The molecular mechanism of the inherited phosphofructokinase deficiency associated with hemolysis and myopathy.
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Normal human erythrocyte phosphofructokinase (ATP: D-fructose-6, P-1-phosphotransferase, EC 2.7.1.11; PFK) has recently been shown to consist of a heterogeneous mixture of five tetrameric isozymes: M4, M3L, M2L2, ML3, and L4 (M, muscle type; L, liver type). In the light of these findings, we have investigated the molecular basis of the inherited erythrocyte PFK deficiency associated with myopathy and hemolysis (Tarui disease). The propositus, a 31-yr-old male, suffered from muscle weakness and myoglobinuria on exertion. He showed mild erythrocytosis despite laboratory evidence of hemolysis. In his erythrocytes a metabolic crossover point was found at the level of PFK; 2,3-diphosphoglycerate (2,3-DPG) was also significantly reduced. The PFK from the patient's erythrocytes consisted exclusively of the L4 isozyme, and there was a complete absence of the other four. The leukocyte and platelet PFKs from the patient showed normal activities, chromatographic profiles, and precipitation with anti-M4 antibody. These studies provide direct evidence that in Tarui disease the M-type subunits are absent; but the liver- and platelet-type subunits of PFK are unaffected. The paradox of mild erythrocytosis despite hemolysis reflects the decreased production of 2,3-DPG. (+info)
Assay of urinary N-acetyl-beta-glucosaminidase in a centrifugal analyzer.
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We describe a kinetic, fluorometric assay for urinary N-acetyl-beta-glucosaminidase (EC 3.2.1.30) by measurement of the release of 4-methylumbelliferone (7-hydroxy-4-methylcoumarin). The method is simple, involving only a single reagent, and is applicable to the assay of other enzymes that hydrolyze similar fluorescent-labeled substrates. The enzyme distribution in human tissues and fluids is described. The enzyme is present in high concentrations in human kidney, liver, and lung. Its concentration in urine is shown to be a sensitive indicator of early renal damage, which precedes changes in serum creatinine and urinary protein. Assay of the enzyme is quite useful in monitoring renal damage due to myoglobinuria. (+info)
Sonographic findings in myoglobinuric renal failure and their clinical implications.
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Myoglobinuria, which occurs more frequently than previously believed, may lead to acute tubular necrosis and renal failure. It may be recurrent and can result in permanent renal damage. Three cases of myoglobinuria with acute renal failure and abnormal sonograms are reported. (+info)
The forearm ischaemic work test--hazardous to McArdle patients?
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A 57-year-old patient suffering from late-onset McArdle's disease developed myoglobinaemia, massive myoglobinuria and marked serum creatine kinase elevation subsequent to a routinely performed forearm ischaemic work test. Twenty hours after the test, enhancement of 99mTc methylene-diphosphonate activity was demonstrated exclusively in the tested forearm. It is concluded that the forearm ischaemic work test is potentially hazardous to McArdle patients, as it might induce myoglobinuria sufficient to result in acute myoglobinuric renal failure. (+info)
Excretion of myoglobin in urine after cardiac catheterisation.
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Myoglobin levels were assayed in each urine specimen voided during 12 hours before and 48 hours after routine cardiac catheterisation in 146 patients using an indirect haemagglutination method detecting concentrations in excess of 0.015 mg/ml. Myoglobinuria was found in only one patient before but in 39 patients after cardiac catheterisation (27%), either in the first (34 patients) or the second (5 patients) post-catheterisation urine sample. Once detected, myoglobin was present in all subsequent urine specimens for the next 3 to 22 hours (mean 11.8 hours). The mean amount excreted +/- SE was 14.0 +/- 1.6 mg (range 2.6 to 30 mg) excluding the one patient with myoglobinuria before catheterisation. This patient, who had severe aortic stenosis and atherosclerotic heart disease, excreted 130 mg myoglobin. Patients with myoglobinuria required longer screening time to complete the procedures undertaken than those in whom myoglobin was not detected--15.6 +/- 1.4 and 11.1 +/- 0.6 minutes, respectively (mean +/- SE:P less than 0.01). We conclude that myoglobinuria is not uncommon after cardiac catheterisation, and that though the myoglobin detected may be released from skeletal muscle, it could be partly or wholly of cardiac origin and indicate transient, and presumably reversible, myocardial injury. (+info)
Acute lindane poisoning with development of muscle necrosis.
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A 35-year-old man ingested food contaminated with lindane, an insecticide containing almost pure gamma hexachlorocyclohexane. Grand mal seizures and severe acidemia developed rapidly. The seizures recurred for nearly 2 hours, then ceased. In addition, the patient had muscle weakness and pain, headaches, episodic hypertension, myoglobinuria, acute renal failure and anemia. Pancreatitis developed 13 days after the ingestion of lindane. A muscle biopsy on the 15th day of illness demonstrated widespread necrosis and regeneration of muscle fibres. The patient's condition improved and he was discharged 24 days after the onset of his illness. During the year following the poisoning the patient noted difficulty with recent memory, loss of libido and easy fatigability. One year after lindane ingestion the results of physical examination, including those for muscle power and bulk, were normal. (+info)
Exertional heat stroke: the runner's nemesis.
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Heat stroke in distance runners is increasing in frequency. A case is reported of a 41-year-old man who collapsed during a 10-km "fun run" held when the temperature was 31.6 degrees C and the humidity 80%. Acute renal failure (serum creatinine level 1530 mumol/l [17.3 mg/dl]), rhabdomyolysis, disseminated intravascular coagulation and hepatic damage complicated the clinical picture. Repeated peritoneal dialysis and one cycle of hemodialysis because of a very high serum level of uric acid (1.23 mmol/l [20.7 mg/dl]) were required. Although the illness was prolonged, recovery was almost complete, and 4 months after the man's collapse the serum creatinine level had fallen to 133 mumol/l (1.5 mg/dl). (+info)
Combined partial deficiency of muscle carnitine palmitoyltransferase and carnitine with autosomal dominant inheritance.
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The authors studied a 53 year old woman and her 22 year old son with episodes of paroxysmal muscle cramps and dark urines lasting several hours related to high fat diet and strenuous physical exercise beginning on both at age 14 years. The father, paternal uncle, paternal grandfather and another son of the mother also had paroxysmal muscle cramps. The two studied cases showed normal findings for physical evaluation, blood lactate after ischemic exercise, and muscle histology (light and electron microscopy). The serum creatine kinase was elevated in the son and normal in the mother. However, 72 hour fasting significantly raised the serum creatine kinase level in both cases. Plasma concentration of ketone bodies and acid soluble acyl-carnitine increased normally with prolonged fasting. The biochemical evaluation of the muscle tissue revealed intact anaerobic glycolysis and normal glycogen content but combined partial deficiency of muscle carnitine palmitoyltransferase and carnitine in both cases. (+info)