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

The authors describes a case of tertiary hyperparathyroidism (HPTH) in a uremic patient on intermittent dialysis treatment: the term refers to an adenoma with ensuing uncontrolled parathormone (PTH) secretion rate arising on the ground of hyperstimulated hypertrophied parathyroid glands. The syndrome was heralded clinically by bone pain, psychiatric disorder and biochemically by increased levels of calcium and alkaline phosphatase (AP), while parathormone (PTH), did not change from basal very high levels as commonly found in uraemic patients. As hypercalcemia in the hemodialyzed is an infrequent finding the only alternative explanation could have been hypercalcemic secondary HPTH related to hyperplastic autonomous parathyroids. For no clinical and laboratory findings as well as US findings and double scintigraphy (99mTc and 201mTl) may suggest differential diagnosis the patient underwent total parathyroidectomy which actually revealed an adenoma of the left superior parathyroid gland. Bone pain and psychiatric disturbances disappeared and now get well on chronic dialysis treatment and 1.25-OH Vit D3 supplement.
 ...
PMID:[Tertiary hyperparathyroidism during chronic kidney failure under dialysis treatment. Apropos a clinical case]. 841 36

Twenty-seven patients, eighteen females and nine males, with chronic renal failure and secondary hyperparathyroidism, were treated by subtotal parathyroidectomy. Bone pain, in 24 patients, hypercalcemia in 2 and severe pruritus in 1 were the main indications to surgery. Result evaluation was possible in twenty four patients. Bone pain disappeared or was reduced in 20/22 patients. Serum alkaline phosphatase and PTH returned to normal in 21/24 patients. There patients had persistent hyperparathyroidism because of inadequate surgical exploration. Another group of seven patients with secondary hyperparathyroidism recalcitant to medical therapy or relapsing after subtotal parathyroidectomy was treated with calcitriol ev. After nine months of follow-up PTH and alkaline phosphatase serum levels were reduced to normal value in all patients.
 ...
PMID:[Hyperparathyroidism resulting from chronic renal insufficiency. Diagnosis and therapy]. 850 46

The variability of different primary tumors in the susceptibility to metastatic bone disease is poorly understood. Factors that determine the viability of metastatic cells are also poorly understood, but may depend in part upon gene expression of PTHrP and the vitamin D receptor. In contrast, much more is known of the manner in which metastatic disease affects bone remodeling to induce osteolytic bone disease. Mechanisms include a generalized increase in activation frequency at sites close to metastatic tissue, an imbalance between the amount of bone formed and that resorbed within resorption cavities, and uncoupling of bone formation from bone resorption. The greatest morbidity from metastatic bone disease arises from osteolytic disease and gives rise to hypercalcemia, bone pain, and fractures. Because osteolysis is primarily mediated by the activation of osteoclasts, there has been a great deal of interest in the use of agents which primarily affect bone metabolism to alter the natural history of metastatic bone disease. Nonsteroidal antiinflammatory agents and cytotoxic agents are capable of inducing responses in bone, but are limited by their toxicity when effective doses are utilized. The use of calcitonin in the long-term suppression of osteolysis has also been disappointing. The bisphosphonates are, however, capable of inducing sustained decreases in osteoclast activity and numbers in patients with osteolytic bone disease. There are now several studies which have examined the effects of the bisphosphonates on skeletal morbidity in breast cancer. Both clodronate and pamidronate decrease the incidence of hypercalcemia, bone pain, and pathological fractures, but do not significantly alter mortality.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Bone and cancer: pathophysiology and treatment of metastases. 857 90

Osteolytic bone destruction and its complications, bone pain, pathologic fractures, and hypercalcemia, are a major source of morbidity and mortality in patients with multiple myeloma. The bone destruction in multiple myeloma is due to increased osteoclast (OCL) activity and decreased bone formation in areas of bone adjacent to myeloma cells. The mechanisms underlying osteolysis in multiple myeloma in vivo are unclear. We used a human plasma cell leukemia cell line, ARH-77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses IgG kappa, as a model for human multiple myeloma, SCID mice were irradiated with 400 rads and mice were injected either with 10(6) ARH-77 cells intravenously (ARH-77 mice) or vehicle 24 hours after irradiation. Development of bone disease was assessed by blood ionized calcium levels, x-rays, and histology. All ARH-77, but none of control mice that survived irradiation, developed hind limb paralysis 28 to 35 days after injection and developed hypercalcemia (1.35 to 1.46 mmol/L) a mean of 5 days after becoming paraplegic. Lytic bone lesions were detected using x-rays in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Controls or ARH-77 mice, after developing hypercalcemia, were then killed and bone marrow plasma from the long bones were obtained, concentrated, and assayed for bone-resorbing activity. Bone marrow plasma from ARH-77 mice induced significant bone resorption in the fetal rat long bone resorption assay when compared with controls (percentage of total 45Ca released = 35% +/- 4% v 11% +/- 1%). Histologic examination of tissues from the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen and marked infiltration in vertebrae and long bones, with loss of bony trabeculae and increased OCL numbers. Interestingly, cultures of ARH-77 mouse bone marrow for early OCL precursors (colony-forming unit-granulocyte-macrophage [CFU-GM]) showed a threefold increase in CFU-GM from ARH-77 marrow versus controls (185 +/- 32 v 40 +/- 3 per 2 x 10(5) cell plated). Bone-resorbing human and murine cytokines such as interleukin-6 (IL-6), IL-1 alpha or beta, TGF-alpha, lymphotoxin, and TNF alpha were not significantly increased in ARH-77 mouse sera or marrow plasma, compared with control mice, although ARH-77 cells produce IL-6 and lymphotoxin in vitro. Conditioned media from ARH-77 cells induced significant bone resorption in the fetal rat long bone resorption assay when compared with untreated media (percentage of total 45Ca released = 22% +/- 2% v 11% +/- 1%). This effect was not blocked by anti-IL-6 or antilymphotoxin (percentage of total 45Ca released = 19% +/- 1% and 22% +/- 1%, respectively). Thus, we have developed a model of human multiple myeloma bone disease that should be very useful to dissect the pathogenesis of the bone destruction in multiple myeloma.
 ...
PMID:Development of an in vivo model of human multiple myeloma bone disease. 860 40

The purpose of this study was to analyse the presenting clinical and laboratory features and the outcome of 72 patients with multiple myeloma (MM) who were younger than 40 years. The records of all Mayo Clinic patients with MM younger than 40 years who were seen between 1 January 1956 and 31 December 1992 were reviewed. Survival was measured from the date when treatment was required to the date of last follow-up or death. The frequency of MM in patients younger than 40 and 30 years in 3278 Mayo Clinic patients was 2.2% and 0.3%, respectively. The main presenting clinical features were bone pain (66%), fatigue (26%), extramedullary plasmacytomas (19%) and bacterial infection (11%). Renal function impairment (creatinine level > or = 177 micromol/l) and hypercalcaemia (serum calcium value > or = 2.75 mmol/l) occurred in 29% and 30% of patients, respectively. Among the 57 patients evaluable for response the objective response rate was 54%. 14/35 patients treated with a single alkylating agent achieved an objective response, whereas 17/22 patients given combination chemotherapy had an objective response (P=0.013). However, this higher response rate did not result in a significantly longer survival. The median survival for the 72 patients was 54 months. Patients with good prognostic features (normal renal function or low beta 2-microglobulin level) had a median survival of 8 years. The actuarial survival at 5 and 10 years after initiation of therapy was 43% and 13%, respectively. In summary, survival in very young patients with myeloma is longer than that observed in series of patients of all ages, especially in those with good prognostic factors.
 ...
PMID:Presenting features and prognosis in 72 patients with multiple myeloma who were younger than 40 years. 863 27

Smouldering myeloma is a monoclonal gammopathy in which the M component is higher than 30 g/l and the proportion of plasma cells in the bone marrow is higher than 10% with no anemia, renal failure, hypercalcemia, osteolysis or other features due to the monoclonal gammopathy. The recognition of this clinical variant of myeloma resides in the fact that treatment should be deferred until there are clinical or biologic data indicating evident disease progression. Vertebral hemangioma is a relatively frequent benign tumor in the general population which, although usually asymptomatic, may cause local or radicular bone pain. A patient who fulfilled the criteria of myeloma and who complained of localized bone pain in the spinal column is herein presented. Following a study of the dorsolumbar column by computerized tomography and magnetic resonance, bone lesions with radiologic images characteristic of vertebral hemangioma, clearly different from those observed in myelomatous lesions, were identified. This finding conditioned the treatment, which included radiotherapy for the vertebral hemangioma and no treatment for the smouldering myeloma.
 ...
PMID:[Vertebral hemangioma and quiescent myeloma: association of therapeutic significance]. 868 19

Frequent complications of bone metastases include pain, pathologic fracture, hypercalcemia and spinal cord compression. Lytic bone metastases result from excessive activation of osteoclasts by tumor-produced cytokines. Aredia (pamidronate) is a potent bisphosphonate that inhibits osteoclast activation. In two dose-seeking phase I trials in patients with breast cancer and prostate cancer, repeated intravenous infusion of Aredia was shown to be safe and effective in reducing bone resorption and pain. In a randomized phase III trial of 377 patients with multiple myeloma, Aredia was administered in a dosage of 90 mg i.v. every 4 weeks. Compared with placebo, treatment with Aredia was associated with a significant decrease in bone pain and in the incidence and time to development of all skeleton-related events. Data from two phase III breast cancer trials each involving 300 patients are now being analyzed. The newer bisphosphonates can safely be used together with standard anticancer therapy to provide effective palliation of symptoms caused by lytic bone metastases.
 ...
PMID:The role of bisphosphonates in the treatment of bone metastases--the U.S. experience. 873 55

The skeleton is the most common site of metastatic disease in breast cancer and the site of first distant relapse in almost one half of the cases. Bone metastases are the source of a considerable morbidity, including pain, long bone fractures in 10-20%, and hypercalcemia in 10-15% of the cases. The median survival after first relapse in bone is close to two years compared to three months after first relapse in liver. A review of endocrine and chemotherapy trials indicates that patients with metastatic bone disease have a lower response rate to antineoplastic therapy than patients with soft tissue or visceral metastases, but this probably reflects selection bias and the insensitivity of our current methods for evaluating bone response. Classical UICC criteria require radiological recalcification, implying not only tumor regression but also bone healing, which can take many months. Symptom evaluation, measurement of tumor markers and of biochemical parameters of bone turnover should be further investigated for early assessment of bone response. Pain relief could occur in more than half of the patients after radiotherapy, but uncertainty remains as to the relationship between radiotherapy dose or fractionation and the incidence duration of pain relief. Radioactive isotopes have been used successfully in patients with blastic bone metastases from prostate cancer, but controlled studies are lacking in breast cancer. The pathophysiology of metastatic bone destruction makes it logical to use osteoclast inhibitors. Bisphosphonates are potent inhibitors of bone resorption that have opened the way for a noncytotoxic medical treatment of bone metastases. Two large-scale studies in patients with breast cancer metastatic to the skeleton, one with clodronate and one with pamidronate, indicate that the prolonged administration of oral bisphosphonates, in addition to systemic antineoplastic therapy, can reduce the frequency of morbid skeletal events, including the incidence of hypercalcemic episodes and the need for radiotherapy, and probably the incidence of severe pain and of fractures. On the other hand, in patients with established tumor-induced osteolysis, intravenous pamidronate infusions can induce bone pain relief and an objective sclerosis of lytic lesions maybe in one-third and in one-fourth of the cases, respectively. These figures must, however, be taken with caution, and prospective placebo-controlled trials in large series of patients are needed.
 ...
PMID:Clinical trials in metastatic breast cancer to bone: past--present--future. 885 20

Clinical research over the last decade has confirmed the helpful role of bisphosphonates in the management of patients with bone metastases secondary to breast cancer and other malignancies. This role is also expanding in myeloma and in the management of osteoporosis. Current clinical research in oncology is focusing on their potential for the prevention of skeletal complications of malignant disease and the development of bone metastases while basic researchers are developing compounds of higher potency and, perhaps, higher therapeutic efficacy. One of the earliest agents to be investigated, etidronate, is effective in the management of malignant hypercalcemia and, when used orally and intermittently, results in reduced bone loss in osteoporosis. However, it does not appear to reduce pain in patients with malignant disease. Clodronate has been shown to be an effective agent in the management of hypercalcemia and can be used as a single intravenous infection for this purpose. Clodronate is also effective in some patients in reducing bone pain and improving mobility. When used orally, it can, as can pamidronate, reduce the skeletal complications of breast cancer such as hypercalcemia, bone fractures and bone pain. It may have fewer gastrointestinal side effects than oral pamidronate. There is emerging evidence that bisphosphonates may delay or prevent the clinical appearance of bone metastases as well as reduce other skeletal complications. Trials of adjuvant bisphosphonates such as clodronate and pamidronate in operable breast cancer are currently under way in Europe and North America.
 ...
PMID:Role of bisphosphonates in prevention and treatment of bone metastases from breast cancer. 885 26

Sodium clodronate is effective in the management of osteolytic lesions, hypercalcaemia and bone pain associated with skeletal metastasis. Clinical and biochemical data underpin a licensed total daily dose of 1600-3200 mg.
 ...
PMID:Bioavailability of two clodronate formulations. 887 4


<< Previous 1 2 3 4 5 6 7 8 9 10