Serum myoglobin concentrations

A 73-year-old man took an unknown number of theophylline modified-release tablets and furosemide 40 mg tablets. He developed a tachydysrhythmia, vomiting, and restlessness. His maximum theophylline concentration was 67 pg/ml and he had hypokalemia (2.8 mmol/1) and hyponatremia (123 mmol/1). The maximum creatine kinase activity was (32 mol/1 [sic]) and the serum myoglobin concentration was 3789 pg/l. He was treated with oral activated charcoal, continuous venovenous hemodialysis, intravenous potassium and sodium chloride, forced diuresis, and continuous intravenous meto-prolol, and survived without sequelae. 

A 71-year-old woman took sertraline 50 mg/day for depression and 2 months later was found to have markedly increased creatine kinase, lactate dehydrogenase, and aspartate aminotransferase activities and serum myoglobin concentration. These abnormalities resolved within 1 week of sertraline withdrawal, but recurred dramatically 2 weeks after re-introduc-tion of sertraline. Once again, everything resolved after withdrawal of sertraline. She was successfully treated with escitalopram without recurrence of the biochemical disturbances. 

All patients with major patterns are monitored for rhabdomyolysis and renal failure. An early sign of rhabdomyolysis is an elevated serum uric acid, associated with an increase in serum CK. Within 8 to 12 hours, the serum tests are repeated. If the uric acid falls and the CK rises, rhabdomyolysis is likely. Renal function tests may also be increased at this time. When the diagnosis of rhabdomyolysis is made, the patient is treated with 40 mg furose-mide IV once, and IV fluids. Urine myoglobin concentrations are obtained. If the patient develops renal failure, hemodialysis or peritoneal dialysis may be necessary. In all cases, multiple drug intoxication, trauma, and rhabdomyolysis are ruled out or treated. All patients are kept under observation until they are asymptomatic. 

Myoglobinuria (79) and raised serum creatine kinase activity (44) have been reported after suxamethonium and appear to be evidence of muscle damage, probably resulting from fasciculation. Repeated bolus doses of suxamethonium result in higher plasma myoglobin concentrations (80) and creatine kinase activities (44). Myoglobinemia seems to be much more common in children than in adults (SEDA-10,107) (SEDA-11,121) (81) and is more marked when halothane is used (82). On occasion, myoglobinuria results in renal insufficiency (83-88). 

Vaananen HK, Syrjala H, Rahkila P, Vuori J, Melamies LM, MyUyla V, et al. Serum carbonic anhydrase III and myoglobin concentrations in acute myocardial infarction. Chn Chem 1990 36 635-8. 

In the acute setting of cocaine-induced chest pain, assessment includes the possible diagnosis of acute myocardial infarction. However, cocaine may independently affect cardiac biomarkers [22 ]. Recent cocaine use may alter the specificity of measurement of serum creatine kinase and its MB Iraction. Among cocaine users, increased serum creatine kinase activities and increased mean myoglobin concentrations are common. Increased skeletal muscle activity and rhab-domyolysis are often present, possibly because of cocaine-induced hyperthermia. Troponin I concentrations are more reliable cardiac biomarkers for detecting cocaine-induced myocardial infarction and are associated with a poor prognosis. 

An 85-year-old woman with a schizoaffective disorder was given valproate 600 mg/day and after 4 days complained of muscle pain and weakness. Other medications were quetiapine 200 mg/day, nifedipine 10 mg/day, torsemide 10 mg/day, levothyroxine 75 micrograms/day, and acetylsalicylic acid 100 mg/day. There was a fivefold increase in myoglobin concentration (292 ig/l), a sixfold increase in creatine kinase activity (14 pmol/l), and slightly increased liver enzyme activities. The serum... 

The first four materials (IRMM/IFCC-452, 453, 454, 455) are expected to be released during 2000. Projects on the certification of reference materials for cardiac marker (myoglobin) and total protein concentration in serum are under discussion. Even so the number of available CRMs for clinical chemistry and occupational toxicology is still limited. This has to do with the complexity of physiological compounds (e.g. proteins), the instabihty (e.g. enzymes), or the volatility (e.g. solvents). 

Eu3+, Tb3+, Sm3+, Dy3+ complexes have different emission wavelengths with sharp peak profiles, which are suitable for multi-component immunoassay. Several Eu-Sm two-color time-resolved immunoassays have been reported. Since the sensitivity of Sm3+ chelates is not high compared to Eu3+ and Tb3+, Eu-Sm two-color assays are used for the simultaneous determination of a low concentration component (Eu) and a relatively high concentration component (Sm) in serum the assayed combinations are lutropin and follitropin, myoglobin and carbonic dehydratase, AFP and free (3-subunit of human chorionic gonadotrophin (Hemmila et al., 1987). Use of Eu-Tb is reported by Eriksson et al. (2000) for the simultaneous determination of human serum free and total PSA. 

FIGURE 16 Effect of PEG concentration difference in the two phases on partition coefficient K in PEG 6000-dextran 70-water system containing 0.15 mol /kg NaCI in 0.01 mol /kg sodium phosphate buffer at pH 7.4 (I) myoglobin, (2) cytochrome c, (3) human serum albumin. (Reprinted from Zaslavsky8 by courtesy of Marcel Dekker, Inc.)... 

The influence of various mobile-phase additives on separation and detection of proteins after RPLC-MS was systematically studied by Garcia et al. [44]. First, the response of myoglobin, cytochrome c, and bovine serum albumin (BSA) in ESI-MS was evaluated by column-bypass injections. The best response was achieved using 0.2% formic acid, followed by 0.3% acetic acid, 10 mmol/1 ammonium formate (pH 3), and 50 mmol/1 ammonium bicarbonate (pH 9). Poor responses were achieved with TFA, and 10 mmoPl ammonium formate or acetate (pH 6). Low additive concentrations were favourable, except for ammonium bicarbonate. Separation of these proteins in RPLC could only be achieved using TFA, formic and acetic acid as additive. Formic acid showed poor recovery of the proteins from the column, while TFA resulted in signal suppression. Therefore, the use of acetic acid was preferred. 

Nephelometric methods in general are more sensitive than turbidimetric assays and have an average lower limit of detection of 0.1 to 10 mg/L for a serum protein. Lower detection limits are obtained in fluids, such as cerebrospinal fluid and urine, because of their lower lipid and protein concentrations, which results in a better signal-to-noise ratio. In addition, for low molecular weight proteins (e.g., myoglobin, MW 17,800), assay detection Emits can be lowered using a latex-enhanced procedure based on antibody-coated latex beads. ... 

Elevations in cTnl and cTnT are highly specific for myocardial injury. However, in individuals without myocardial disease, their levels are very low to undetectable. This is in contrast to the low but measurable concentrations of CK-2 and myoglobin detected in serum from skeletal muscle turnover in patients with noncardiac-related diseases and in normal individuals. Therefore release of cTnl or cTnT from myocardium into the blood following AMI and after the washout that accompanies successful reperfusion generates an excellent signal compared with no detectable baseline levels before myocardial damage. The initial rapid release of cardiac troponin subunits I and T following successful reperfusion is most hkely derived from the soluble cytosolic myocardial fraction (6% cTnT 3% cTnl). 

In practice, the laboratory becomes involved if a serum test is available as an early marker to assess successful reperfusion after AMI. With early, frequent serum sampling, it may be possible to use the rate of increase in a cardiac bio-marker (cTnl, cTnT, myoglobin, and CK-2) concentration to... 

Figure 44-30 Time course (mean and standard error) of serum cardiac troponin (cTnl), cardiac troponin T (cTnT), creatine kinase-2 (CK-MB), and myoglobin (MYO) concentrations after initiation of thrombolytic therapy in patients withTIMi Grade 3 reperfusion flow. (From Apple FS, Sharkey SVV Henry TD. Early serum cardiac troponin I and T concentrations following successful thrombolysis for acute myocardial infarction, Clin Chem I995 4I 1197-8.)...

Development of electrophoretic protein separation techniques have been paralleled by improvements in protein detection methods. Protein detection in early electrophoretic applications, utilizing electrophoretic separations of solutions or colloidal suspensions from about 1816 to 1937, was limited to direct visualization of proteins coated onto microspheres, or studies of naturally colored proteins such as hemoglobin, myoglobin, or ferritin <1-4). An increase in sensitivity and the ability to detect non-colored proteins was achieved by the use of the specific absorption, by proteins, of ultraviolet light. This detection technique permitted Tiselius,in 1937, to demonstrate the quantitative electrophoretic separation of ovalbumin, serum globulin fractions and Bence Jones proteins (S). Tiselius also employed the shadows, or schlieren, created by the boundaries, due to the different concentrations of proteins in the electrophoretic system to detect protein position and concentration ( ). These detection methods served as the main methods for protein detection in the liquid electrophoresis systems. However,... 

Figure 7-5 The ionic strength dependence of the monomer/dimer equilibrium of P. denitrificans cytochrome C550- Cytochrome csso (2.3 nmol) dissolved in 10 mM Hepes, pH 8.0, containing the appropriate NaCl concentration, were passed down a Superdex 75 column equilibrated in the same buffer. The elution volume was compared with a set of standards (serum albumin, ovalbumin, carbonic anhy-drase, myoglobin and cytochrome c) in order to obtain a value of Mr. O, oxidized cytochrome C550 , cytochrome C550 reduced with 1 mM ascorbate.

Figure 8 Effect of sample size on resolution of the bovine serum albumin-myoglobin pair. Sample concentration (A) 0.73mg/mL (O) 7.33mg/mL ( ) 73.3mg/mL. Column TSK G3000SW. Flow rate 0.5mL/min. (From Ref. 43.)...

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