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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphate binders that contain aluminum or calcium are frequently prescribed to treat hyperphosphatemia in patients with end-stage renal disease (ESRD), but an accumulation of aluminum can lead to encephalopathy, aluminum-related bone disease (ARBD) such as osteomalacia, anaemia, and resistance to erythropoietin, and calcium accumulation can lead to hypercalcaemia. High phosphate concentrations are reduced in vitro and in vivo by a phosphate adsorption pill, which is synthesized by hydrolyzing ferrous sulfate in the presence of saccharides, to form an iron (III)-saccharide complex that is acid resistant and binds phosphate greater than iron (III) hydroxide alone. Under in vitro conditions, containing 3.26 mg P/dL, the iron (III)-sucrose complex showed the highest phosphate adsorption capacity at pH 2 with artificial gastric juice, 58.9 mg P/g binder. For the 7 day in vivo study, 0% (Group 1), 1% (Group 2), 4% (Group 3), and 8% (Group 4) iron (III)-sucrose complex was admixed into the rodent chow by weight and fed to 15 male Wistar rats. The weight and volume of the feces and urine, and the calcium, iron, and phosphorus excretions in the feces and urine samples were monitored for any signs of irregularity. Total urine outflow was collected during a 24-h period to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The fecal iron excretion was significantly effected by the amount of binder ingested throughout the study for Group 2 (p < 0.001), Group 3 (p < 0.01), and Group 4 (p < 0.001). The urinary calcium excretion (mg/rat/24-h) significantly increased by the 7th day for Group 2 (p < 0.05) and Group 4 (p < 0.01) in comparison to the control. Finally, after 7 days, there was a significant drop in the urinary phosphorus levels (mg P/rat/24-h) in a dose dependent manner for Group 2: from 7.82 +/- 1.46 to 1.98 +/- 0.10 mg P/rat/24-h (102 mg P/dL/24-h; p < 0.05); Group 3: from 6.70 +/- 1.14 to 0.16 +/- 0.09 mg P/rat/24-h (6.0 mg P/dL/24-h; p < 0.01); and Group 4: from 8.25 +/- 0.67 to 0.04 +/- 0.01 mg P/rat/24-h (0.9 mg P/dL/24-h; p < 0.01). The results show that this new adsorbent might provide an alternative to conventional aluminum and calcium containing phosphate-binding agents for combating hyperphosphataemia.
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PMID:Oral phosphate binders: phosphate binding capacity of iron (III) hydroxide complexes containing saccharides and their effect on the urinary excretion of calcium and phosphate in rats. 1051 89

Uremic patients on maintenance hemodialysis are in positive phosphate balance. This is mainly the result of the complex elimination kinetics of phosphate during dialysis. Removal of phosphate is less than net dietary intake. Classical phosphate binders such as calcium carbonate, calcium acetate, and aluminum-based compounds are limited by side effects (hypercalcemia) and outright toxicity (aluminium). There have been numerous recent attempts to develop alternative phosphate binders, e.g., polyallylamine-hydrochloride (Renagel), lanthanum carbonate, and trivalent iron-containing compounds. The latter is based on old observations that iron salts may cause hyperphosphatemia and rickets in experimental animals and in patients. This idea has recently been taken up again, and effective inhibition of net intestinal phosphate uptake in non-uremic and uremic rats has been shown using simple iron salts (citrate, chloride, ammonium citrate) and complex compounds (cross-linked dextran and stabilized polynuclear iron hydroxide). In uremic rats, the latter compound reduces urinary phosphate excretion as an indicator of reduced intestinal phosphate uptake and has also been shown to be effective in subjects with preterminal renal failure. So far, no side effects or short-term toxicity has been observed. The compound appears promising and deserves further evaluation.
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PMID:Phosphate binders on iron basis: a new perspective? 1063 63

Hyperphosphataemia in haemodialysis patients is associated with secondary hyperparathyroidism and more importantly with an increased cardiovascular mortality in dialysed patients. Removal of phosphate during dialysis is less than net intestinal uptake. This imbalance results in a positive phosphate balance. To control serum phosphate concentration oral phosphate binders have to be taken to reduce net intestinal uptake. The use of classical phosphate binders such as calcium carbonate, calcium acetate and aluminium-containing phosphate binders is limited by their side effects. Hypercalcaemia aggravates vascular calcification and cardiovascular risk. Aluminium intoxication causes aluminium osteopathy, anaemia and encephalopathy. Therefore, the development of calcium- and aluminium free phosphate binders has become a challenge to clinical nephrology. Polyallylamine hydrochloride (sevelamer) is one of the new alternative compounds which has been shown to effectively bind phosphate in dialysis patients. A promising approach in the development of alternative phophate binders are trivalent-iron (Fe(III)) containing phosphate binders. They were not only successfully tested in experimental animals but have also been shown to reduce urinary phosphate excretion and serum phosphate concentrations in patients with preterminal failure and those on maintenance haemodialysis. This review outlines the experimental and clinical data on Fe-III based phosphate binders providing evidence that they will be as effective and safe as phosphate binders without the major side effects of classical phosphate-binding compounds.
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PMID:Compounds in development to combat hyperphosphataemia. 1177 14

Phosphate (Pi) retention is a common problem in patients with chronic kidney disease, particularly in those who have reached end-stage renal disease (ESRD). In addition to causing secondary hyperparathyroidism and renal osteodystrophy, recent evidence suggests that, in ESRD patients, high serum phosphorus concentration and increased calcium and phosphorous (Ca x P) product are associated with vascular and cardiac calcifications and increased mortality. Dietary phosphorus restriction and Pi removal by dialysis are not sufficient to restore Pi homeostasis. Reduction of intestinal Pi absorption with the use of Pi binders is currently the primary treatment for Pi retention in patients with ESRD. The use of large doses of calcium-containing Pi binders along with calcitriol administration may contribute to over-suppression of parathyroid hormone secretion and adynamic bone disease as well as to a high incidence of vascular calcifications. When used in patients with impaired renal function, aluminium salts were found to accumulate in bone and other tissues, resulting in osteomalacia and encephalopathy.Sevelamer, an aluminium- and calcium-free Pi binder can reduce serum phosphorus concentration and is associated with a significantly lower incidence of hypercalcaemia, while maintaining the ability to suppress parathyroid hormone production. An additional benefit of sevelamer is its ability to lower low density lipoprotein-cholesterol and total cholesterol levels. Sevelamer attenuates the progression of vascular calcifications in haemodialysis patients, which may lead to lower mortality. The use of sevelamer in non-dialysed patients might aggravate metabolic acidosis, common in these patients. Several other calcium-free Pi binders are in development. Lanthanum carbonate has shown significant promise in clinical trials in ESRD patients. Magnesium salts do not offer a significant advantage over currently available Pi binders. Their use is restricted to patients receiving dialysis since excess magnesium must be removed by dialysis. Iron-based compounds have shown variable efficacy in short-term clinical trials in small numbers of haemodialysis patients. Mixed metal hydroxyl carbonate compounds have shown efficacy in animals but have not been studied in humans. Major safety issues include absorption of the metal component with possible tissue accumulation and toxicity.
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PMID:Safety of new phosphate binders for chronic renal failure. 1464 Jul 73

Mortality from non-Hodgkin's lymphoma (NHL) is high, thus defining the need for additional therapeutic agents for this disease. Gallium nitrate is a metal compound that is presently approved for the treatment of hypercalcaemia associated with malignancy. In clinical trials first conducted over two decades ago, this drug was found to have antineoplastic activity in NHL. However, its development as an antineoplastic agent for the treatment of NHL was never rigorously pursued. Gallium has unique mechanisms of action that include its binding to transferrin in the circulation and targeting transferrin receptors present on lymphoma cells. As it shares chemical properties with iron, gallium can disrupt critical steps in iron homeostasis that are essential for tumour cell viability and growth and can inhibit the iron-dependent activity of ribonucleotide reductase. The drug may also target other cellular processes unrelated to iron. Phase I/II studies have shown that gallium nitrate displays the most efficacy and lowest toxicity in NHL when administered as a continuous intravenous infusion, producing response rates of 43% in patients with relapsed or refractory NHL. It does not suppress the white blood cells or platelets and does not share cross-resistance with other chemotherapeutic drugs. These characteristics make it particularly attractive for the treatment of myelosuppressed patients and for incorporation into combination therapy. Multi-institutional Phase II clinical trials are in progress to evaluate gallium nitrate as a single agent or in combination. These studies will help define its role in the current treatment of NHL.
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PMID:Gallium nitrate for the treatment of non-Hodgkin's lymphoma. 1515 28

Arthritis is inflammation in a joint often with joint damage, usually accompanied by pain, swelling and stiffness, resulting from infection, trauma, degenerative changes, metabolic disturbances, autoimmune or other causes. It occurs in various forms, including rheumatoid arthritis, osteoarthritis, bacterial arthritis and gout. Gallium III can inhibit the production of inflammatory cytokines, such as IL-1beta, produced by macrophage-like cells in vitro. A dose-dependent inhibition of IL-1beta and TPA stimulated MMP activity by gallium nitrate at increasing concentrations occurs, demonstrating that gallium nitrate can be a useful modulator of inflammation in arthritis. Gallium III is an inhibitor of bone resorption and is an effective treatment for hypercalcemia. Gallium III has been reported to be effective in the treatment of mycobacterium butycicum-induced arthritis in rats by antagonism of iron III. Long-term elimination of pain from arthritis by gallium III was first observed in horses primarily being treated for navicular disease. Several people treating their horses with gallium nitrate coincidentally found that arthritis pain in their fingers ended and did not return after soaking their hands in 14% gallium nitrate solution. Therefore, the severely arthritic hands of a 60-year-old woman were topically treated with a 14% aqueous solution of gallium nitrate for 90 min. Pain and inflammation from rheumatoid arthritis diminished rapidly, and neither pain nor inflammation returned during the following 2 years from that single treatment. A 61-year-old woman who had osteoarthritis in her left knee, shoulders and wrists was treated orally with 50 ml of a 1% gallium nitrate solution (120 mg elemental gallium) daily using a two week on and two week off protocol, resulting in almost total elimination of pain while on gallium nitrate, while pain partially returned during the two week off periods. Treatment of frozen shoulder with topical 40% gallium nitrate for 120 min resulted in greatly reduced pain and crepitus almost immediately with complete restoration of range of motion, with pain remaining essentially absent for over 1 year. Mechanisms of action are hypothesized to include anti-inflammatory, bone density improvements, antibacterial, anti-iron III and anti-aluminum III effects. Proper use of gallium III may be effective in terminating pain and inflammation of arthritis for years, often with a single treatment.
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PMID:Elimination of arthritis pain and inflammation for over 2 years with a single 90 min, topical 14% gallium nitrate treatment: case reports and review of actions of gallium III. 1612 80

Cytokines have not been employed in clinical laboratory tests because of the many biological activities of individual cytokines and too complicated cytokine network. However, abnormal laboratory data and symptoms can be interpreted by blood cytokine levels. [Cytokines attributable to abnormal data and symptoms] For example, cytokines attributable to abnormal data and symptoms in rheumatoid arthritis are as follows: joint pain: TNFalpha, IL-1, IL-6, and IL-18; general fatigue and appetite loss: TNFalpha and IL-1; leukocytosis: G-CSF produced by IL-1-stimulated macrophages etc; thrombocytosis: megakaryocyte potentiating activity of IL-6; anemia: hepcidin up-regulated by IL-6, which inhibits iron absorption from the intestine, and IL-1, which decreases the blood iron level and promotes ferritin synthesis. [Differential diagnosis using blood cytokine levels] Blood cytokine levels are useful and important in the differential diagnosis of inflammatory disorders such as neutrophilia, eosinophilia, and especially in distinguishing tumoral fever from infectious fever in malignant lymphomas. [Disease/disorder-specific cytokines] In recent years, disease- or disorder specific cytokines have been identified, making cytokines more important in clinical use. For example, IL-18 for adult-onset Still disease; IFNgamma for hemophagocytic syndrome; IL-5 for allergic disorders; thrombopoietin for immune thrombocytopenic purpura; vascular endothelial growth factor for POEMS syndrome; PTH-rP for malignancy associated hypercalcemia. [Flow cytometric measurement of cytokines] Recently, a flow cytometric method has been developed in addition to ELISA. With this method, 30 cytokine concentrations can be measured simultaneously within four hours with a wide range of detection limit and high cost performance. Cytokines will be included in laboratory tests with this method.
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PMID:[Blood cytokine levels as a clinical laboratory test]. 1744 72

Prostaglandins (PGs) are active biologic substances that are involved in a wide range of physiologic processes; when their production is out of balance, they are factors in the pathogenesis of illness. Modulation of PGs by inhibition or stimulation is promising for the management of various conditions. PG inhibitors are widely used to relieve pain and inflammation in patients with rheumatologic disease. Interest in the use of PG inhibitors to prevent cancer and cardiovascular events is growing. More than 27 y ago, investigators found that PG depresses antibody production in vivo; reduces serum iron, hemoglobin, and leukoid series in bone marrow during acute and chronic blood loss; reduces albumin during antigenic stimulation; suppresses hypercalcemia after bleeding; and reduces fasting blood sugar and hyperglycemia after ether anesthesia and bleeding. Chronic conditions that produce large quantities of PGs are associated with immunosuppression and secondary anemia. Investigators in the present study hypothesized (1) that the overproduction of PGs is responsible for immunosuppression and secondary anemia in conditions associated with increased PG synthesis, such as pathologic inflammation, malignancy, trauma, and injury, and (2) that PG inhibitors reverse immunosuppression and secondary anemia, thereby enhancing the immune response. This is supported by many reports that show the immunosuppressive effects of PGs and their role in the immunosuppression associated with pathologic inflammation, burns, trauma, and tumors. Inhibition of PGs can be achieved through the use of synthetic medicines and natural products. This article reviews the effects of PGs and inhibition of increased synthesis of PGs on the lymphoid system, hematologic indices, and bone marrow elements in trauma, injury, burns, and tumors. The Medline database (1966-2006) was used in this study. Investigators in the present study and others have provided evidence that shows the involvement of PGs in immunosuppression and secondary anemia, as well as the efficacy of inhibited overproduction of PGs in many pathologic conditions other than rheumatologic disease.
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PMID:Modulation of prostaglandin activity, part 1: prostaglandin inhibition in the management of nonrheumatologic diseases: immunologic and hematologic aspects. 1752 77

Long term administration of calcitriol (1,25 - dihydroxyvitamin D) is recommended for the treatment of a number of endocrine and renal disorders associated with impaired calcium - phosphate metabolism. Administration of calcitriol, however, may give rise to undesirable side effects, such as hypercalcemia and hypercalciuria. The magnitude of hypercalcemia is the key consideration in determining the need for immediate and aggressive therapy. There are four main strategies for lowering serum calcium: decreasing intestinal calcium absorption; increasing urinary excretion; decreasing bone resorption; and removing excess calcium through dialysis. We report on an adolescent with thalassemia who developed severe hypercalcemia during regular clinical follow-up for hypoparathyroidism treatment with calcitriol and calcium. He was also receiving levothyroxine for primary hypothyroidism and iron chelation therapy with desferioxamine mesylate for the severe iron overload.
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PMID:Severe hypercalcemia in a patient treated for hypoparathyroidism with calcitriol. 2067 97

In the present work the effect of subcutaneous administration of 250, 500 and 750 microg (10.000, 20.000 and 30.000 IU, respectively) of vitamin D3 (calciferol) daily for eight days, on serum concentrations of vitamin D3 and 25-hydroxyvitamin D3 (25-OH-D3) and on serum and tissue concentrations of Ca, Zn, Cu and Fe in 45 white male Wistar rats, aged 12 weeks and weighing 180-200 g, have been studied. The group control was integrated by 15 healthy rats with similar characteristics (strain, gender, age and weight) that treated animals. Administration of high doses of calciferol produced a hypervitaminosis D characterized by a significant (p < 0.05) increase in serum vitamin D3 and 25-OH-D3, diverse clinical signs (such as, anorexia, marked loss of body weight, bloody diarrhea, bilateral conjunctivitis, and death), hypercalcemia, hypozincaemia, hypercupremia, hypoferraemia and an alteration in the tissue distribution of Ca, Zn, Cu and Fe as compared with untreated controls. Hypercalcemia and inflammation are prominent findings in hypervitaminosis D. Inflammation or infection induce systemic changes, collectively known as the acute phase response. Among the varied alterations that together produce this response are hypoferraemia, hypozincaemia and hypercupremia. It is likely that these responses are mediated, in part, by production and release of cytokines such as interleukin 1, interferons (IFN-alpha), interleukin 6 (11-6) and tumor necrosis factor (TNF). The development of hypoferraemia during inflammation requires hepcidin, an iron regulatory hormone, a disulfide-rich peptide, produced in the liver in response to the release of I1-6 during inflammation/infection. In conclusion, our results provide evidence that short-term administration of high doses of vitamin D determined diverse clinical signs and produced a marked increase of serum vitamin D3 and 25-OH-D3 and a marked alteration in the serum and tissue concentrations of Ca, Zn, Cu, and Fe. These changes depend on the doses given of vitamin D.
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PMID:[Clinical signs and changes in serum and tissue chemistry in rats treated with vitamin D3 (calciferol)]. 2269 92


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