Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with primary hyperparathyroidism and multiple myeloma did not have roentgenographic evidence of either disease, yet there was biochemical evidence for both diseases. Hyperparathyroidism was diagnosed by hypercalcemia and increased parathyroid hormone values. Multiple myeloma was diagnosed by serum gamma-globulin component of 2.74 g/dL with a monoclonal spike and bone marrow plasmacytosis of 31%. The serum IgA level was 2.22 g/dL and the IgG and IgM levels were normal. Serum and urine immunoelectrophoresis showed abnormal IgA and lambda arcs. Computed tomography of the neck localized a parathyroid adenoma that was found and removed at surgery.
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PMID:Primary hyperparathyroidism complicated by multiple myeloma. 648 91

Forty-two consecutive patients with untreated myelomatosis (MM) formed the basis of settling the validity of measuring the renal plasma clearance (RPC), either indirectly using the serum creatinine or directly using the glomerular filtration rate (GFR) when studying anaemia, calcium metabolism, proteins in serum and urine, and prognosis. Patients without light chain excretion in the urine had a higher GFR (P less than 0.01) than patients with light chain excretion. The haemoglobin concentration (Hb) was strongly correlated (P less than 0.001) to both, serum creatinine and GFR. Patients with normal serum concentrations of the physiological immunoglobulins had higher Hb (P less than 0.01) than patients with reduced serum immunoglobulins. Patients with serum calcium greater than 3.00 mmol/1 had additional reduced GFR compared with the other myeloma patients. The serum parathyroid hormone was decreased (P less than 0.01) and inversely correlated to the GFR. Patients with increased serum creatinine, reduced GFR or with osteolytic bone lesions had a decreased survival rate. The study shows that the major factor in prediction of Hb and prognosis in patients with MM is the RPC expressed either as the serum creatinine or the GFR. In addition, the significant correlations between the GFR and the other variables in MM assessed the RPC to be a useful and valuable marker in studies of anaemia, protein and calcium metabolism and prognosis in MM.
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PMID:Renal plasma clearance: a valuable marker in myelomatosis. 708 63

In malignancy-associated hypercalcemia (MAH) elevated plasma calcium levels are believed to inhibit parathyroid secretion independently of the underlying tumor. This predicts that correction of hypercalcemia should disinhibit circulating parathyroid hormone (PTH) levels, irrespective of the underlying disease. We have tested this hypothesis in subjects with multiple myeloma (MM) and squamous cell carcinoma (SCC) treated with pamidronate. In the MM group, PTH levels returned to normal as hypercalcemia was corrected. In contrast, PTH levels remained low in the SCC group despite a similar fall in plasma calcium. Calcitriol levels were significantly higher and magnesium levels slightly lower in the SCC group than those in the MM group. We conclude that the parathyroid response to the correction of hypercalcemia is blunted in subjects with SCC but not MM. In addition to hypercalcemia, other factors, perhaps related to tumor secretion of PTH-related protein, may therefore contribute to suppressing PTH secretion in MAH due to SCC.
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PMID:Blunted parathyroid response to correction of hypercalcemia in subjects with squamous cell carcinoma. 811 24

The overall effects of corticosteroids on the skeleton are dependent on many factors including dose, duration of exposure to the steroid, steroid type and species. Some effects are indirect and are brought about by changes in, for example, parathyroid hormone secretion and intestinal calcium absorption, while others may result from cellular responses within the microenvironment of bone itself. Explants of trabecular bone are commonly used to study glucocorticoid effects in vitro, though it is often difficult to be certain that in vitro results directly reflect in vivo activity. Corticosteroids are dual inhibitors of cyclo-oxygenase and lipo-oxygenase, and may exert effects via inhibition of eicosanoid synthesis. They can also inhibit synthesis of cytokines, such as interleukin-1, which stimulate bone resorption and remodelling, by monocytes and macrophages. The production of cytokines and growth factors by bone cells themselves and the expression of their receptors may also be influenced by corticosteroids. Examples of corticosteroid-induced inhibition of synthesis include tumour necrosis factor and interleukin-6, and such effects may be important in explaining therapeutic actions of corticosteroids (e.g. in myeloma). Although it is not yet clear why different glucocorticoids have different effects, a number of factors determine the overall effect of a steroid. These include steroid metabolism and tissue distribution, selective effects on cytokine production, and tissue differences in gene transcription.
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PMID:Cellular regulatory mechanisms that may underlie the effects of corticosteroids on bone. 849 80

The incidence of hypercalcaemia and its association with humoral mechanisms involving parathyroid hormone-related protein (PTHrP), parathyroid hormone (PTH), or 1.25(OH)2 vitamin D were assessed in a prospective study of patients admitted to a clinical haematology unit. Hypercalcaemia was detected in 18/165 patients, and was due to primary hyperparathyroidism in 3/17 patients in whom results of humoral mediator assessments were obtained. In the other patients, hypercalcaemia was associated in nine instances with myeloma, in five with B-cell non-Hodgkin's lymphoma (NHL), and in one with myeloid neoplasia. No evidence was obtained of a humoral mechanism involving 1.25(OH)2 vitamin D, but elevated circulating levels of PTHrP, comparable with those in humoral hypercalcaemia of malignancy, were present in 2/4 patients with NHL, and in 3/9 with myeloma. The relationship between presence or absence of elevated circulating PTHrP, and presence or absence of hypercalcaemia during the course of treatment, indicated PTHrP was involved in the production of hypercalcaemia. Such an association raises the possibility that PTHrP released by neoplastic cells in these disorders acts in a paracrine manner to produce local bone resorption, and when produced in greater amounts causes elevated circulating levels which make an additional humorally-mediated contribution to the development of hypercalcaemia.
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PMID:Parathyroid hormone-related protein in hypercalcaemia associated with haematological malignancy. 913 72

Stimulation of bone resorption by local factors, the cytokines, is key to the development of hypercalcemia in multiple myeloma patients. Parathyroid hormone-related peptide, the systemic factor found in humoral hypercalcemia, has rarely been incriminated in myeloma. We report a case of myeloma with hypercalcemia and elevated serum level of parathyroid hormone-related peptide. Bisphosphonate therapy was rapidly effective in correcting serum calcium levels despite persistent high levels of the peptide. Seven other cases of myeloma with hypercalcemia and high serum parathyroid hormone-related peptide levels have been reported. Expression by myeloma plasmocytes of the messenger RNA for this peptide has also been demonstrated. These data suggest that parathyroid hormone-related peptide may contribute to the development of hypercalcemia in some myeloma patients.
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PMID:Secretion of parathyroid hormone-related peptide in patients with multiple myeloma. 889 65

Interleukin-6 (IL-6) is known to enhance osteoclast recruitment, and thereby bone resorption. Thus, IL-6 has been proposed to mediate hypercalcemia in multiple myeloma and the enhanced osteoclastic activity seen in postmenopausal osteoporosis. We recently reported that the calcium concentration in plasma affects IL-6 secretion from mononuclear blood cells. To investigate the underlying mechanism, we have studied the effect of calcium on IL-6 formation in mononuclear blood cells ex vivo and in vitro. Thirteen healthy volunteers were given 1 g of calcium orally after overnight fasting. Plasma levels of ionized calcium (pCa2+) and serum levels of parathyroid hormone (sPTH) were measured after 2 and 4 h, with all subjects still fasting. After 2 h, pCa2+ was increased and sPTH decreased in all 13 persons. IL-6 secretion ex vivo from mononuclear blood cells drawn 4 h after calcium intake was increased 185% as compared with IL-6 secretion from cells drawn just before calcium intake. In control experiments without calcium intake, there was no alteration in pCa2+ and no effect on IL-6 secretion from mononuclear blood cells. In vitro studies revealed that stimulation of isolated mononuclear blood cells with physiological concentrations of calcium dose-dependently increased IL-6 secretion with an estimated EC50 at 1.2 mM Ca2+. No effect on the IL-6 secretion was seen following treatment of the isolated mononuclear blood cells with PTH or calcitonin. These observations demonstrate that the plasma calcium concentration affects IL-6 secretion from mononuclear blood cells. The in vitro data indicate the involvement of a direct calcium sensing mechanism. These findings might have implications in hypercalcemia and should also be borne in mind when considering the role of cytokines in osteoporosis.
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PMID:Regulation of interleukin-6 secretion from mononuclear blood cells by extracellular calcium. 904 Oct 54

We report a case of 77-year-old woman who presented with lumbago and hypercalcemia. Multiple myeloma (MM) was first diagnosed by serum protein electrophoresis and bone marrow aspiration, but intact parathyroid hormone (intactPTH) was also found to be high in the presence of persistent hypercalcemia with anorexia and nausea. After lowering serum calcium with bisphosphonate administration, parathyroidectomy was performed. Upon histologic examination, the tumor was determined to be parathyroidal chief-cell hyperplasia and the patient was treated with melphalan and prednisolone. The relationship between MM and primary hyperparathyroidism (I degree HPT) remains unknown. Although the co-existence of MM and I degree HPT was reported in 12 reports from various parts of the world, there was only 1 report in Japan. The present case is an example of successful treatment for a complicated disorder, and suggests that patients suffering from bone pain or hypercalcemia need to be examined both endocrinologically and hematologically.
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PMID:A case of primary hyperparathyroidism accompanying multiple myeloma. 915 21

We examined the ultrastructure of myeloma cells producing parathyroid hormone-related peptide. The nucleus was mature and the cytoplasm was well-developed, being classified into the mature type with slight nucleo-cytoplasmic asynchrony. Although various nuclear and cytoplasmic abnormalities commonly observed in myeloma cells were recognized, a multilamellar body-like structure which has not been reported previously in myeloma cells was characteristically observed. Numerous nuclear and cytoplasmic abnormalities observed in the myeloma cells of this case were considered to have resulted from increased and aberrant proliferation of myeloma cells. We reported previously that the immature nucleus and various nuclear and cytoplasmic abnormalities are related to poor prognosis. Thus, the ultrastructural findings of myeloma cells in this case is not inconsistent with the short survival time.
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PMID:Ultrastructure of myeloma cells producing parathyroid hormone-related peptide. 921 58

We report a patient with multiple myeloma and a prolonged history of hypophosphatemia who had remained asymptomatic. Extensive evaluation for a cause, including the search for a renal tubular disorder, oncogenous osteomalacia, or a parathyroid hormone (PTH)-related protein was unproductive. Renal biopsy showed no evidence of myeloma kidney. Subsequent mixing of the immunoglobulin G (IgG) fraction from the patient's serum with normal human serum, confirmed that the observed hypophosphatemia was spurious, resulting from interference of large amounts of an abnormal IgG with a standard automated laboratory assay for phosphate.
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PMID:Spurious hypophosphatemia in a patient with multiple myeloma. 932 75


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