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)

There is increasing evidence regarding the importance of osteoclast activation in the pathogenesis of bone metastases. Cancer cells produce osteoclast-activating factors which play an important role in the development of bone metastases. Bisphosphonates are drugs that inhibit bone turnover by decreasing bone resorption. In patients with bone metastases from breast cancer, the effectiveness of bisphosphonate is well established for reducing skeletal complications, such as bone pain, pathological fracture, bone surgery and hypercalcemia. Recent attention has focused on a possible preventive effect on bisphosphonates of bone metastases. Animal models have supported the prevention of bone metastasis by bishosphonate therapy, but three major adjuvant clinical trials of the oral bisphosphonate clodronate have yielded conflicting results. However, our preliminary trial of intravenous bisphosphonate with pamidronate showed effective inhibition of bone metastases. Use of bisphosphonates as adjuvant therapy is still investigational yet promising. Several more randomized trials are underway to further investigate adjuvant therapy with bisphosphonates.
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PMID:Prevention of bone metastases from breast cancer by adjuvant bisphosphonate therapy. 1252 61

Multiple myeloma (MM) is a plasma cell malignancy characterized by infiltration of bone marrow, bone destruction, infiltration of soft tissues with plasma cells, and suppression of normal hematopoiesis. The production of monoclonal immunoglobulins with or without light chains is a major feature of the disease. Full spectrum of plasma cell dyscrasias include monoclonal gammapathy of undetermined significance, smouldering myeloma, indolent multiple myeloma, and fully developed, symptomatic multiple myeloma. The usual presenting features of MM include bone pain, weakness, fatigue, fever and infection. Neurologic symptoms are less common but one must not forget that MM may present with a neurologic disease. Careful neurologic history and examination are mandatory in patients with MM. Neurologic symptoms may be a direct manifestation of MM or may be due to the immune effect of monoclonal proteins directed against different neural structures. Finally, metabolic consequences (uremia, hypercalcemia, hyperviscosity) of MM may produce a broad spectrum of different neurologic symptoms including headache, blurring of vision, drowsiness, precoma, coma, vertigo, ataxia, hemiparesis and epileptiform seizures. The most common location of bone changes in MM is the thoracic spine, where it causes osteolytic changes with consequent compressive fractures. The most disastrous sequel is paraplegia. Multiple vertebral involvement with the evidence of osteolytic changes in other bones is usual, but solitary vertebral myeloma may occur. Myeloma usually involves the bone of the vertebral body and then spreads into the extradural space. However, patients with solitary extradural myeloma have been reported. Skull myeloma is frequently asymptomatic. It may grow externally or, rarely, there is intracranial expansion. Involvement of the cranial nerves is not rare, with II, V, VI, VII and VIII cranial nerves being most often affected. Isolated intracerebral plasmacytomas are extremely rare. Diagnostic approach includes plain X-rays of the skeleton, which was found to be the method of choice for demonstration of osteolytic changes, whereas magnetic resonance with gadolinium enhancement most reliably displays the degree of vertebral involvement and demonstrates any associated soft tissue mass. Current treatment of osteolytic changes in multiple myeloma include chemotherapy, radiotherapy in combination with dexamethasone, monthly infusions of bisphosphonates, surgical decompression, and kyphoplasty. Therapeutic approach is dictated by the presenting symptoms. In case of pain as the predominant symptom, treatment with chemotherapy and radiotherapy may be appropriate. Compressive symptoms are relieved with dexamethasone followed by radiotherapy and chemotherapy. Surgical decompression is used in patients with vertebral collapse and vertebral instability. Kyphoplasty is a new method used in the treatment of osteolytic changes of vertebral bodies. A viscous cement is injected into the cavity by a balloon-like inflatable bone tampon. It has been successfully employed to improve the quality of life, to reduce pain, and to increase overall functioning in patients with vertebral compression fractures by restoring most of the original height of the vertebral body. Bisphosphonates reduce pain associated with osteolytic changes in multiple myeloma, but also significantly reduce skeletal events (pathologic fracture, spinal cord compression, surgery or irradiation of bone) via unknown mechanism. It seems that bisphosphonates, by inhibiting bone resorption, alter the microenvironment in which the MM cells grow.
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PMID:[Neurologic sequelae of bone changes in multiple myeloma and its therapy]. 1263 Mar 41

With recent advances in the management of cancer, the clinical course of patients with metastatic bone disease is more likely to be prolonged and accompanied by morbidity, including severe pain, hypercalcemia, pathologic fracture, and spinal cord and/or nerve root compression. The early identification of patients at higher risk for developing bone metastases enables practitioners to be proactive in their diagnosis and treatment. A multidisciplinary approach that integrates the diagnosis and treatment of the cancer, symptom management, and rehabilitation ensures optimal care. Bisphosphonates can reduce the number of skeletal-related complications, delay the onset of progressive disease in bone, and relieve metastatic bone pain caused by a variety of solid tumors with a resulting enhanced quality of life. The complexity of the clinical problem and the need to involve an array of health-care providers present a logistical and clinical challenge. A strong argument is made for a thematically integrated bone metastases program as part of the primary care of patients with cancer.
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PMID:The multidisciplinary approach to bone metastases. 1284 27

Breast cancer (BC) is quite often accompanied by affection of the bones and alterations in mineral metabolism. The most important clinical manifestations of the above processes that appeared to a considerable extent to be a cause of a poor condition of patients include pains in bones, pathological fracture and hypercalcemia. Metastatic events in the skeleton bone are recordable in 13.5 to 85 percent of cases, as evidenced by autopsy findings. In BC patients presenting with hormone-dependent tumours and metastases in the bones, indices for survival tend to be much higher than in those patients with solid tumours of other localization. The higher level of survival in such patients warrants an effective palliative treatment to be instituted to improve quality of their lives.
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PMID:[Bone metastasis in patients with breast cancer]. 1288 49

A 4-year-old castrated male dog was evaluated because of multiple-limb lameness. Signs of pain were elicited during palpation of the regions of the proximal tibial metaphyses and distal left radial diaphysis. Radiography revealed osteolytic lesions of the long bones. Blood analyses revealed hypercalcemia and transient cytopenias. Serum protein electrophoresis did not reveal a monoclonal gammopathy; however, urine protein electrophoresis revealed Bence Jones proteinuria. Serial diagnostic sampling of bone lesions, immunohistochemical staining methods, and serum and urine protein immunoelectrophoresis were required to establish a diagnosis of multiple myeloma. Two IgM components were identified via serum protein immunoelectrofixation. The dog improved clinically after initiation of chemotherapy with melphalan and prednisone; however, the dog ultimately was euthanatized because of pathologic fracture. The case was unique because there was lack of vertebral involvement, an unusual gammopathy, and difficulty in identifying myeloma cells via serial sampling.
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PMID:Unusual IgM-secreting multiple myeloma in a dog. 1473 55

A 63-year-old woman was found to have pathological fracture of the right lower tibia through a brown tumour, hypercalcemia, and a soft tissue mass at the lower pole of the right lobe of thyroid gland. US scan of the neck showed a well-circumscribed heterogeneously-hypoechoic mass with displacement of the right lobe of thyroid gland. Diagnosis of parathyroid adenoma was confirmed on histopathological examination of the excised specimen. The cause and clinical manifestations of primary hyperparathyroidism are discussed. Imaging methods of parathyroid gland are presented.
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PMID:Clinics in diagnostic imaging (93). 1497 82

The results of a retrospective exploratory analysis of a phase III trial of zoledronic acid in patients with bone metastases secondary to lung cancer or other solid tumors are reported herein to assess the risk of skeletal-related events (SREs) and the efficacy of 4 mg zoledronic acid compared with placebo. The study is based on patient SRE history before study entry. Patients were stratified based on SRE history (eg, pathologic fracture, spinal cord compression, radiation therapy or surgery to bone, or hypercalcemia) before study entry, and SRE incidence over 21 months was analyzed. Of 507 patients randomized to 4 mg zoledronic acid or placebo, 131 completed the 9-month core phase and 69 entered the 12-month extension phase. Before study entry, 347 of 503 patients who were evaluable for efficacy (69%) experienced >/= 1 SRE; these patients had a higher risk of developing an SRE on study than patients with no prior SRE (odds ratio, 1.41). Among patients with an SRE before study entry, zoledronic acid reduced the risk of SREs by 31% (P = 0.009), reduced the mean skeletal morbidity rate (1.96 vs. 2.81 SREs per year for placebo; P = 0.030), and prolonged the median time to first SRE by nearly 4 months (215 days vs. 106 days for placebo; P = 0.011). Among patients with no SRE before study entry (n = 156), zoledronic acid reduced the risk of SREs by 23% (P = 0.308), reduced the mean skeletal morbidity rate (1.34 vs. 2.53 SREs per year for placebo; P = 0.332), and prolonged the median time to first SRE by 2.5 months (P = 0.534). This exploratory analysis demonstrates that patients with a history of SREs are at high risk for subsequent SREs, but zoledronic acid reduces skeletal morbidity regardless of SRE history.
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PMID:Clinical benefit of zoledronic acid in patients with lung cancer and other solid tumors: analysis based on history of skeletal complications. 1555 18

Multiple myeloma is a systemic malignant disease and is associated with a poor prognosis. It is characterized by neoplastic proliferation of plasma cells involved in the production and secretion of monoclonal immunoglobulins (M proteins). It is generally a disseminated disease involving many bones. Systemic symptoms include bone pain, pathologic fracture, renal failure, hypercalcemia, weight loss, anemia, thrombocytopenia, and neutropenia. This condition may occur as a solitary lesion (solitary plasmacytoma), which in some patients eventually progresses to plasma cell myeloma. Extramedullary plasmacytoma is defined as neoplastic proliferation of plasma cells in the soft tissue. It usually occurs in the upper respiratory tract, such as the nasal cavity or posterior oropharynx. The authors present a rare plasmacytoma case with maxilla involvement.
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PMID:Plasmacytoma of the hard palate. 1569 68

Breast cancer is the leading type of cancer among women, and bone metastases are common in patients with breast cancer, affecting more than half of all patients with advanced disease. Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletal-related event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and hypercalcaemia of malignancy. Bisphosphonates significantly reduced the incidence of these events. Zoledronic acid, pamidronate, clodronate and ibandronate have demonstrated efficacy compared with placebo. Zoledronic acid has also been compared with another active bisphosphonate (i.e. pamidronate) and shown by multiple event analysis to be significantly more effective at reducing the risk of SREs. Bisphosphonates effectively reduce and prevent skeletal complications in patients with bone metastases from breast cancer. Preclinical data suggest that bisphosphonates have antitumour effects. Bisphosphonates may also be of use in the adjuvant setting.
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PMID:Bisphosphonates in breast cancer. 1580 76

A 81-year-old man suffered, without any preceding trauma, from progressive pain of his left shoulder since 3 weeks. The left upper arm was warm and swollen with a palpable solid mass. Mild normocytic anemia and an increased erythrocyte sedimentation reaction were determined. X-ray showed an osteolytic lesion of left humerus with pathological fracture and involvement of soft tissue. Multiple myeloma was diagnosed from the biopsy of this lesion, detection of paraprotein IgA Kappa in the serum, and a 15-20% plasma cell infiltration of the bone marrow. The patient responded well to radio-therapy and intravenous application of biphosphonates--the fracture healed by conservative therapy. The treating physician--on the basis of clinical experience and by intuition--has to decide considering medical history and clinical findings whether musculoskeletal pain must be investigated further. Diagnosis of multiple myeloma requires monoclonal protein (paraprotein) in the serum or urine, plasma cell infiltration of the bone marrow, and evidence of end-organ damage (anemia, renal insufficiency, bone lesions or hypercalcemia).
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PMID:[Painful shoulder in the elderly--not always of degenerative nature]. 1633 10


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