ABSTRACT
A 33-year-old woman with congenital heart disease and atrial and ventricular arrhythmias, managed over the long term with an implantable cardioverter defibrillator, epicardial pacing system, and amiodarone, experienced an increase in palpitations and a shock from her defibrillator. Evaluation revealed decreases in amiodarone and desethylamiodarone serum concentrations from previous levels. Rifampin had been added to her therapy 5 weeks earlier. Increases in amiodarone and desethylamiodarone concentrations were observed after an increase in the amiodarone dosage and discontinuation of rifampin. The time course suggested that the addition of rifampin led to reductions in serum concentrations of both the drug and metabolite.
Subject(s)
Amiodarone/blood , Antibiotics, Antitubercular/adverse effects , Arrhythmias, Cardiac/blood , Heart Defects, Congenital/blood , Rifampin/adverse effects , Adult , Antibiotics, Antitubercular/therapeutic use , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/therapy , Defibrillators, Implantable , Female , Heart Defects, Congenital/complications , Heart Defects, Congenital/therapy , Humans , Rifampin/therapeutic useSubject(s)
Cells, Cultured , Fibroblasts , Leukodystrophy, Metachromatic/drug therapy , Sulfatases/therapeutic use , Culture Media , Fibroblasts/enzymology , Fibroblasts/immunology , Fibroblasts/metabolism , Fibroblasts/pathology , Hydrolysis , Leukodystrophy, Metachromatic/classification , Leukodystrophy, Metachromatic/enzymology , Leukodystrophy, Metachromatic/immunology , Leukodystrophy, Metachromatic/pathology , Sulfatases/isolation & purification , Sulfatases/metabolism , Sulfoglycosphingolipids/metabolism , Sulfur RadioisotopesSubject(s)
Amino Acid Metabolism, Inborn Errors/genetics , Antipsychotic Agents/adverse effects , Intellectual Disability/complications , Renal Aminoacidurias/genetics , Adolescent , Arginine/blood , Arginine/urine , Chlorpromazine/adverse effects , Cystinuria , Female , Fluphenazine/adverse effects , Humans , Intestinal Absorption , Kidney Tubules/physiopathology , Lysine/blood , Lysine/urine , Movement Disorders/chemically induced , Ornithine/blood , Ornithine/urine , Pedigree , Renal Aminoacidurias/physiopathology , Thioridazine/adverse effects , Trihexyphenidyl/adverse effectsSubject(s)
Amniotic Fluid/enzymology , Glucosidases/metabolism , Carbon Isotopes , Cardiomegaly/diagnosis , Clinical Enzyme Tests , Disaccharides/pharmacology , Drug Stability , Embryonic and Fetal Development , Evaluation Studies as Topic , Female , Fibroblasts/enzymology , Gestational Age , Glycogen Storage Disease/diagnosis , Glycoside Hydrolases/metabolism , Heart Defects, Congenital/diagnosis , Heart Diseases/diagnosis , Hot Temperature , Humans , Hydrogen-Ion Concentration , Lysosomes/enzymology , Maltose , Nitrobenzenes , Potassium Chloride/pharmacology , PregnancySubject(s)
Diffuse Cerebral Sclerosis of Schilder/genetics , Heterozygote , Leukocytes/enzymology , Sulfatases/blood , Clinical Enzyme Tests , Culture Techniques , Diffuse Cerebral Sclerosis of Schilder/diagnosis , Diffuse Cerebral Sclerosis of Schilder/enzymology , Female , Fibroblasts/enzymology , Genes, Recessive , Humans , MaleSubject(s)
Fibroblasts/enzymology , Skin/enzymology , Sulfatases/analysis , Animals , Bile Acids and Salts , Brain/metabolism , Catechols , Cells, Cultured , Cerebrosides , Chlorides , Enzyme Activation , Humans , Hydrogen-Ion Concentration , Kinetics , Manganese , Nitrophenols , Rats , Sulfates/metabolism , Sulfoglycosphingolipids/biosynthesis , Sulfur IsotopesSubject(s)
Diffuse Cerebral Sclerosis of Schilder/enzymology , Fibroblasts/enzymology , Sulfatases , Adolescent , Adult , Age Factors , Biological Transport , Cells, Cultured/enzymology , Cells, Cultured/metabolism , Cerebrosides/metabolism , Child , Child, Preschool , Humans , Hydrolysis , Infant , Kinetics , Skin , Sulfoglycosphingolipids/metabolism , Sulfur IsotopesABSTRACT
Cultured fibroblasts derived from patients with late infantile metachromatic leukodystrophy incorporated arylsulfatase A from the growth medium. Upon exposure to cerebroside sulfate, they exhibited patterns of uptake and hydrolysis indistinguishable from cells derived from control subjects. Furthermore, inclusion granules formed in the metachromatic leukodystrophy fibroblasts upon exposure to sulfatides were cleared by subsequent supplementation of the growth medium with arylsulfatase A.
Subject(s)
Cerebrosides/metabolism , Diffuse Cerebral Sclerosis of Schilder/metabolism , Fibroblasts/metabolism , Sulfates/metabolism , Culture Media , Culture Techniques , Hydrolysis , Sulfatases/metabolism , Sulfur IsotopesSubject(s)
Galactosidases/isolation & purification , Animals , Cattle , Cells, Cultured , Chloromercuribenzoates , Coumarins , Electrophoresis/instrumentation , Fibroblasts/enzymology , Fluorescence , Galactosidases/antagonists & inhibitors , Humans , Hydrogen-Ion Concentration , Kidney/enzymology , Lactones , Lactose , Liver/cytology , Liver/enzymology , Lysosomes/enzymology , Methods , Mucopolysaccharidoses/enzymology , Osmolar Concentration , Phenols , Retinitis Pigmentosa/enzymology , Time FactorsSubject(s)
Acid Phosphatase/metabolism , Glucosidases/metabolism , Hydrolases/metabolism , Lyases/metabolism , Myxomycetes/enzymology , Oxidoreductases/metabolism , Cycloheximide/pharmacology , Dactinomycin/pharmacology , Enzyme Induction , Glucosephosphate Dehydrogenase/metabolism , Glutamate Dehydrogenase/metabolism , Hydrogen-Ion Concentration , Isocitrate Dehydrogenase/metabolism , Mitosis , Myxomycetes/drug effects , Myxomycetes/growth & developmentSubject(s)
Fibroblasts/drug effects , Glycosaminoglycans/biosynthesis , Adult , Culture Techniques , Dextrans/pharmacology , Fibroblasts/cytology , Fibroblasts/metabolism , Humans , Infant , Infant, Newborn , Polyvinyls/pharmacology , Staining and Labeling , Sulfuric Acids/pharmacology , Time FactorsSubject(s)
Carbohydrate Metabolism, Inborn Errors/enzymology , Fibroblasts/enzymology , Galactosidases/analysis , Glucuronidase/analysis , Glycosaminoglycans/metabolism , Glycoside Hydrolases/analysis , Intellectual Disability/enzymology , Mucopolysaccharidoses/enzymology , Retinitis Pigmentosa/enzymology , Acetates , Electrophoresis , Female , Fluorometry , Glucosamine , Glucosephosphate Dehydrogenase/analysis , Humans , Male , Mucopolysaccharidoses/genetics , SpectrophotometryABSTRACT
Fibroblasts cultured from the skin of a patient with metachromatic leukodystrophy have been found to manifest the biochemical defect of this inborn error of metabolism, a deficiency of arylsulfatase A. Diseased cells had less than five per cent of normal arylsulfatase-A activity, while activities of other lysosomal enzymes-including arylsulfatase B, beta-galactosidase, beta-glucuronidase, and beta-N-acetylglucosaminidase-were comparable to those in control cells. The presence of dissociable inhibitors in extracts of the diseased cells was excluded by combination experiments. The deficiency of the enzyme in leukocytes was also confirmed and is comparable to that found in cultured fibroblasts. The finding that readily cultured fibroblasts from easily obtained skin biopsy specimens exhibit the enzymatic defect should prove valuable in the biochemical study of this disease.