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)

Despite advanced techniques of renal replacement therapy the overall mortality of patients with ARF is still high. The majority of patients with ARF requiring dialysis are those with nontraumatic ARF. In a retrospective study we compared the causes of nontraumatic ARF, the risk factors for the development of renal failure and the mortality rates in patients with and without diabetes mellitus who received dialysis therapy in the years 1991-2000. A total of 232 patients were included in the study, 34 (14.6%) of them with and 198 patients (85.4%) without diabetes. The predominant causes of nontraumatic ARF like congestive heart failure (26.4 vs. 13.6, p < 0.05) and hypotension/hypovolemia (20.6 vs. 7.6%, p < 0.05) occurred more frequently in diabetic patients. The prevalence of sepsis (8.8 vs. 10.1%, NS), malignancy/ hypercalcemia (5.8 vs. 11.6%, NS) and other causes of nontraumatic ARF were similar in both groups. The prevalence of hepato-renal syndrome (5.8 vs. 13.6%, p < 0.05) and acute kidney graft failure (2.9 vs. 15.1%, p < 0.05) was higher in the nondiabetic individuals. Patients with diabetes showed more often chronic predictors for the onset of ARF like pre-existing hypertension (93.6 vs. 51.0%, p < 0.05), congestive heart failure (44.1 vs. 14.6%, p < 0.005), pre-existing renal insufficiency (76.4 vs. 46.9%, p < 0.05) and ACE-inhibitor therapy (32.3 vs. 9.6%, p < 0.005). Additionally, the prevalence of multiple organ failure (MOF) as prognostic factor was significantly higher in the diabetic patients (47.0 vs. 21.7%, p < 0.05). The mean number of dialyses therapy was 4.7 vs. 4.5 per patient. The overall mortality was 41.1 vs. 44.% (NS). In conclusion, the prevalence of the most common causes of nontraumatic ARF was different between the patients with and without diabetes. The diabetic individuals had more frequently predictors for the onset of ARF. The overall mortality was approximately the same in both groups.
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PMID:Causes and prognosis of nontraumatic acute renal failure requiring dialysis in adult patients with and without diabetes. 1508 20

Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice. INDO and INDO plus MPA treatments significantly inhibited tumor growth, which was not inhibited by MPA. The number of lung metastatic nodules was decreased with all treatments, being most effective INDO alone and INDO plus MPA. A significant decrease of plasmatic levels of the matrix metalloproteinases MMP-9 and MMP-2 correlated with these results. Paraneoplastic syndromes, leukocytosis, and cachexia were abolished by all treatments. We determined effects of the treatments on circulating cytokines shown to regulate cachexia and inflammation. Both treatments alone, and INDO plus MPA, reduced circulating IL-6 throughout tumor evolution. A pronounced increase in serum IL-1ss levels was detected in untreated tumor bearers. These levels decreased and were closer to normal serum values when LP07 mice were treated with INDO plus MPA. The combination of a nonsteroidal antiinflammatory drug as INDO and MPA showed to be effective in inhibiting tumor and metastatic growth and diminishing paraneoplastic symptoms and SIR. A variety of specific molecules are implicated as playing a role in cancer-induced cachexia and hematological alterations.
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PMID:Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin. 1653 80

Abnormal bone in chronic kidney disease (CKD) may adversely affect vascular calcification via disordered calcium and phosphate metabolism. In this context, bone health should be viewed as a prerequisite for the successful prevention/treatment of vascular calcification (VC) along with controlled parathyroid hormone (PTH) secretion, the use of calcium-based phosphate binders and vitamin D therapy. In CKD patients, VC occurs more frequently and progresses more rapidly than in the general population, and is associated with increased cardiovascular disease (CVD) morbidity and mortality. A number of therapies aimed at reducing PTH concentration are associated with an increase of calcaemia and Ca x P product, e.g. calcium-containing phosphate binders or active vitamin D. The introduction of calcium-free phosphate binders has reduced calcium load, attenuating VC and improving trabecular bone content. In addition, a major breakthrough has been achieved through the use of calcimimetics, as first agents which lower PTH without increasing the concentrations of serum calcium and phosphate. Nowadays, it is becoming evident that even early stage CKD is recognised as an independent CVD risk factor. Moreover, the excess of CVD among dialysis patients cannot be explained entirely on the basis of abnormal mineral and bone metabolism. Hence, much controversy has surrounded the cost-effectiveness of treatment with the new phosphate-binding drugs as well as new vitamin D analogs and calcimimetics. Thus, it seems prudent and reasonable that maintaining bone health and mineral homeostasis should rely on some modifications of standard phosphate binding and calcitriol therapy. Hypophosphataemia and hypercalcaemia in adynamic bone disease (ABD) might be treated by reducing the number of calcium carbonate/acetate tablets in order to increase serum phosphate and decrease serum calcium, which, in turn, might positively stimulate PTH secretion. The same rationale is assumed for the use of a low calcium dialysate. On the other hand, secondary hyperparathyroidism with hyperphosphataemia and hypocalcaemia should be treated with a substantial number of calcium carbonate/acetate tablets in combination with calcitriol and low calcium dialysate in order to decrease serum phosphate and maintain the Ca x P product within K/DOQI guidelines (<4.4 mmol l(-1)). Finally, it becomes apparent that prevention, with judicious use of calcium-based binders, vitamin D and a low calcium dialysate without adverse effects on Ca x P or oversuppression of PTH, provides the best management of VC and mineral and bone disorder in CKD patients.
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PMID:Bone health and vascular calcification relationships in chronic kidney disease. 1789 31

The abnormalities in bone and mineral metabolism in chronic kidney disease patients are associated with an increased risk of fractures, vascular calcifications and cardiovascular diseases. A few decades ago hyperphosphatemia and the common development of secondary hyperparathyroidism were thought to be the main problem to deal with. Since dietary phosphate restriction and haemodialysis were not proven to be sufficient measures to reduce phosphorus, phosphate-binding therapy has been widely instituted as a treatment option. Various types of phosphate binders employed over the years have contributed to the changing spectrum of renal osteodystrophy from high to low bone turnover along with the shift from hypocalcemia and negative calcium balance towards hypercalcemia and the positive calcium balance. Thus, hypercalcemia instead of hyperphosphatemia is nowadays associated with the increased risk of vascular calcification, morbidity and mortality in the dialysis population. Besides the very expensive non-calcium based phosphate binders, at least two common tools may be helpful in the treatment of hypercalcemia and adynamic bone. A reduced daily use of calcium carbonate/acetate up to 1g per main meal is an easily manageable and inexpensive tool. The second option for stimulation of parathyroid gland activity and bone turnover is the lowering of the dialysate calcium concentration. In conclusion, an aggressive treatment of hyperphosphatemia and calcium overload might lead towards an opposite effect of hypoparathyroidism and hypercalcemia. Reasonable treatment strategies based on a careful monitoring should be employed in order to prevent related consequences and to contribute to a better long-term quality of life and survival of dialysis patients.
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PMID:New aspects of treatment of renal bone disease in dialysis patients. 1793 68

A 62-year-old man visited our hospital complaining of asymptomatic gross hematuria. Right radical Computed tomography (CT) demonstrated an 8 cm mass in the right kidney. nephrectomy was done in March 1995, and the pathological examination revealed renal cell carcinoma (RCC), clear cell type, G2>G1. Interferon (IFN)-alpha was administered for 10 months. About 3 years later, in March 1998, CT showed 1 cm mass in the left kidney. Left partial nephrectomy was done and the pathological finding was RCC, G1. IFN-alpha2b was administered for a year. About 2 years later, CT showed 2.7 cm mass in the left lung. Left upper lobectomy was performed in August 2000, and it was a metastasis of RCC, G2. IFN-alpha and IFN-gamma were administered. Nine months later, in June 2001, the recurrence of the left kidney and the left adrenal gland was found and partial nephrectomy and adrenalectomy was performed. Pathological finding was RCC, G3. IFN-alpha and tegafur-uracil (UFT) were administered. Only 3 months later, recurrence of the left kidney and the left adrenal gland and the lymph node of renal hilus was found. We gave up for surgical resection and chemotherapy of MVP (Methotrexate, Vinblastine, Pepleomycin) was performed. Despite the therapy, disease progressed. 10 months after the last recurrence, in July 2002, patient became disoriented and hypercalcemia and the MVP therapy was stopped. After that, medroxyprogesterone acetate (MPA) and UFT were administered; the patient lived 20 months with relatively good performance status and died in February 2004. MPA might be considered as a drug for advanced renal cell carcinoma.
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PMID:[A case of recurrent renal cell carcinoma which recurred after fourth surgical resection and survived for about 2 years by medroxyporgesterone acetate administration]. 1793 37

1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a vitamin D receptor (VDR) ligand, regulates calcium homeostasis and also exhibits noncalcemic actions on immunity and cell differentiation. In addition to disorders of bone and calcium metabolism, VDR ligands are potential therapeutic agents in the treatment of immune disorders, microbial infections, and malignancies. Hypercalcemia, the major adverse effect of vitamin D(3) derivatives, limits their clinical application. The secondary bile acid lithocholic acid (LCA) is an additional physiological ligand for VDR, and its synthetic derivative, LCA acetate, is a potent VDR agonist. In this study, we found that an additional derivative, LCA propionate, is a more selective VDR activator than LCA acetate. LCA acetate and LCA propionate induced the expression of the calcium channel transient receptor potential vanilloid type 6 (TRPV6) as effectively as that of 1alpha,25-dihydroxyvitamin D(3) 24-hydroxylase (CYP24A1), whereas 1,25(OH)(2)D(3) was more effective on TRPV6 than on CYP24A1 in intestinal cells. In vivo experiments showed that LCA acetate and LCA propionate effectively induced tissue VDR activation without causing hypercalcemia. These bile acid derivatives have the ability to function as selective VDR modulators.
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PMID:Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia. 1818 Feb 67

Lanthanum is an element belonging to the group called rare earths. Due to its low solubility, lanthanum carbonate has been widely studied as an intestinal phosphate binder. The results of different clinical trials show that it is an effective and well-tolerated phosphate binder used in monotherapy. Serum phosphate levels are controlled in approximately 70% of patients at 5 years without causing hypercalcemia. The only significant adverse effects observed are a low percentage of gastrointestinal disturbances (6%). Lanthanum carbonate does not alter serum values of liposoluble vitamins or affect the pharmacokinetics of digoxin, warfarin, furosemide, phenytoin, ACE inhibitors or beta-blockers. However, it does alter the pharmacokinetics of ciprofloxacin (quinolones in general), tetracyclines and doxycycline. Lanthanum carbonate (Fosrenol) is available in Spain as 500 mg, 750 mg, and 1,000 mg chewable tablets, which should not be swallowed without chewing to avoid loss of efficacy. The initial dose recommended by the WHO is 2,250 mg/day, which is equivalent to one 750 mg at each meal. Lanthanum carbonate or lanthanum phosphate can be clearly visualized on a plain x-ray of the abdomen in patients who have recently ingested it. In summary, lanthanum carbonate is a widely studied potent phosphate binder, which offers the possibility of improving control of serum phosphate in patients with chronic kidney disease, without significant side effects. The fact that it is available as chewable tablets and that the number of daily tablets required has been significantly reduced will probably facilitate better patient compliance.
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PMID:[Lanthanum carbonate in clinical practice]. 1884 14

Chronic uremia is characterized by decreased levels of plasma 1,25(OH)2D3 due to decreased renal 1-hydroxylase activity and by decreased renal phosphate excretion. The consequence is an increased synthesis and secretion of parathyroid hormone--secondary hyperparathyroidism--due to the low levels of plasma calcium, low levels of plasma 1,25(OH)2D3 and high levels of phosphate. The association between renal bone disease and chronic renal failure is well described. Epidemiological studies have indicated that an association also exists between secondary hyperparathyroidism and increased mortality and cardiovascular calcifications in chronic uremic patients. Treatment of secondary hyperparathyroidism in chronic uremia focuses on avoiding hyperphosphatemia by the use of oral phosphate binders, which bind phosphate in the intestine and a concomitant substitution by a 1 alpha-hydroxylated vitamin D analog in order to compensate for the reduced renal hydroxylation. Additional treatment with aluminum containing phosphate binders to overcome phosphate absorption and retention was initiated already in the 1960s and used extensively until aluminum toxicity was disclosed in the mid-1980s. Instead calcium carbonate and calcium acetate were used as phosphate binders. Until recently, the most commonly used active vitamin D drug was either the natural 1,25(OH)2D3, or the 1 alpha-hydroxylated analog, 1alpha(OH)D3 which after 25-hydroxylation in the liver is converted to 1,25(OH)2D3. 1alpha(OH)D3 was produced by LEO Pharma in 1973. The two vitamin D analogs were used in different geographical areas: In Europe 1alpha(OH)D3 was mainly used, while 1,25(OH)2D3 was mainly used in the USA. 1,25(OH)2D3 increases the intestinal absorption of calcium and improves skeletal abnormalities. The combined treatment with calcium containing phosphate binders and active vitamin D induces an increase in plasma Ca 2+ and hypercalcemia became a clinical problem. Subsequently therefore, dialysis fluid with a reduced calcium concentration ("low-calcium") was introduced. In 1981 Madsen et al. [148] demonstrated for the first time a direct suppressive effect of intravenous 1,25(OH)2D3 on plasma PTH in acutely uremic patients. In 1984, Slatopolsky et al. [74] demonstrated that intravenous 1,25(OH)2D3 induces a marked suppression of plasma PTH with no increase in plasma Ca 2+ in chronic uremic patients. In the middle of the 1980s, 1alpha(OH)D3 became available not only as an oral, but also as an intravenous formulation. The main purpose of the present studies was to increase the knowledge of the action and effects of different treatment regimes with 1alpha(OH)D3, and thereby to improve the prophylaxis and treatment of secondary hyperparathyroidism in uremic patients on chronic dialysis. 168 patients on chronic dialysis treatment and six healthy volunteers were included in the seven studies included in this thesis. The first part of the studies, focused on short- (12 weeks) and long-term (103 weeks) effects of intravenous 1alpha(OH)D3 on plasma PTH and plasma Ca 2+ in relation to the doses of 1alpha(OH)D3 given. Further, it was examined whether the marked suppression of plasma PTH induced by 300 days of intermittent intravenous treatment with 1alpha(OH)D3, could be maintained when the administration was changed from intravenous to the oral route for 16 further weeks and then shifted back to intravenous administration for another 16 weeks. The second part focused on long-term effects (88 weeks in hemodialysis patients and 52 weeks in CAPD patients) of a treatment modality combining 1alpha(OH)D3, and CaCO3 as phosphate binders instead of aluminum containing compounds and a decreased calcium concentration in the dialysis fluid to 1.25 mmol/l in an attempt to avoid development of hypercalcemia. The third part focused upon the pharmacokinetic differences between intravenous and oral administration of 1,25(OH)2D3 and 1alpha(OH)D3 and upon the acute effects of different doses of the two compounds on the plasma levels of PTH, Ca 2+ and phosphate. Plasma PTH is a biochemical parameter most often used for the diagnosis and monitoring of bone disease in patients with chronic uremia. The level of plasma PTH measures depends on the assay used. More specific assays measuring only whole PTH 1-84 without co-measuring large C-terminal fragments have been developed. In this thesis, five different assays were used - one "N-terminal", one "C-terminal", two "Intact" and one "Whole" PTH assay. Each sample was analyzed by 1-3 different assays. Based on the results of my studies [1-7], it is concluded that: 1a. Intravenous administration of 1alpha(OH)D3 induces a marked suppression of plasma PTH without causing serious side-effects in patients on chronic hemodialysis. It is possible to prevent hypercalcemia by closely monitoring plasma Ca 2+ levels and by adjusting the dose of 1alpha(OH)D3 accordingly. 1b. Long-term intermittent intravenous treatment with 1alpha(OH)D3 was effective in suppressing plasma levels of Intact PTH. 1c. When plasma intact PTH was suppressed to a stable level by intravenous 1alpha(OH)D3 the suppression could be maintained by intermittent oral 1alpha(OH)D3 therapy. It was not examined whether a similar degree of suppression of severe secondary hyperparathyroidism could be induced by intermittent oral 1alpha(OH)D3 treatment alone. The responses following chronic intravenous or oral administration of 1alpha(OH)D3 on circulating levels of intact PTH and N- and C-terminal PTH fragments did not reveal any significant differences between the two routes of administration on the actions on the parathyroid glands. 2a. The combination of "low-calcium" hemodialysis fluid (1.25 mmol/l), CaCO3 as a phosphate binder, and intermittent intravenous 1alpha(OH)D3 prevented development of secondary hyperparathyroidism in uremic patients with normal PTH at the initiation of the study and induced a long-term suppression of PTH in patients with secondary hyperparathyroidism. No clinical or biochemical indications of development of adynamic bone disease were observed. Intravenous administration of 1alpha(OH)D3 prevented a decrease of BMC in the lumbar spine and femoral neck of hemodialysis patients both with normal and with elevated PTH levels. It was possible to use larger doses of CaCO3 and to reduce, but not exclude, the use of aluminum-containing phosphate binders in combination with intravenous administration of 1alpha(OH)D3. A decrease of plasma Ca 2+ was induced during dialysis, and special care had to be taken on the compliance of the patients as to the use of CaCO3 binders in order not to aggravate secondary hyperparathyroidism. 2b. In patients on CAPD, the use of low-calcium dialysis (1.25 mmol/l) made it possible to use larger doses of CaCO3 phosphate binders and to reduce, but not exclude, the use of aluminium containing phosphate binder in combination with oral pulses of 1alpha(OH)D3. A negative calcium balance was induced, and it is therefore recommended that a reduction of the calcium concentration in the dialysis fluid is only used in patients under strict control. 3a. The metabolic clearance rate of 1,25(OH)2D3 was 57% lower in uremic patients than in normal subjects (p < 0.03). The bioavailability of 1,25(OH)2D3 in both normal subjects and uremic patients was markedly lower following administration of 1alpha(OH)D3 both intravenously and orally than after administration of oral 1,25(OH)2D3. Despite lower plasma 1,25(OH)2D3 levels after administration of 1alpha(OH)D3 than after 1,25(OH)2D3, no significant difference was observed in the PTH suppressive effect in uremic patients of 4 mug intravenously of either of the two vitamin D analogs. 3b. A single intravenous high dose of 10 mug of 1alpha(OH)D3 or 1,25(OH)2D3 significantly suppressed plasma PTH. The acute suppressive effect of 1,25(OH)2D3 was three times greater than that of 1alpha(OH)D3.The increase in plasma Ca 2+ after intravenous administration of 10 mug 1,25(OH)2D3 was significantly higher than that of 1alpha(OH)D3. Due to the simultaneous effect on plasma Ca 2+ observed it was not possible to decide whether 1alpha(OH)D3 has a direct effect per se on the parathyroid glands or not. The study further did not give any further knowledge about the possible therapeutic equivalence of long-term treatment with 1alpha(OH)D3 or 1,25(OH)2D3. The PTH responses to acute administration of the 1alpha(OH)D3 and 1,25(OH)2D3 analogs were in principle the same when measured by one "whole" PTH and two "intact" PTH assays, namely mainly in a parallel shift of the PTH response curve. In this study on chronic uremic patients circulating levels of large C-terminal PTH fragments were not affected by differences in plasma Ca 2+ concentration or by the intravenous administration of 1alpha(OH)D3 or 1,25(OH)2D3. There is now a general agreement on the importance of carefully controlling plasma phosphate, normalize and avoid increases of plasma Ca 2+, and not to oversuppress PTH during treatment. Focus today is on the potential deleterious role of calcium overloading in the development of vascular calcifications in uremic patients. There is an urgent need for a development of an algorithm for the use of phosphate binders and vitamin D supplementation in combination with calcimimetics focusing upon long term morbidity and mortality in uremic patients.
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PMID:1alpha(OH)D3 One-alpha-hydroxy-cholecalciferol--an active vitamin D analog. Clinical studies on prophylaxis and treatment of secondary hyperparathyroidism in uremic patients on chronic dialysis. 1923 59

We present a highly unusual and interesting case of coexistent hyperparathyroidism and sarcoidosis leading to hypercalcaemia. A 70 year old female presented with weight loss, constipation and dehydration. Investigations revealed marked hypercalcaemia with a non-suppressed PTH. In view of the degree of hypercalcaemia as well as the unintentional weight loss, investigations for malignancy were conducted -these were negative. Parathyroid imaging was then requested and an adenoma was identified. Surprisingly, surgery revealed the coexistence of a parathyroid adenoma with the unexpected finding of sarcoid granulomas within the parathyroid and thyroid glands. To our knowledge, this is the first such case reported. Further imaging confirmed pulmonary sarcoidosis and a serum ACE was elevated. Serum calcium levels did not respond to parathyroidectomy but eventually fell with steroid therapy.
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PMID:Sarcoid granulomas in the parathyroid gland - a case of dual pathology: hypercalcaemia due to a parathyroid adenoma and coexistent sarcoidosis with granulomas located within the parathyroid adenoma and thyroid gland. 2055 94

The antitumor effects of 22-oxa-1,25-dihydroxy-vitamin D-3 (OCT), a vitamin D-3 analogue, were evaluated on 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors. The combined effects of OCT (0.3 mu g/kg) with tamoxifen (0.5 mg/kg) medroxyprogesterone acetate (MPA) 2.5 mg/kg), or a new aromatase inhibitor, CGS 16949A (0.8 mg/kg) were also evaluated. OCT significantly suppressed the growth of tumors without hypercalcemia in a dose dependent manner at the fourth week from the start of treatment. Tumor size in the OCT+CGS 16949A group was significantly decreased compared with that in the OCT or CGS 16949A alone. However, there was no significant difference in tumor size between OCT alone and combined therapy with tamoxifen or MPA. We conclude that a single administration of OCT, which does not cause hypercalcemia, is effective for breast cancer and that a combination of OCT and aromatase inhibitor, CGS 16949A augments the antitumor effect on tumors compared to each single agent.
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PMID:Usefulness of 22-oxa-1,25-dihydroxyvitamin D-3 (OCT) as a single agent or combined therapy with aromatase inhibitor (CGS 16949A) on 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors. 2154 84


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