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)

Serum beta2-microglobulin levels were measured by radioimmunoassay in patients with various malignant neoplasms, ascitic patients, and also patients with definite or suspected hepatoma showing variable levels of serum alpha-fetoprotein. Elevated serum beta2-microglobulin levels greater than 2.5 mg/liter were found in various malignant neoplasms, especially in multiple myeloma (66.6%) and hepatoma (60.4%) The ascites/serum ratio of beta2-microglobulin levels in the patients with malignant ascites is significantly higher than in those with non-malignant ascites. However, ascites/serum ratios of total protein, IgG, albumin, creatinine levels were not significantly different between the two groups. Levels of serum beta2-microglobulin were correlated well with those of alpha-fetoprotein in the patients with definite or suspected hepatoma (r=0.72, P less than 0.001). From these results it was concluded that (1) high levels of serum beta2-microglobulin in these patients could be attributed to its hyperproduction by tumor cells or by the cells which had been infiltrated and activated, (2) it is useful to estimate the ascites/serum ratio of beta2-microglobulin levels in differentiating malignant from non-malignant ascites, and (3) it might suggest that a function of beta2-microglobulin is in some way related to that of alpha-fetoprotein, and the alpha-fetoprotein-synthesizing cells secrete a great deal of beta2-microglobulin, although its function remains unclear.
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PMID:Beta2-microglobulin levels of serum and ascites in malignant diseases. 8 Mar 42

Attempts were made to find prognostic factors in myeloma. In 16 deceased patients, urinary light chains, skeletal lesions, and the quantity of the monoclonal protein fraction in the serum were correlated to prognosis, in contrast to the electrophoretic mobility of the monoclonal fraction, the hemoglobin, the serum creatinine value, the serum calcium, or the intestinal calcium absorption. Skeletal calcium uptake was only numerically higher in mild myeloma than in advanced myeloma. Since these findings partially agreed with the staging procedure previously proposed by Salmon, a modification of this procedure was used to stage 50 myeloma patients. Survival was statistically significantly shorter in stage III than in stage I. A differentiated treatement with melphalan-prednisone in stage I, cytoxan infusions in stage II, and vincristine-cytoxan-prednisone in stage III is proposed. A preliminary comparison of nine patients in stage II-III given intensive treatment with 23 given melphalan-prednisone suggests a numerically, but not as yet a statistically significant increase in survival in the intensively treated group, which seems to have an 80% 2-year survival.
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PMID:Staging of myeloma. A preliminary study of staging factors and treatment in different stages. 10 48

The case history of a patient having multiple myeloma with a remarkably high level of Bence Jones proteinuria (more than 20 g/day) is presented. The patient has responded well to therapy, and at no stage has he shown impairment of renal function as determined by creatinine clearance studies. A review of published reports has shown that such marked Bence Jones proteinuria at presentation is rare and is usually accompanied by renal impairment and a short survival. Additional presentation data from selected patients in the MRC First Myelomatosis Trial is presented. This suggests a higher incidence of marked Bence Jones proteinuria, and underlines the lack of correlation between the quantity excreted and the degree of renal impairment. The mechanisms by which Bence Jones protein may cause renal damage are discussed.
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PMID:Multiple myeloma with massive Bence Jones proteinuria and preservation of renal function. 26 96

Twenty-six patients including 11 with metastatic melanoma received cis-dichlorodiammineplatinum(II) at a dose of either 1 mg/kg or 60 mg/m2 given with intensive diuresis over a 6-hour period. This dose was administered twice weekly for the first three to eight courses and then at q3wk intervals. Eighteen patients received the dose schedule of 1 mg/kg and six patients received 60 mg/m2. A complete response was seen in one of four testicular tumors lasting for 6 months; partial responses were seen in three of 11 metastatic melanomas for 1, 1, and 2 months respectively, one of two osteogenic sarcomas for 4 months, one of one multiple myeloma for 2 months, and one of four testicular tumors for 1 month. A transient drop in creatinine clearance to 50%-75% of the baseline level was observed in 21% of the patients. Cytotoxic effects of cis-dichlorodiammineplatinum(II) are probably enhanced by this dose schedule as indicated by the consistent, moderate hematologic toxicity. Renal toxicity is ameliorated.
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PMID:Phase I study of high-dose cis-dichlorodiammineplatinum(II) with forced diuresis. 26 72

Bence Jones proteins (BJP) were isolated from the urine of 12 patients with multiple myeloma and various degrees of renal dysfunction. Proteins were characterized as to type (six type lambda and five type kappa), isoelectric point (pI), and secondary structure by circular dichroism (CD). Clinical renal function was more impaired with type-lambda proteins and with proteins of pI greater than 5.7. CD studies distinguished kappa from lambda proteins in most cases but did not correlate with nephrotoxicity. Protein dimer preparations were tested for nephrotoxicity in aciduric, hydropenic, female, Sprague Dawley rats by following renal function and morphology over 6 hours after injection i.p. of 300 mg of protein. Twelve rats of urine pH less than 5.5 injected with four BJP of pI less than 5.7 showed a mean rise in SUN of 5.3 mg/dl and in creatinine of 0.06 mg/dl, compared with a mean rise of 28.0 mg/dl (SUN) and 0.75 mg/dl (creatinine) in 21 rats injected with seven BJP of pI greater than 5.7 (P less than 0.01). Seven sodium-bicarbonate-fed rats of urine pH greater than 8 injected with a BJP of pI 6.2 showed mean rise in SUN of 1.8 mg/dl and in creatinine of 0.01 mg/dl, compared with 19.3 mg/dl (SUN) and 0.55 mg/dl (creatinine) in 7 aciduric rats injected with the same BJP (P = 0.009). Morphologic and immunohistologic studies showed distal cast formation in 9 rats with acute deterioration in renal function. It is concluded that BJP of pI greater than urine pH are acutely nephrotoxic in the rat by a mechanism that may involve a charge interaction in the distal nephron.
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PMID:Nephrotoxicity of Bence Jones proteins in the rat: importance of protein isoelectric point. 52 81

Patients with asymptomatic or smoldering multiple myeloma should not be treated but should be observed closely for progression. For symptomatic myeloma, chemotherapy is indicated. Melphalan, the agent of choice, should be given with prednisone for 1 week of every 6 weeks, If melphalan brings no response, or response and then relapse, cyclophosphamide (Cytoxan) should be give intravenously every 4 weeks or orally every day. BCNU, CCNU, and doxorubicin (Adriamycin) have also shown activity in myeloma. Hypercalcemia occurs in one-third of patients and should be countered with hydration, corticosteroids, Neutra-Phos, or mithramycin. Long-term hemodialysis has achieved some success. The combination of sodium flouride and calcium carbonate produces new bone formation; it seems a useful adjunct in treatment for myelomatous bone disease. Radiation should be utilized only for severe, localized pain or for solitary lesions. Survival with multiple myeloma varies, mean durations being 2 to 3 years. Multivariate analysis indicates that serum creatinine and calcium levels are the most significant indicators regarding 2-year survival. We have found monoclonal proteinuria not significantly more frequent with renal insufficiency than with normal renal function, renal insufficiency not significantly more frequent with lambda than with kappa chains, and survival not significantly greater with IgG myeloma than with IgA.
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PMID:Management and prognosis of multiple myeloma. 79 81

Protein studies measuring selected serum and urinary biopolymers, representing activities of different organ systems, e.g., IgG, IgA, and C'3 complement (reticuloendothelial system), and albumin, transferrin, ceruloplasmin, and alpha-2 macroglobulin (liver) are compared and discussed. Mean normal excretions were 2.91 mg. per 24 hr. for IgG, 2.00 mg. per 24 hr. for IgA, and 20.39 mg. per 24 hr. for albumin. Renal function was estimated using creatinine clearance. The data suggest that concentration variations in certain of the proteins of the plasma pool are related to altered renal function. Such differences strayed below the normal but little, yet significant quantities of these proteins were found in urine. The identification and quantitation of abnormal urinary protein components in urine of patients who have myelomatosis and macrogammaglobulinemia may eventually be useful in medical management.
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PMID:Multiple myeloma and macrogammaglobulinemia. I. Urinary protein excretions and serum interrelationships. 80 16

Serum RNase levels were measured in 34 patients with multiple myeloma and compared with 51 normal controls and 28 non-myeloma patients on chronic hemodialysis. Nineteen of the myeloma patinets with creatinine clearance (CCr) greater than 50 ml/minute had mean serum RNase levels that were statistically indistinguishable from those of the normal controls. The 15 myeloma patinets with CCr less than 50 ml/minute had mean RNase levels much higher than normal controls or myeloma patients with normal renal function. Patients without myeloma but on hemodialysis for chronic renal failure of varied etiologies had markedly elevated serum RNase levels. A strong correlation between RNase levels and renal insufficiency, as measured by CCr, has thus been demonstrated. In addition, case histories of 5 representative myeloma patients were analyzed in greater detail; they illustrated the rise and fall of RNase levels as a function of the status of their renal insufficiency, regardless of the extent of the underlying myeloma. We concluded that the serum RNase level was an indicator of renal function, and was not a biomarker either for the presence or extent of the plasma cell tumor.
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PMID:Influence of renal insufficiency on levels of serum ribonuclease in patients with multiple myeloma. 84 91

An improved knowledge of the initial prognostic factors of multiple myeloma and regular monitoring of the disease should result in the choice of the most effective treatment. The conventional prognostic factors have been divided into three stages by Durie and Salmon. These stages are based on the proportion and type of the monoclonal component, on haemoglobin, calcium and creatinine blood levels and on the extent of bone lesions. However, this widely used classification has certain disadvantages: the size of the tumoral mass is evaluated mainly from the proportion of monoclonal gammopathy, the bone lesions are difficult to determine and the kinetics of cell proliferation are not taken into account. Parameters with high prognostic value have recently been demonstrated; they include beta 2-microglobulin, LDH, interleukin-6, C-reactive protein, serum albumin and kinetic of cell proliferation. When associated, these data allow to establish prognostic staying that are at least as relevant as those of the Durie-Salmon's classification. Monitoring of patients with multiple myeloma by means of a time-related curve of either the tumoral mass or the amount of monoclonal gammopathy leads to the best possible treatment.
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PMID:[Prognostic factors and monitoring of myeloma]. 128 67

The activities of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl-transpeptidase (gamma-GTP) and NAG isoenzyme were measured in the urine of 20 patients with multiple myeloma (IgG/IgA type/Bense Jones type; 15/1/4 cases) and 25 healthy controls to evaluate these activities as indicators of renal disturbance in multiple myeloma. NAG isoenzyme fractions in urine were measured by agarose electrophoresis-m-cresol sulfonphthaleinyl-NAG reaction. Mean urinary NAG activity in the patients with myeloma was significantly higher than that in the controls (20.1 +/- 3.3 vs 4.3 +/- 0.3U/g. cr; p < 0.001). Urinary NAG activity in these patients correlated positively with the dose (mg/g. cr) of urinary protein (r = 0.755; p < 0.01), most of which were considered to be light chain protein, but not with creatinine clearance. Each urinary NAG isoenzyme fraction (NAG-1, -2, -3) was higher in the patients than that in the controls, and especially NAG-2 fraction (A form) showed a highly positive correlation with the dose of urinary protein. Urinary gamma-GTP activity in the patients did not differ from that in the controls, but urinary NAG/gamma-GTP ratio was higher in the patients, and reversely correlated with creatinine clearance (r = -0.721; p < 0.01). It is suggested that the elevation of urinary NAG activity results from the damage of lysosome in proximal tubular cells by urinary light chain protein and its degradation products. Therefore, urinary NAG activity may be a good index for proximal tubular disturbance, and NAG/gamma-GTP ratio may be an index for the extensive damage of nephrons in addition to the damage of tubular cells in multiple myeloma.
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PMID:[Urinary N-acetyl-beta-D-glucosaminidase and gamma-glutamyl-transpeptidase activities for evaluation of renal disturbance in patients with multiple myeloma]. 136 43


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