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)

The bisphosphonate drug APD (pamidronate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate) has been shown to bind to human plasma proteins. This was an unexpected observation since this hydrophilic, anionic drug is not typical of molecules that exhibit this characteristic. At a concentration of 5 micrograms/ml the extent of binding of APD to fresh human plasma in vitro was variable between subjects 30.2% +/- 8.5% (mean +/- S.D., n = 10). Binding was not influenced by the time or concentration of APD over the range 0.05-10.0 micrograms/ml. At 20 and 50 micrograms/ml some precipitation of APD occurred. Both calcium and iron play a role in the binding of APD to plasma proteins, addition of calcium to plasma increased the degree of binding of APD, whereas the calcium chelators EDTA and EGTA reduced the binding of APD. Similarly, addition of iron to plasma increased the binding and the inclusion of the iron chelator desferrioxamine diminished the binding of the drug. The effects of iron and desferrioxamine were less pronounced than those of calcium and EDTA, indicating that the majority of the binding involves calcium ions and a smaller contribution is made by ferric ions. The equilibrium dissociation constants (Kd) for APD binding to calcium and iron binding sites on plasma proteins were estimated to be 852 microM and 29 microM, respectively. Calcium binding sites were of high capacity but low affinity and the iron binding sites were of lower capacity and higher affinity. Electrophoresis of plasma proteins following incubation with [14C]APD revealed binding to the transferrin and globulin fractions. However, there was some dissociation of protein bound APD during the electrophoresis. The consequences of hypercalcaemia on the pharmacokinetics of APD are discussed.
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PMID:Plasma protein binding of APD: role of calcium and transferrin. 173 Jan 49

The authors report a case, perhaps the first, of immunoglobulin D (IgD) benign monoclonal gammopathy. The patient, a 48-year-old black woman, initially had a 500 mg/dl IgD-lambda M-spike, hypercalcemia, and anemia. There was no bone pain, lytic bone lesions, or evidence of renal failure. The bone marrow showed 2.8% plasma cells with a diffuse (not nodular) IgD plasmacytosis and strong lambda predominance. Only trace amounts of free lambda light chains could be demonstrated by immunoelectrophoresis in serum and concentrated urine. The anemia responded quickly to iron therapy. Chemotherapy was not initiated. Over the 6+ years of follow-up, the patient has had no progression of clinical disease attributable to her IgD monoclonal gammopathy. The IgD M-spike has steadily decreased.
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PMID:Immunoglobulin D benign monoclonal gammopathy. A case report. 190 73

In patients with severe chronic renal failure (SCRF), especially in those undergoing chronic dialysis, aluminium may accumulate in the body. The aluminium is derived from the dialysate and/or from orally-administered, aluminium-containing phosphate binders. Accumulation preferentially occurs in the bone causing aluminium-induced osteomalacia. The physiopathological mechanisms of the disease still have to be elucidated. It has been suggested that aluminium accumulates at the osteoid/calcified-bone boundary (OCBB) inhibiting the influx of calcium there, and also that aluminium directly suppresses the secretion of parathyroid hormone (PTH). A third factor inducing the mineralization defect may be the presence of aluminium within the mitochondria of the osteoblast. In accordance with these hypotheses, hypercalcemia and relatively low iPTH levels are frequently found in aluminium-induced osteomalacia. Histologic methods are essential for demonstrating the actual existence of aluminium-induced osteomalacia. A large bone biopsy is desirable. When the biopsy is not decalcified and embedded in plastic, excellent histologic pictures are obtained wherein mineralized and non-mineralized bone (i.e. osteoid) can be distinguished clearly. Furthermore, the un-decalcified sections can be stained for aluminium, iron or both, and they are suitable for evaluation of the bone marrow status. Several features, like irregularly distributed osteoid with variable thickness, a relatively low number of cubic osteoblasts, and the absence of marrow fibrosis, are suggestive of aluminium-induced osteomalacia. However, the latter can only be proven by histochemical methods, e.g. by the aluminon staining. The treatment of aluminium-induced osteomalacia is quite different from that of other types of renal bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aluminium-induced osteomalacia in severe chronic renal failure (SCRF). 391 58

Increased renal uptake of 99mTc methylene diphosphonate (MDP) was observed irregularly in rats after methotrexate, vincristine or gentamicin, administered separately. Cisplatin regularly induced a dose-related increased MDP uptake which correlated with the degree of tubular damage histologically. The augmented MDP renal uptake was not consistently accompanied by a decreased clearance of simultaneously injected I-131 Hippuran, particularly at lower drug dose levels. This observation agreed with previous evidence that the mechanisms of tubular transport of diphosphonates and organic acids like Hippuran are different. At higher dose levels, the augmented MDP uptake was accompanied by increased renal calcium, hypophosphatemia, elevated serum urea nitrogen and creatinine, and only occasional, mild hypercalcemia. The magnitude of the increased renal uptake of MDP observed could not be explained by alterations in iron metabolism or by dehydration. Drug-induced renal retention of MDP by a factor of 2 or more above normal appears to be a useful indicator of tubular damage when other parameters of renal function are sometimes normal.
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PMID:Experimental drug-induced changes in renal function and biodistribution of 99mTc-MDP. 622 84

Calciphylaxis is a local tissue calcific reaction at the site of an injection of challenger substance given a critical time period after the oral administration of a sensitizer substance such as dihydrotachysterol (DHT), vitamin D or parathormone. Cutaneous calciphylaxis is readily induced in the rat but not in the mouse and this may be because, in the latter, the challenger substance is absorbed rapidly by macrophages. In the rat the administration of 500 micrograms/0.1 ml of DHT followed after 24 h by the subcutaneous (SC) injection of ferric chloride (FeCl3) (30 micrograms/0.1 ml) is followed rapidly by calcification of the SC site. There is an early transient acute inflammatory reaction with the incrustation of collagen fibres by the iron salt and an apparent exudation of calcium and phosphate ions from the bloodstream. These ions also become associated with collagen fibres. Two days after injection macrophages and multinucleated giant cells become the dominant cells. Calciphylaxis is a useful experimental model of ectopic calcification and is associated with an initial hypercalcaemia. The diphosphonates ethane-1-hydroxy-1, 1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl2MDP) are effective inhibitors of the calciphylactic reaction when administered prior to the initiation of the experimental procedure.
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PMID:Cutaneous calciphylactic reactions in the mouse and the rat and the effects of diphosphonates on the reaction in the rat. 623 Apr 25

Therapy of the malabsorption syndrome centers on adequate diagnosis of the underlying pathology, with vigorous therapeutic efforts directed at correcting this and thereby preventing ongoing losses of nutrients. Dietary therapy includes a high-protein, high-calorie, low-fat diet often supplemented with MCTs in an effort to minimize steatorrhea. Water-soluble vitamin deficiency is rare, but supplementation with small daily doses is innocuous and probably should be prescribed. Significant fat-soluble vitamin deficiencies are seen more commonly and can be monitored by physical examination and the prothrombin time. Calcium, magnesium, and vitamin D deficiencies are more common than originally suspected. Adequate therapy requires monitoring of the serum calcium, magnesium, parathyroid hormone levels, and, optimally, 24-hour urinary collections for calcium. Supplementation of these mineral deficiencies requires ongoing close observation to prevent hypercalcemia. Iron deficiency can be easily diagnosed by available serum iron determination, and replacement with oral supplements is curative. Trace metal deficiencies occur, but our capabilities of detecting and treating them is still in its infancy. Figure 3 outlines our approach to the evaluation and treatment of the patients suspected of having the malabsorption syndrome.
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PMID:Nutritional aspects of malabsorption syndromes. 641 33

A 63-year-old man with iron loss anaemia and hypercalcaemia was found to have a renal cell carcinoma. Despite the iron-deficient blood and bone marrow picture, the serum ferritin concentration was markedly raised. This was mainly due to a "basic isoferritin". The serum parathormone concentration was normal. The serum ferritin and calcium concentrations returned to normal after the tumour was removed. We propose that the renal cell carcinoma cells in this patient secreted the basic isoferritin as well as humoral factor(s) responsible for hypercalcaemia.
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PMID:Basic isoferritin and hypercalcaemia in renal cell carcinoma. 711 19

Adynamic (or aplastic) bone disease is a bone histologic pattern characterized by decreased bone formation rate, low cellularity, and normal or decreased osteoid thickness. It was first described in symptomatic patients undergoing dialysis who were overloaded with aluminum because of contaminated dialysate or chronic ingestion of aluminic phosphate binders; the evidence of the overload was extensive coloration (more than 25%) with aurin tricarboxylic acid, whereas the Perls stain coloration for iron was negative. We have, however, reported these histologic changes in asymptomatic patients with uremia who were never exposed to aluminum, in two patients before end-stage renal failure and in six patients undergoing dialysis. The main step in the prevention of adynamic bone disease is the absolute exclusion of aluminum exposition even by so-called "safe doses" of aluminum phosphate binders because in the long term they are never actually safe. Because idiopathic adynamic bone disease may nevertheless occur, parathyroid hormone suppressive treatment by oral calcium taken with meals as phosphate binders (+/- 1 alpha-hydroxyvitamin D3 derivatives) should be carefully monitored by measurements of plasma concentrations of not only calcium and phosphate but also of intact parathyroid hormone levels. In order to have normal bone formation rate levels, patient intact parathyroid hormone levels should be between one and three times the upper limit of the normal level. Although adynamic bone disease may not be a true bone disease when not due to aluminum, it is a risk factor for increased incidence of hypercalcemia and hyperphosphatemia and therefore for metastatic calcifications. Therefore, when hypercalcemia occurs with hyperphosphatemia and normal intact parathyroid hormone in patients treated with 1 alpha-hydroxyvitamin D3, it is proposed that the latter drug should be discontinued first, whereas oral calcium is increased to correct hyperphosphatemia, and calcium concentration is decreased in the dialysate to prevent hypercalcemia, even though plasma parathyroid hormone may increase up to three times the upper limit of the normal level. In patients previously exposed to aluminum, a deferoxamine test should be performed and a deferoxamine treatment started if the test is positive.
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PMID:Adynamic bone disease in patients with uremia. 807 43

Treatment for the paraneoplastic syndrome associated with lung cancer was reviewed. The principle of the treatment of paraneoplastic syndrome is to control cancer as an underlying disease. Therefore, the standard therapy for Cushing's syndrome associated with lung cancer is surgical treatment if the tumor is operable. There is no standard therapy for Cushing's syndrome associated with advanced small-cell lung cancer. Metyrapone is used in combination with systemic chemotherapy. The effects of ketoconazole and octreotide are under investigation. To control hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion, fluid restriction is standard. When hyponatremia cannot be controlled with fluid restriction, demeclocycline can be used. For life-threatening hyponatremia, hypertonic saline with intravenous furosemide is administered under careful monitoring. Followed by hydration with saline, pamidronate is effective for the control of symptomatic hypercalcemia. Combined use of calcitonin facilitates rapid normalization of serum calcium for critically ill cases. Heparin is used for patients with recurrent episodes of thrombosis resulting from chronic disseminated intravascular coagulation, although the efficacy is controversial. Thrombocytes and coagulation factors are combined with heparin for patients with uncontrollable bleeding, although the efficacy is not established.
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PMID:[Paraneoplastic syndrome]. 936 21

Calcium salts, such as calcium carbonate and calcium acetate, are the principal compounds used as phosphate binders in patients with chronic renal failure. The dose required is three to six times the normal requirement for calcium. Use of these large doses of calcium salts in the diet can result in hypercalcemia. Other compounds have been investigated as phosphate binders with varying degrees of success. Synthetic ferrihydrite (5Fe(2)O(3).9H(2)O) has a high adsorptive capacity for phosphate and may be an effective phosphate binder. The phosphate-binding capacity of ferrihydrite was compared with that of calcium acetate in 250-g male Sprague Dawley rats. After an overnight fast, rats (n = 5 per group) were gavaged with an American Institute of Nutrition (AIN) 76 formula containing one third the daily phosphorus intake labeled with phosphorus-32 ((32)P). Either two levels of calcium acetate, representing three (1/2X) or six (1X) times the usual calcium intake for one third of the day, or equivalent amounts of ferrihydrite were added to the diet. An additional group received two times (2X) the larger dose, and a sixth control group received no binder in the diet. Phosphorus absorption curves were determined from (32)P appearance in the serum. The 1/2X dose of ferrihydrite reduced (32)P by approximately one half, and the 2X dose nearly completely suppressed (32)P absorption, similar to the 1X dose of calcium acetate. The advantage of using a ferrihydrite binder would be to avoid the hypercalcemia resulting from the use of high-dose calcium salts. An added advantage may result from the small amounts of iron absorbed in these chronically iron-deficient patients.
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PMID:Phosphate-binding capacity of ferrihydrite versus calcium acetate in rats. 1043 Sep 81


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