titratable acid and net acid excretion than seen in controls. NH4 excretion was significantly lower than controls in the 60-day phosphate-deprived rats only. During Na2SO4 administration the minimal urine pH was significantly lower in controls than in phosphate-deprived rats, but there was overlap of urine pH values. At comparable levels of urine pH, NH4 excretion was significantly lower in phosphate-deprived rats than in controls. Phosphate-deprived rats were able to raise urine-blood CO2 pressure to the same levels as controls during both HCO3 loading and Tris buffer administration. Phosphate-deprived rats had greater extrarenal buffering capacity than controls as evidenced by a lower decline in blood pH and HCO3 during HCl infusion in phosphate-deprived rats. These data demonstrate that phosphate deprivation is associated with distal acidification defect, impaired NH3 excretion, and increased extrarenal buffering capacity. The increased availability of buffer in phosphate deprivation may play an important role in acid-base homeostasis in this condition.
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PMID:Distal acidification defect induced by phosphate deprivation. 741 57

Phosphate is central to bone metabolism and we have therefore studied whether parathyroid hormone (PTH) is regulated by dietary phosphate in vivo. Weanling rats were fed diets with different phosphate contents for 3 wk: low phosphate (0.02%), normal calcium (0.6%), normal phosphate (0.3%), and calcium (0.6%); high phosphate (1.2%), high calcium (1.2%). The low phosphate diet led to hypophosphatemia, hypercalcemia, and increased serum 1,25(OH)2D3 together with decreased PTH mRNA levels (25 +/- 8% of controls, P < 0.01) and serum immunoreactive PTH (4.7 +/- 0.8: 22.1 +/- 3.7 pg/ml; low phosphate: control, P < 0.05). A high phosphate diet led to increased PTH mRNA levels. In situ hybridization showed that hypophosphatemia decreased PTH mRNA in all the parathyroid cells. To separate the effect of low phosphate from changes in calcium and vitamin D rats were fed diets to maintain them as vitamin D-deficient and normocalcemic despite the hypophosphatemia. Hypophosphatemic, normocalemic rats with normal serum 1,25(OH)2D3 levels still had decreased PTH mRNAs. Nuclear transcript run-ons showed that the effect of low phosphate was posttranscriptional. Calcium and 1,25(OH)2D3 regulate the parathyroid and we now show that dietary phosphate also regulates the parathyroid by a mechanism which remains to be defined.
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PMID:Parathyroid hormone gene expression in hypophosphatemic rats. 761 2


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