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 52-year-old man was admitted to our hospital because of oliguric renal failure. The patient was well until four weeks earlier, when he developed nausea and anorexia. The urea nitrogen was 179 mg/dl, creatinine 29.2 mg/dl, uric acid 19.0 mg/dl and potassium 8.6 mEq/1. Hemodialysis was started immediately after admission. Bone marrow aspiration showed atypical plasma cell infiltration consistent with multiple myeloma. The immunoelectrophoresis revealed urinary lambda -type Bence Jones protein and serum IgD- lambda -type M protein. The findings of renal biopsy study were consistent with myeloma kidney. On the fourth hospital day, administration of prednisolone 40 mg and melphalan 2 mg was started. The patient also underwent double filtration plasma-pheresis (DFPP). Serum IgD level was decreased from 950 to 113 mg/dl. After a course of chemotherapy, however, he developed severe leukopenia and was complicated with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This complication was successfully treated with imipenem/cilastation and vancomycin combined with granulocyte colony stimulating factor (G-CSF). The patient was discharged and returned to work on maintenance hemodialysis. Fifteen months after the presentation, he manifested progressive peripheral nerve disturbances. Three months later, the patient died--not from renal failure, but from ventricular arrhythmia. The application of maintenance dialysis therapy to myelomatosis has until now been questioned. The present case, however, suggests that aggressive treatment consisting of chronic dialysis therapy as well as chemotherapy and plasma exchange should be administered even in patients with established renal failure.
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PMID:[Maintenance hemodialysis in IgD- lambda -type multiple myeloma associated with severe renal failure]. 813 51

The median duration of survival for patients with multiple myeloma ranges from 2.5 to 3 years. However, there is considerable variability from one patient to another. Renal function as determined from blood urea nitrogen or serum creatinine values, hemoglobin value, calcium level and performance status have been recognized as prognostic factors for more than 20 years. A study of 107 patients with newly diagnosed multiple myeloma at the Mayo Clinic showed that plasma cell labeling index (PCLI); levels of thymidine kinase, beta 2-microglobulin (beta 2-M), serum albumin, and C-reactive protein; and age were all significant univariate prognostic factors. Only PCLI and beta 2-M levels had independent prognostic significance. Among nine patients younger than 65 years with low PCLI and low beta 2-M levels, eight were alive almost six years after starting chemotherapy. Interleukin 6 (IL-6) is a significant univariate predictor of survival in myeloma. An elevated lactate dehydrogenase content is associated with a poor prognosis. An elevated soluble IL-6 receptor (sIL-6R) level is an independent factor associated with shorter survival. In one study, the addition of sIL-6R to PCLI and beta 2-M to the analysis doubled the proportion of patients identified as high-risk. In this study, the two-year survival was 41% at two years if the PCLI was > or = 2%, beta 2-M was > or = 4.0 micrograms/dl, or sIL-6R was > 300 ng/ml. When none of these three factors were increased, the estimated two-year survival was 83%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic factors in multiple myeloma. 852 May 13

Renal involvement known as a myeloma kidney is often observed in patients with multiple myeloma (MM). This complication has been recognized as one of the most important prognostic factors in this disease. Serum beta 2-microglobulin (S beta 2-m) has been also recognized one of the prognostic factor that reflects both a glomerular infiltration rate and a volume of neoplastic cells, because beta 2-m usually can be produced by the neoplastic lymphoid cells. To clarify the significance of the S beta 2-m in MM, we compared S beta 2-m levels and the clinical stage, with another clinical parameters for renal function such as 24 hr creatinine clearance (24 hr Ccr), N-acetyl-beta-glucosaminidase (NAG) levels in urine and serum alpha 1-microglobulin (S alpha 1-m) levels. The elevated S beta 2-m levels were commonly observed not only in patients with stage IIIB, but also in stage IA, IIA and IIIA (76%) who have normal renal function judged by the serum nitrogen or creatine levels. S beta 2-m levels correlated with 24 hr Ccr the most, then correlated with S alpha 1-m levels and less correlated with NAG levels in urine. Although a single elevation of S beta 2-m levels with other normal findings of renal parameters was found only in three out of 30 MM patients, the S beta 2-m levels in these patients did not change after the chemotherapy which had led to the diminution of serum M-protein. Together with these results, it was suggested that the S beta 2-m levels mainly reflect the renal dysfunction even if it stays in the subclinical stage, and reflect less the number of neoplastic cells in MM patients.
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PMID:[A study of the significance of serum beta 2-microglobulin levels in patients with multiple myeloma--analyzes as a marker of renal dysfunction and as a marker of tumor cell mass]. 872 43

Among plasma cell disorders, solitary plasmacytoma (solitary plasmacytoma of bone, SPB and extramedullary plasmacytoma, EMP) is rare as compared with multiple myeloma (MM). Furthermore, the relationship between solitary plasmacytoma and MM remains unclear. Between 1960 and 1994, 24 patients with SPB and 20 with EMP were treated. The criteria for diagnosis were: (1) no evidence of other lesions based on clinical and radiologic examinations; (2) biopsy evidence of a plasma cell neoplasm; (3) bone marrow biopsy specimen with negative findings (less than 10% plasma cells); (4) no anemia, hypercalcemia or renal involvement. The average follow-up period was 112 months (from 6 to 360 months). Fifty-four percent of patients with SBP and 40% of patients with EMP developed MM, however, there was no significant statistical difference between SPB and EMP (P > 0.05). We suggested that solitary plasmacytomas be classified as two types, latent and aggressive. The former was histologically well-differentiated plasmacytoma. The latter was poorly differentiated tumors which easily progress to MM. The treatment of choice is wide excision or thorough curettage, by cryogenic necrosis with liquid nitrogen or cautery of the bony wall with phenol and the cavity filled with bone grafts or cementation. All patients with apparently isolated plasmacytoma should receive local radiotherapy after operation. Adjuvant chemotherapy should be given if the tumour turns out to be poorly differentiated, in order to delay their progression to MM.
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PMID:[Solitary plasmacytomas of bone and extramedullary plasmacytomas]. 873 11

Nitrogen retention of various intensity was found in 61 patients with multiple myeloma. In seven (11%) of them the disturbances of the depurative renal function manifested as acute renal failure (ARF). The syndrome was characterised in etiologic, pathogenetic, clinical, therapeutic and prognostic aspects. ARF in the study developed on the background of a light chain proteinuria in patients with hypercalcemia, dehydration, radiocontrast studies, blood loss, surgical interventions, and severe infections. Following conservative treatment, the renal function normalized in one patient, a gradual transition to chronic renal failure was observed in five patients, and lethal outcome in one patient. The average survival rate after ARF was 8 months (1-13 months).
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PMID:Acute renal failure in patients with multiple myeloma. 900 62

Contrast-media associated nephropathy (CMAN) consists in a sudden impairment of glomerular filtration rate following exposure to radiographic contrast materials. Damage may be limited to an asymptomatic mild increase of blood creatinine, or reach the highest levels of nitrogen retention compatible with acute renal failure. Some preexisting clinical conditions or pathologies may lead to CMAN: not only renal insufficiency, diabetes mellitus, multiple myeloma, congestive heart failure and severe hypertension, but also simple dehydration and a growing series of immunologic diseases are recognized as predisposing condition. The exact mechanism responsible for renal injury is still doubtful but recently animal models have shown substantial ischemic changes that may be added to the traditional presumed pathogenesis of direct tubular toxicity and intra-tubular obstruction. As renal ischemia stimulates both endogenous vasoconstrictor and vasodilator substances, it is now supposed that CMAN acts similarly to non-steroidal anti-inflammatory agents, selectively inhibiting the vasodilatory prostaglandin phase and therefore causing a derangement of the physiologic vasoconstriction/vasodilatation balance of renal circulation. The role of oxygen free radicals to contribute to renal dysfunction is considered. Low osmolality non ionic contrast media when compared to conventional high osmolality ionic contrast media have reduced but not eliminated CMAN. Simple but effective lines of prevention include the previous selection of patients predisposed to CMAN for concomitant pathology, suspension of FANS or any other recognized nephrotoxic substance, the least amount of contrast media compatible with radiologic visualization of the patient's problem, careful hydration of the patient before contrast injection and sustained diuresis afterwards. The usefulness of pre-treatment with Ca-channel blockers or atrial natriuretic factors remains sub judice.
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PMID:[Physiopathology, clinical aspects and prevention of renal insufficiency caused by contrast media]. 917 67

Recombinant human hematopoietic growth factors are widely used in the treatment of multiple myeloma (MM) especially due to the increasing role of autologous blood stem cell transplantation (ABSCT). We report a patient with MM in whom rapid extramedullary progression of disease was observed during stem cell mobilization with G-CSF. In 56-year-old man with relapsing IgG lambda MM myeloablative therapy with ABSCT was planned 2 years after diagnosis. G-CSF is increasing doses was used for mobilization. Ten days after the start of G-CSF therapy 2 extramedullary (subcutaneous) myeloma infiltrates appeared. For the second mobilization high dose cyclophosphamide and VP-16 with subsequent G-CSF was used. During the time of chemotherapy tumour infiltrates disappeared, however, after one week of G-CSF treatment rapid progression of disease with the formation of multiple extramedullary infiltrates occurred and the patient died in June 1996. Small pieces of subcutaneous tumour infiltrates were removed at autopsy and immediately frozen in liquid nitrogen. Using the panel of specific antibodies the expression of cytokine receptors (IL-1, 2, 3, 6, 7, 8, 10, SCF, gp130, G-CSF, GM-CSF, EPO) and Fas, Pgp and 24-34 kD multidrug resistance-associated protein were examined. However, no expression of cytokine receptors on tumor cells was found. On the contrary, high positivity of surface MDR associated proteins was observed.
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PMID:[Progression of multiple myeloma during treatment with recombinant G-CSF and absence of G-CSF and IL-6 cell surface receptors on malignant cells]. 992 31

Bisphosphonates (BPs) used as inhibitors of bone resorption all contain two phosphonate groups attached to a single carbon atom, forming a "P-C-P" structure. The bisphosphonates are therefore stable analogues of naturally occuring pyrophosphate-containing compounds, which now helps to explain their intracellular as well as their extracellular modes of action. Bisphosphonates adsorb to bone mineral and inhibit bone resorption. The mode of action of bisphosphonates was originally ascribed to physico-chemical effects on hydroxyapatite crystals, but it has gradually become clear that cellular effects must also be involved. The marked structure-activity relationships observed among more complex compounds indicate that the pharmacophore required for maximal activity not only depends upon the bisphosphonate moiety but also on key features, e.g., nitrogen substitution in alkyl or heterocyclic side chains. Several bisphosphonates (e.g., etidronate, clodronate, pamidronate, alendronate, tiludronate, risedronate, and ibandronate) are established as effective treatments in clinical disorders such as Paget's disease of bone, myeloma, and bone metastases. Bisphosphonates are also now well established as successful antiresorptive agents for the prevention and treatment of osteoporosis. In particular, etidronate and alendronate are approved as therapies in many countries, and both can increase bone mass and produce a reduction in fracture rates to approximately half of control rates at the spine, hip, and other sites in postmenopausal women. In addition to inhibition of osteoclasts, the ability of bisphosphonates to reduce the activation frequency and birth rates of new bone remodeling units, and possibly to enhance osteon mineralisation, may also contribute to the reduction in fractures. The clinical pharmacology of bisphosphonates is characterized by low intestinal absorption, but highly selective localization and retention in bone. Significant side effects are minimal. Current issues with bisphosphonates include the introduction of new compounds, the choice of therapeutic regimen (e.g., the use of intermittent dosing rather than continuous), intravenous vs. oral therapy, the optimal duration of therapy, the combination with other drugs, and extension of their use to other conditions, including steroid-associated osteoporosis, male osteoporosis, arthritis, and osteopenic disorders in childhood. Bisphosphonates inhibit bone resorption by being selectively taken up and adsorbed to mineral surfaces in bone, where they interfere with the action of osteoclasts. It is likely that bisphosphonates are internalized by osteoclasts and interfere with specific biochemical processes and induce apoptosis. The molecular mechanisms by which these effects are brought about are becoming clearer. Recent studies show that bisphosphonates can be classified into at least two groups with different modes of action. Bisphosphonates that closely resemble pyrophosphate (such as clodronate and etidronate) can be metabolically incorporated into nonhydrolysable analogues of ATP that may inhibit ATP-dependent intracellular enzymes. The more potent, nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, and ibandronate) are not metabolized in this way but can inhibit enzymes of the mevalonate pathway, thereby preventing the biosynthesis of isoprenoid compounds that are essential for the posttranslational modification of small GTPases. The inhibition of protein prenylation and the disruption of the function of these key regulatory proteins explains the loss of osteoclast activity and induction of apoptosis. These different modes of action might account for subtle differences between compounds in terms of their clinical effects. In conclusion, bisphosphonates are now established as an important class of drugs for the treatment of bone diseases, and their mode of action is being unravelled. As a result, their full therapeutic potential is gradual
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PMID:Bisphosphonates: from the laboratory to the clinic and back again. 1042 31

Bisphosphonates are a class of anti-resorptive drugs, which are effective in the treatment of osteoclast-mediated bone disease, including the osteolytic bone disease. which is a major clinical feature of patients with multiple myeloma. Recently, increases in survival following treatment with pamidronate have been observed in some patients with multiple myeloma, raising the possibility that bisphosphonates may also have an anti-tumour effect. We have demonstrated that bisphosphonates can have an anti-tumour effect in human myeloma cell in vitro, and that these anti-tumour effects induced by potent nitrogen-containing bisphosphonates are a result of inhibition of enzymes of the mevalonate pathway. However, we and others have been unable to demonstrate an anti-tumour effect of the potent bisphosphonate ibandronate in vivo, using murine models of multiple myeloma. It is therefore likely that only by studying patients receiving bisphosphonates will we be able to determine whether these compounds have a clinically important anti-tumour effect.
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PMID:Bisphosphonates--mechanisms of action in multiple myeloma. 1114 41

The skeleton is the most common site of metastatic disease in breast cancer and the most common site of first distant relapse. Bone metastases in breast cancer are the source of considerable morbidity, including severe pain, pathological fractures, need for radiotherapy or surgery, and hypercalcemia. Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption, and it is well known that breast cancer cells in bone can stimulate osteoclast formation and activity leading to the release of growth factors and cytokines, which will further stimulate cancer cell growth and their secretion of osteolytic factors. We are thus typically dealing with a vicious cycle, as the bone resorption-induced release of growth factors from the bone matrix will stimulate breast cancer cell growth (probably mainly by IGFs) and the production of the osteolytic factor PTHrP (probably mainly by TGF-beta but also by extracellular calcium). Clodronate, but not the aminobisphosphonates, can be metabolized to an ATP analog that is toxic for osteoclasts. Nitrogen-containing bisphosphonates, such as pamidronate, ibandronate, and zoledronate, interfere with the mevalonate pathway that is crucial to maintain cell membrane integrity. The net result, regardless of the mechanism, is osteoclast apoptosis, notably through the induction of caspase-3. Bisphosphonates are now the standard treatment for cancer hypercalcemia. Repeated bisphosphonate infusions also exert clinically relevant analgesic effects in at least one half of the patients with metastatic bone pain. Most importantly, prolonged administration of bisphosphonates (for at least 1 year) reduces the frequency of morbid skeletal events by 30-40% in breast cancer metastatic to bone and in up to 50% in patients with multiple myeloma. Newer bisphosphonates, such as ibandronate and zoledronate, will simplify the current therapeutic schemes and improve the cost-effectiveness ratio, and they have the potential to improve the therapeutic efficacy, at least in patients with aggressive osteolytic disease or in the adjuvant setting.
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PMID:Bisphosphonates in the treatment of metastatic breast cancer. 1201 36


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