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)

The most common cause of limited response to recombinant human erythropoietin (r-HuEPO) is unrecognized, mild-to-moderate iron deficiency, either at the start of treatment or secondary to enhanced iron utilization by newly formed erythrocytes. Iron stores in patients with chronic renal failure (CRF) are often depleted through gastrointestinal bleeding, blood loss during haemodialysis, and blood sampling. Mobilization of iron stores may be inadequate, especially during rapid haemoglobin regeneration. Aluminium overload may also interfere with gastrointestinal and cellular iron uptake. Overt or unrecognized infection or inflammation is another common cause of hyporesponsiveness, and is a consequence of increased blood concentrations of cytokines such as tumour necrosis factor (TNF), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma), which suppress erythrocyte stem-cell proliferation. Less common causes include severe secondary hyperparathyroidism and myeloma (during chemotherapy). Response to r-HuEPO can be best predicted by baseline fibrinogen (a marker of subclinical inflammation); baseline transferrin receptor (sTfR) concentrations (a marker of functional iron deficiency); and sTfR increment after 2 weeks (a marker of early change in erythropoietic activity).
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PMID:R-HuEPO hyporesponsiveness--who and why? 764 9

Anemia and bleeding are commonly observed in patients with multiple myeloma (MM). Anemia in MM is multifactorial in origin. Three common causes are marrow replacement by the malignant cells, thereby reducing the available number of BFU-E, chronic renal failure and shortening of the half life of erythrocytes. Some patients with anemia but without renal failure show a good response to erythropoietin (Epo) with full correction of anemia. This indicates that human Epo is a promising therapeutic tool or treating myeloma-associated anemia. The incidence of severe bleeding complications is low, despite the diversity of abnormal hemostatic tests in patients with MM. These patients frequently show abnormal coagulation tests, including thrombin time, fibrin degeneration products, platelet aggregation tests and bleeding time. The most effective therapeutic approach to bleeding is to treat the underlying malignancy. Supplemental to this, plasma exchange is useful.
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PMID:[Anemia and hemostatic abnormalities associated with multiple myeloma]. 769 6

Administration of iodinated contrast media (CM) for radiographic purposes is a preoccupying cause of acute renal failure. This review of the literature deals with what is known about physiopathology, clinical course, risk factors and prevention. Factors involved in the pathophysiology of CM-induced acute renal failure are vasoconstriction, direct tubular cell injury and tubular obstruction by casts. In the case of pre-existing renal hypoperfusion, CM may disturb the complex interaction between factors which modulate renal haemodynamics by increasing vasoconstrictor factors, notably endothelin peptides. The renal medulla, a zone characterized by a high metabolic activity and a low oxygen tension, may be a specific target for CM-induced effects. CM-induced nephropathy (CMN) is essentially observed in patients with one or more associated risk factors (chronic renal failure, dehydration, diabetes mellitus with impaired renal function, multiple myeloma, large CM volume, intra-arterial rather than intravenous route, etc). There is much debate as to whether newer low osmolar CM (LOCM) are better tolerated than conventional high osmolar CM (HOCM). Most of the animal studies clearly demonstrate the advantages of LOCM over HOCM. Clinical literature is far more confusing, although some recent studies and one meta-analysis demonstrate that LOCM are better tolerated in patients with impaired renal function. The low number of comparative clinical trials carried out in high risk patients, wide variability in CMN definitions, limited number of patients enrolled and inadequacy of various selected endpoints may explain difficulties experienced in demonstrating this advantage. Furthermore, while hydration is correctly maintained during clinical trials, this is not always true in clinical practice. Such a discrepancy could lead to underestimation of the potential advantage of LOCM over HOCM. Effective prevention should associate the correct hydration of patients, identification and, when possible, optimal correction of risk factors, avoidance of repeated CM injections within a short period of time and temporary disruption of treatment with other nephrotoxic drugs (non steroidal antiinflammatory drugs, aminoglycosides, etc).
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PMID:Iodinated contrast media-induced nephropathy: pathophysiology, clinical aspects and prevention. 792 15

Nowadays, maintenance dialysis can be proposed to patients suffering from myeloma with end-stage chronic renal failure. We report here data from eight patients dialysed either by hemo- (6) or peritoneal dialysis (2), together with chemotherapy in half of them. Six patients died; the longest survival has been about 6 years. The main cause of morbidity was sepsis, especially in peritoneal dialysis patients; therefore we now favour hemodialysis in patients exposed to aggressive chemotherapy. We think dialysis justified in all cases, including those with high tumor mass, in order to expect the effect of chemotherapy; then, provided good response to drugs, further survival can be consistently improved. Once on maintenance dialysis, main drawbacks for these patients are cardiovascular complications (AL amyloidosis) and above all anemia; the latter however can be markedly improved, thanks to erythropoietin therapy which provides these patients with much better quality of life.
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PMID:[End-stage chronic renal failure in myeloma: results of dialysis]. 819 Oct 93

We report a case of a 40-year-old woman with benign monoclonal gammopathy who developed focal segmental glomerulosclerosis associated with widespread deposition of large crystalline inclusions in the glomerular podocytes. Electron microscopy showed that the crystalline structures were electron dense and needle shaped or polygonal. At a higher magnification, they were seen to be surrounded by unit membranes and to feature a longitudinal filamentous substructure. These inclusions showed positive immunohistochemical staining for kappa light chain. Clinically, the patient had shown nephrotic syndrome on the first medical examination, and later revealed chronic renal failure and monoclonal gammopathy of the immunoglobulin G kappa type, but no evidence of multiple myeloma or other lymphoproliferative diseases. This patient seems to have had a rare form of glomerular involvement associated with benign monoclonal gammopathy.
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PMID:Crystalline inclusions in the glomerular podocytes in a patient with benign monoclonal gammopathy and focal segmental glomerulosclerosis. 820 69

A radioimmunoassay for circulating levels of the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP) was developed and can be available as a kit on a commercial base. Using the kits, we evaluated basically and clinically the assay. The assayed values were reproducible and the assay can detect as low as 0.5 ng/ml of 1CTP. In healthy volunteers, circulating level was high under age 24 and over age 46. In patients with bone metastasis, serum levels elevated even in its early stage and correlated well with clinical status. In other bone diseases, such as primary hyperparathyroidism, hyperthyroidism, post-gastrectomy, hypercalcemia of malignancy and myeloma, serum levels elevated according to their clinical conditions. In patients with chronic renal failure, serum levels were high, suggesting decrease of renal clearance of 1CTP. The circulating 1CTP levels seemed to reflect well clinical bone destructive status. A high correlation between serum 1CTP level and urinary pyridinoline (r = 0.884) was shown, whereas essentially no correlation was observed between bone formation markers such as osteocalcin and alkaline phosphatase. Thus, the measurement of circulating 1CTP seems to be a simple and sensitive method to monitor bone destruction.
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PMID:[Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP)--some basic aspects of the RIA kit and clinical evaluation in various bone diseases]. 827 4

The 9697 electrophoretograms performed over an 8 year period were reviewed to identify the frequency and clinical associations of the finding of a prominent transthyretin band in serum or urine, the concentration of which was equal to or greater than a 64 mg/dL protein calibrator. All samples were electrophoresed at a constant 90 V using agarose gels with a barbital buffer pH 8.6 and Ponceau S staining. Reference calibrators were used as standards to identify increased transthyretin bands and the patients' clinical records were subsequently reviewed. High values were found in 46 patients' sera and a further nine patients' urines representing 0.57% of the total workload. Renal impairment was present in 58% of cases including those with chronic renal failure, the nephrotic syndrome and paraproteinaemia. The high levels were not persistent in three myeloma cases where there was a recovery in renal function following chemotherapy. In some nephrotics, a high urine transthyretin may be secondary to a general hepatic albumin and transport protein synthesis response to severe proteinuria. Why the serum transthyretin was elevated in many other cases remains unclear.
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PMID:Clinical associations of an increased transthyretin band in routine serum and urine protein electrophoresis. 830 23

Glomerulotubular disconnections at the immediate postglomerular segment of the proximal tubules, accounting for an impaired renal function, were demonstrated recently in several chronic nonglomerular renal disorders. To analyze the glomerulotubular junctions in Bence Jones cast nephropathy, paraffin blocks from the kidneys of nine deceased patients with myeloma and chronic renal failure on whom autopsies were performed were studied in serial sections. Kidneys from seven deceased patients without renal disease on whom autopsies also were done served as controls. For stereological estimations, the percentages of patent and sclerosed glomerular profiles, the relative volume fractions, and the absolute volumes of the interstitium, tubules, and glomeruli were determined. In Bence Jones cast nephropathy, 96% of the glomerular profiles were patent, and the reconstruction of randomly chosen glomerulotubular junctions revealed that 84% of the patent glomeruli had normal tubular connections. There was an increased relative interstitial volume (fibrous tissue) and a decreased relative tubular volume. The absolute values indicated severe interstitial fibrosis, but not tubular atrophy. The results show that in contrast with other chronic nonglomerular nephropathies, chronic renal failure in Bence Jones cast nephropathy does not result from nephron disconnection at the immediate postglomerular segment of the proximal tubules. The main factor responsible for the decrease in renal function appears to be the progressive severe fibrosis of the interstitium.
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PMID:Development of chronic renal failure in patients with multiple myeloma. 834 49

Renal diseases characterized by Congo red-negative extracellular fibrillary deposits, either organized arrays of larger, microtubular fibrils (immunotactoid glomerulopathy [IT]) or smaller, randomly organized fibrils (fibrillary glomerulonephritis), have been recognized recently. The clinical significance, if any, of the distinction of these patterns has not been determined. On review of all renal biopsy specimens evaluated in a private referral renal pathology laboratory over the last 11 years, 26 cases with fibrillary glomerulonephritis pattern were identified and compared with our six most recent cases with the IT pattern. The fibrillary glomerulonephritis patients, 17 women and nine men, had an average age of 50 +/- 2 years and contributed 1% of the renal biopsy specimens examined. All patients had marked proteinuria and 16 had microscopic hematuria. Follow-up at 23 +/- 5 months in 25 of these patients revealed end-stage renal disease in 11 patients (44%) and one death due to renal failure. End-stage renal disease developed an average of 10 +/- 5 months after biopsy. One patient developed multiple myeloma. Twenty-four renal biopsy specimens showed proliferation, with crescents in seven. Immunofluorescence showed moderate to intense staining for immunoglobulin G and weaker staining for C3, in a predominantly mesangial pattern, with weaker glomerular basement membrane (GBM) staining, corresponding to electron microscopic deposit localization. In four cases, linear GBM staining by immunofluorescence corresponded to extensive subendothelial or transmembranous deposits. The average fibril diameter was 14.0 +/- 0.5 nm (range, 10.4 to 18.4 nm). Immunotactoid glomerulopathy patients (three women and three men) were significantly older, 62 +/- 2 years (P < 0.025). All had marked proteinuria, with microscopic hematuria in two patients. Associated hematopoietic diseases were present in four patients, with monoclonal proteins and/or abnormal plasma cell proliferation in three. One patient died of nonrenal causes. The remaining five patients have stable renal function at 20 +/- 5 months. Biopsy specimens showed proliferative (n = 3) or membranous-like (n = 3) patterns. Immunofluorescence showed immunoglobulin G and weaker C3 staining in a granular GBM pattern, with lesser mesangial staining. The microtubular fibril diameter was on average 43.2 +/- 10.3 nm (range, 16.8 to 90.0 nm). Thus, fibrillary glomerulonephritis and IT can be separated based on ultrastructurally distinct features. Patients with fibrillary glomerulonephritis are less likely than those with IT to have associated hematopoietic disease and also have poorer renal survival. We propose that classification based on these morphologic differences appears to have clinical significance.
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PMID:Morphologic and clinical features of fibrillary glomerulonephritis versus immunotactoid glomerulopathy. 837 43

Longer and better survival of End-Stage Renal Disease (ESRD) patients undergoing renal replacement therapy (RRT) is now associated with a higher prevalence of new elderly patients receiving renal replacement therapy (dialysis). In order to help clarify the association of cancer risk with RRT, the incidence of cancer in a population-based cohort of uraemic patients in the Region of Lombardy, northern Italy, was undertaken using data from the Lombardy Regional Dialysis and Renal Transplant Registry. A total of 479 cases of cancer of all sites was recorded in this population. There were statistically significantly elevated risks of primary liver cancer, kidney cancer, thyroid cancer, lymphoma and multiple myeloma. When the data were examined according to primary renal diseases, there did not appear to be any particular association between excess cancer risk and the underlying pathology. While some caution must be expressed in interpreting these data, due to the relatively small numbers of cases expected in many of the disease entities, the results indicate an excess of renal-cell and liver carcinomas and lymphomas in patients receiving RRT and highlight the necessity of careful follow-up and awareness of these associations, together with the need for early detection of such tumours.
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PMID:Cancer among patients on renal replacement therapy: a population-based survey in Lombardy, Italy. 864 17


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