digoxin and Multiple-Myeloma

This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol and ubiquinone in multiple myeloma. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition and free radical metabolism. There was elevation in plasma HMG CoA reductase activity, serum digoxin and dolichol and a reduction in RBC membrane Na+ - K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, nicotine, strychnine and quinolinic acid were elevated while tyrosine, dopamine, noradrenaline and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose and fucose residues of glycoproteins, cholesterol and phospholipids were reduced. The activity of all free radical scavenging enzymes, concentration of glutathione, iron binding capacity and ceruloplasmin decreased significantly while the concentration of lipid peroxidation products and NO increased. Hyperdigoxinemia related altered intracellular Ca++ mediated oncogene activation, dolichol induced altered glycoconjugate metabolism and ubiquinone deficiency related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical findings reported could be the cause or the consequence of multiple myeloma.

Topics: Calcium; Digoxin; Dolichols; Erythrocyte Membrane; Free Radicals; Glycoconjugates; Humans; Hydroxymethylglutaryl CoA Reductases; Middle Aged; Multiple Myeloma; Signal Transduction; Sodium-Potassium-Exchanging ATPase; Terpenes; Tryptophan; Tyrosine; Ubiquinone

This study assessed the changes in the isoprenoid pathway and its metabolites digoxin, dolichol, and ubiquinone in multiple myeloma. The isoprenoid pathway and digoxin status were also studied for comparison in individuals of differing hemispheric dominance to find out the rote of cerebral dominance in the genesis of multiple myeloma and neoplasms. The following parameters were assessed: isoprenoid pathway metabolites, tyrosine and tryptophan catabolites, glycoconjugate metabolism, RBC membrane composition, and free radical metabolism--in multiple myeloma, as well as in individuals of differing hemispheric dominance. There was elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol, and a reduction in RBC membrane Na(+)-K+ ATPase activity, serum ubiquinone, and magnesium levels. Serum tryptophan, serotonin, nicotine, strychnine, and quinolinic acid were elevated, while tyrosine, dopamine, noradrenaline, and morphine were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins, and serum glycolipids were elevated. The RBC membrane glycosaminoglycans, hexose, and fucose residues of glycoproteins, cholesterol, and phospholipids were reduced. The activity of all free-radical scavenging enzymes, concentration of glutathione, iron binding capacity, and ceruloplasmin decreased significantly, while the concentration of lipid peroxidation products and nitric oxide increased. Hyperdigoxinemia-related altered intracellular Ca++/Mg++ ratios mediated oncogene activation, dolichol-induced altered glycoconjugate metabolism, and ubiquinone deficiency-related mitochondrial dysfunction can contribute to the pathogenesis of multiple myeloma. The biochemical patterns obtained in multiple myeloma are similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with multiple myeloma were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Multiple myeloma occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.

Topics: Case-Control Studies; Chromatography, High Pressure Liquid; Digoxin; Dolichols; Dominance, Cerebral; Erythrocyte Membrane; Free Radical Scavengers; Glycoconjugates; Humans; Hydroxymethylglutaryl CoA Reductases; Hypothalamus; Isoproterenol; Lysosomes; Male; Middle Aged; Multiple Myeloma; Neurotransmitter Agents; Random Allocation; Sodium-Potassium-Exchanging ATPase; Ubiquinone

A patient with renal failure due to myeloma kidney and coincident digitalis intoxication due to prescribed daily digoxin administration was treated with digoxin-specific antibody fragments and plasmapheresis. Rapid response to therapy was noted, removal of digoxin-antidigoxin antibody complexes was confirmed, and prevention of delayed rebound toxicity was documented. We suggest that this is the therapy of choice in similar individuals.

Topics: Acute Kidney Injury; Aged; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Multiple Myeloma; Plasmapheresis; Poisoning; Renal Dialysis

Topics: Adult; Aged; Anti-Glomerular Basement Membrane Disease; Digoxin; Female; Glomerulonephritis; Humans; Hypertension, Malignant; Lupus Vulgaris; Lymphoma; Male; Middle Aged; Multiple Myeloma; Nephrotic Syndrome; Plasma Exchange; Plasmapheresis; Purpura, Thrombocytopenic; Vasculitis; Waldenstrom Macroglobulinemia

We compared the advantages of monoclonal antibodies (produced by plasma cell-myeloma cell hybrid lines) and those of conventional antibodies in the radioimmunoassay of digoxin. It was found that antibodies produced by some hybrid cell lines (hybridomas) were highly specific for the digoxin structure; this way the cross-reactions to related structures (e.g. spironolactone) could be avoided. When the hybridoma lines were grown in ascites, the resulting fluid could have as high or higher titre than the serum of a hyperimmunized rabbit. The high titre, the specificity and the permanent growth of the hybridoma lines make them an optimal source of the specific antibody in clinical radioimmunoassays for the measurement of drug or hormone levels.

Topics: Animals; Antibodies; Antibodies, Neoplasm; Antibody Specificity; Cross Reactions; Digoxin; Hybrid Cells; Mice; Mice, Inbred BALB C; Multiple Myeloma; Neoplasms, Experimental; Rabbits; Radioimmunoassay

Topics: Adult; Cardiomegaly; Digoxin; Doxorubicin; Electrocardiography; Female; Heart; Heart Diseases; Heart Failure; Heart Function Tests; Heart Ventricles; Humans; Lymphoma; Male; Middle Aged; Multiple Myeloma; Neoplasms; Prospective Studies

Topics: Atrial Fibrillation; Autopsy; Digoxin; Female; Heart Neoplasms; Humans; Immunoglobulin A; Middle Aged; Multiple Myeloma; Myocardium; Sinoatrial Node