Measurement of creatine kinase isoforms by agarose gel electrophoresis in the diagnosis of myocardial infarction.

To evaluate a method to quantitate the isoforms of serum creatine kinase isoenzyme MM (CK-MM) by agarose gel electrophoresis, sera of normal subjects (n = 74) and patients with acute myocardial infarction (n = 21) and other diseases (n = 67) were studied. The within-assay imprecision (CV) for CK-MM1, -MM2, and -MM3 was 1.9%, 0.8%, and 2.2% at the activity of 79, 105, and 64 U/L (30 degrees C, CK-NAC), respectively; while the assay-to-assay imprecision was 4.8%, 3.2% and 3.9%, respectively. The method could detect 5 U/L or more of any CK-MM isoform and was linear with respect to CK activity at values less than 1100 U/L. Sera from healthy subjects (n = 74) contained mainly CK-MM1 (mean = 48.5%), with lesser amounts of CK-MM2 (mean = 30.6%) and CK-MM3 (mean = 20.8%). The central 95-percentile reference range for the ratio of MM3/MM1 was 0.12-1.34 with mean = 0.49. The sensitivity of CK-MM3/MM1 ratio greater than 1.3 in the diagnosis of acute myocardial infarction employing the first available sample was 90% at a specificity of 91%, compared with a sensitivity of 81% and specificity of 87% for the conventional CK-MB assay. At CK-MM3/MM1 ratio of 1.6 or more, the specificity increased to 96% while sensitivity remained unchanged at 90%. This procedure for the quantitation of serum CK-MM isoforms is convenient, practical and suitable for inclusion in the routine panel of cardiac tests.     

Quantitative analysis for isoforms of creatine kinase MM in plasma by chromatofocusing, with on-line monitoring of enzyme activity

Changes in the proportions of individual isoforms of the MM isoenzyme of creatine kinase (CK; EC 2.7.3.2) in plasma promptly reflect both myocardial infarction and coronary recanalization. However, quantitative methods developed thus far are too slow or cumbersome for routine use in making clinical decisions. We report a convenient, quantitative chromatofocusing assay with on-line fluorometric detection of isoform activity in the column eluent that provides results within 40 min from the time of sample application. Sample eluted from a microbore chromatofocusing column (1.8-mL bed volume) is split between a reaction stream, into which CK reagents are added, and a reference stream. After incubation at 37 degrees C, NADPH formed by reaction of isoforms with CK reagent is detected at 340 nm. The system can detect activity of individual isoforms in plasma samples having total CK activity greater than or equal to 21 U/L (30 degrees C). Results correlated closely with those obtained by previously validated, but slow, chromatofocusing (r = 0.98, n = 30) and protein immunoblotting (r = 0.90, n = 20) procedures.     

Optimized preservation of isoforms of creatine kinase MM isoenzyme in plasma specimens and their rapid quantification by semi-automated chromatofocusing

We report a convenient chromatofocusing procedure for rapid and sensitive quantification of isoforms of the MM isoenzyme of creatine kinase (EC 2.7.3.2) in plasma and efficient methods for preserving isoform profiles during handling of specimens. The assay involves use of prepacked, re-usable Mono P chromatofocusing columns and a "Fast Protein Liquid Chromatograph" (FPLC) system with on-line detection of isoform enzymatic activity in column effluent. Profiles of isoforms are analyzed within 25 min with the use of a 1-mL column; the lower limit of sensitivity for CK activity is 5 mU, and recovery of each isoform is within 1% of the amount added to plasma. Collection of blood specimens in Vacutainer Tubes containing 28.5 mumol of EDTA (final concentration in plasma, 7 to 10 mmol/L) inhibited carboxypeptidase activity in plasma by 76%, sufficient to essentially abolish isoform conversion in vitro at room temperature. These methods should facilitate applications of isoform analysis for diagnosis of myocardial infarction and coronary artery recanalization.     

Serum isoforms of creatine kinase MM and MB in myocardial infarction. An appraisal of quantitative, clinical and pathophysiological information

Using an electrophoretic method, the changes in the catalytic activities of three CK-MM isoforms (MM1, MM2, MM3) and two CK-MB isoforms (MB1, MB2) in the serum of 13 patients with acute myocardial infarction (AMI) have been monitored for 3 days after the onset of chest pain. In post-AMI period, MM3 reaches a peak first, 17 h after infarction (394 U/l), followed by MB2 (17.3 h, 190 U/l), MB1 (20.6 h, 82 U/l), MM2 (28.7 h, 637 U/l), and MM1 (32 h, 780 U/l). According to their faster decay from circulation, MB2 and MM3 have higher fractional disappearance rates (-0.035 and -0.026 per hour, respectively). The MM3/MM1 activity ratio rises beyond the upper limit found in healthy subjects within about 3 h after onset of symptoms and peaks 9.3 h after AMI, even earlier than peaks of isoforms. These characteristics make the ratio an earlier and more sensitive indicator of acute enzyme release from necrotic myocardium.     

Serum creatine kinase MM isoforms in hypertrophic cardiomyopathy.

1. To determine whether a persistent release of creatine kinase from the myocardium occurs in patients with hypertrophic cardiomyopathy, the activities of serum creatine kinase MM isoforms were measured in 22 patients with hypertrophic cardiomyopathy and in 14 normal control subjects. 2. Serum creatine kinase MB activity was significantly higher in patients with hypertrophic cardiomyopathy (7.8 +/- 3.8 i.u./l) than in normal control subjects (0.4 +/- 0.8 i.u./l; P less than 0.01). 3. Serum MMa, MMb and MMc activities in patients with hypertrophic cardiomyopathy were 19.4 +/- 4.1%, 26.7 +/- 2.5% and 33.5 +/- 7.0% of the total creatine kinase MM activity, respectively. These values for each isoform were significantly different from those in normal control subjects (11.3 +/- 3.0%, 21.5 +/- 4.4% and 40.7 +/- 7.0%, respectively). The MMa/MMc activity ratio was significantly higher in patients with hypertrophic cardiomyopathy (0.61 +/- 0.25) than in normal control subjects (0.30 +/- 0.10; P less than 0.01). 4. Our results indicate that a small amount of the myocardial tissue isoform of creatine kinase MM (MMa) is constantly released in many patients with hypertrophic cardiomyopathy.     

Arginase in patients with breast cancer

The mean arginase activity in breast cancers (n = 80) was significantly higher than in control tissues and it accounted for 0.31 +/- 0.23 U/g wet tissue and 0.083 +/- 0.061 U/g (P < 0.05), respectively. With the cutoff value of 0.1 U/g wet tissue, raised arginase activity was observed in 74% of tumors. The preoperative arginase activity in blood serum from women with breast cancer was 11.2 +/- 7.9 U/l (n = 115), and it was significantly higher than in 70 healthy controls, where it was 5.7 +/- 2.4 U/l (P < 0.05). With the cutoff value for normal serum arginase activity above 8.0 U/l, the activity was raised in 10% of control individuals, and in 63% of women with breast cancer. The sensitivity and specificity of the arginase test in blood serum were 63% and 60%, respectively. Two isoforms immunologically identical to human kidney arginases (L-arginine amidinohydrolase) were found in both normal and cancerous breast tissues. The level of anionic form was similar in control and cancerous tissues, whereas the cationic isoform predominated in breast cancer. The cationic isoform was the only one present in serum of both ill and healthy women, and its level was higher in patients with breast cancer. Thus, it can be concluded that the cationic isoform is responsible for the increase of arginase activity in serum of patients with breast cancer.     

An immunochemical procedure for determination of creatine kinase 3(1) (serum-specific) isoform in human serum evaluated

Changes in the proportions of individual isoforms of creatine kinase (CK) in serum promptly reflect both myocardial infarction and coronary reperfusion. A new commercial kit has been introduced for measuring CK-3(1) isoform in serum (ISOFOR-MM, International Immunoassay Labs.). This is an immunochemical assay containing CK-3(1) specific monoclonal antibody, bound to magnetizable particles, used to immunoextract this isoform. The CK activity of the sample is measured before and after immunoextraction and the difference in the two values gives the measure of CK-3(1). Extraction of CK-3(1) was complete at less than or equal to 1200 U/L. Analysis of between-day imprecision gave CV between 2.9-7.9%. The method was not susceptible to interference by CK-3(2) and CK-3(3) isoforms, CK-2 isoenzyme, or mitochondrial CK. Reference interval for CK-3(1) (expressed as percent of total CK-3) was 42-69%. Correlation between percent CK-3(1) by isoform electrophoresis (x) and evaluated procedure (y) was y = 0.83x + 7.6, with r = 0.957 (n = 40). The ISOFOR-MM performed well enough in this evaluation to replace electrophoresis or isoelectric focusing for measurement of CK-3(1) isoform.     

Plasma purine nucleoside phosphorylase in cancer patients

BACKGROUND: Purine nucleoside phosphorylase (PNP) is the purine salvage enzyme that converts guanosine to guanine and inosine to hypoxanthine. METHODS: 279 samples from patients with differing cancers were collected during treatment at both pre- and post-dose stages for plasma PNP activity and compared with a normal population. RESULTS: Normal plasma PNP activity was found to be 3.2+/-1.4 U/l (n=55) as compared with the cancer patients (pre-dose 12.3+/-7.4 U/l [n=215] and post-dose 11.2+/-5.9 U/l [n=64]). Levels of plasma PNP did not differ greatly between the different cancer types but were on average four times greater than that found in the reference population.     

Most CD4+ T cells from human immunodeficiency virus-1 infected patients can undergo prolonged clonal expansion.

Time-dependent removal of the COOH-terminal lysine residue from each subunit of tissue MM creatine kinase by plasma carboxypeptidase N produces two additional isoforms that are readily separated, thereby permitting sensitive, early detection of acute myocardial infarction. Only two isoforms of MB creatine kinase have been detected in plasma leading to speculation that the COOH-terminal lysine on the B subunit is resistant to hydrolysis. To define the biochemical changes resulting in MB creatine kinase isoform conversion, we incubated highly purified MB creatine kinase from canine myocardium with plasma carboxypeptidase N. Quantitative anion-exchange chromatography of incubation mixtures and serial plasma samples from dogs subjected to coronary occlusion revealed a second, more acidic form evolved with time that was separated from the tissue isoform. Cyanogen bromide digestion of the two isoforms followed by amino acid sequencing of COOH-terminal peptides showed that MB creatine kinase undergoes removal of the COOH-terminal lysine residue from both M and B subunits. An intermediate form lacking lysine on the M subunit was delineated during incubations by the combined use of anion-exchange chromatography and conventional electrophoretic techniques. Thus, sequential cleavage of lysine from subunits of MB creatine kinase produces an intermediate isoform that has not been detected previously because of difficulties separating it from the tissue and fully converted isoforms.     

Increased plasma dihydroxyphenylalanine during sympathetic activation in humans is related to increased norepinephrine turnover

Plasma concentrations of dihydroxyphenylalanine (DOPA) were measured before and during isometric handgrip exercise or mental stress and after coffee drinking or intravenous infusion of desipramine to examine the influence of sympathetic nervous activity on DOPA formation. Sympathetic activity was assessed by the spillover of norepinephrine into plasma. Turnover of norepinephrine was assessed by the plasma concentration of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG). In normal subjects the resting plasma concentration of DOPA was 6.05 +/- 0.16 nmol/L (n = 42). Plasma DOPA level was increased by stimulation of the sympathetic nervous system; handgrip exercise caused a 0.49 +/- 0.07 nmol/L increase (n = 15), mental stress a 0.25 +/- 0.10 nmol/L increase (n = 34), and coffee drinking a 0.85 +/- 0.19 nmol/L increase (n = 9). Desipramine decreased plasma DOPA level by 0.25 +/- 0.06 nmol/L (n = 23). The small but consistent changes in plasma DOPA level during manipulations of sympathetic activity were positively correlated with changes in norepinephrine spillover (r = 0.55, n = 81) and plasma DHPG level (r = 0.66, n = 81). Percentage increases in plasma DOPA level during sympathetic activation were similar to those in plasma DHPG but were a sixth of the percentage increases in norepinephrine spillover. The similar increases in plasma DOPA and DHPG levels indicated that production of DOPA was related to the turnover of norepinephrine in sympathetic nerves. The smaller percentage increases in plasma DOPA (smaller than those in norepinephrine spillover) were consistent with the partial contribution of exocytotic neurotransmitter release to the turnover of norepinephrine in sympathetic nerves.     

Simultaneous automated measurement of serum total CK and CK-MM lsoform ratio in serum

We automated a two-step kinetic procedure for determining serum CK-MM isoform ratio using an immunoinhibition method. By measuring the total CK activity and the residual CK activity (serum CK-MM isoform) remaining after the inhibition by tissue CK-MM isoform specific monoclonal antibody reagent (CK-M01) the CKMM isoform ratio is calculated using the difference between total CK and residual CK activities divided by the residual CK activity. Linearities of total CK and residual CK assays were?7750 U/L and 2,500 U/L, respectively; within-run CVs of isoform ratio (N = 10) were 2.8 and 7.0% (mean 0.14 and 0.60), respectively. The MM³/MM¹ isoform ratio obtained with the proposed method (X) correlated well with the results of electrophoretic method (Y) according to the equation: Y = 0.98X ?0.3, r = 0.988. The normal reference range of isoform ratios obtained by assaying 1,222 serum samples from healthy subjects was 0.09–0.75. The isoform ratio increased after onset of chest pain, peaking at 2–6 hr thereafter. A mean isoform ratio of 1.86 was obtained with serum sample from 86 patients diagnosed as having an acute myocardial infarction (AMI). This method is accurate and highly sensitive, as the detection and early diagnosis of AMI can be completed in 10 min. © 1994 Wiley-Liss, Inc.     

Early detection of skeletal muscle injury by assay of creatine kinase MM isoforms in serum after acute exercise

We could detect skeletal muscle injury early after an acute exercise bout by measuring creatine kinase (CK, EC 2.7.3.2) MM isoforms in serum. Eleven men performed 120 alternating-arm, eccentric (muscle lengthening) biceps contractions with the intensity of each contraction being 110% of maximal concentric strength--a form of exercise previously shown to cause significant increases of CK in serum at 24 h and muscle soreness 48 h after exercise. Total CK and CK-MM isoform activities in serum were determined before and at 0.5, 0.75, 1, 1.5, 2, and 6 h after exercise. Using thin-film agarose gels and a rapid isoelectric focusing technique, we separated the MM isoforms into MM3 (skeletal muscle form), MM2, and MM1 (in vivo conversion forms). The isoforms reflected the MM form released into the serum from tissue as well as the conversion of one form to another. There were no significant increases in total CK from before to 6 h after exercise: 75 (SD 36) vs 91 (SD 33) U/L. However, CK MM3 in serum increased significantly (P less than 0.01) within 2 h after exercise from 22 (SD 6)% to 28 (SD 6)%. The MM3 to MM1 ratio also increased significantly (P less than 0.05) during this time, from 0.6 (SD 0.3) to 0.9 (SD 0.4). Thus, quantification of CK MM isoforms permitted very early detection of skeletal muscle enzyme release.     

Monoclonal antibody inhibiting creatine kinase MM3 but not isoform MM1

Monoclonal antibody CKM-G01 inhibited greater than 99% of the activity of porcine and human creatine kinase(CK)-MM isoenzyme purified from muscle. However, it inhibited only 54% of CK-MM in human serum. Chromatofocusing of serum CK-MM showed that CKM-G01 inhibited 100% of MM3 but not isoform MM1. CKM-G01 inhibited CK-MM2 by 57%. CKM-G01 specifically inhibited only the original CK-M subunit and not the subunit modified by removal of C-terminal lysine by carboxypeptidase N. CKM-G01 can be used for assay of CK isoforms. We devised a new diagnostic reagent involving it, which requires no analytical separation of isoforms, based on the immunoinhibition method, and applied it to early diagnosis of acute myocardial infarction. The "inhibition index," (inhibited CK activity/total CK activity) x 100, increased more rapidly than did total CK and CK-MB. Evidently this diagnostic reagent can be used for easy, early diagnosis of acute myocardial infarction.     

Creatine kinase isoforms in ischemic heart disease

The MM and MB isoenzymes of creatine kinase exist in serum as a collection of at least three major MM and two major MB isoforms. Each of these are derived from single tissue MM and MB isoforms, which are converted to these other forms by carboxypeptidase N after their release from necrotic skeletal and myocardial tissue. Measurement of the MM isoforms in ischemic heart disease is useful for early diagnosis of acute myocardial infarction and for the noninvasive determination of coronary artery reperfusion for infarction patients receiving thrombolytic therapy. Because MM is also released in acute skeletal-muscle disease, MB isoform measurements may have the highest clinical sensitivity. These determinations are important for providing objective information to cardiologists who need to make critical decisions concerning the management of these patients. I review the procedures for treating patients with myocardial infarction, the potential role of CK isoforms, and the methods currently available for isoform analysis, including high-resolution electrophoresis, isoelectric and chromatofocusing, and liquid chromatography. Rapid and highly sensitive methods are needed for implementation of CK-MM and MB isoforms for prospective emergency determinations for patients with acute myocardial infarction.     

Disposition of drugs in cystic fibrosis. I. Sulfamethoxazole and trimethoprim

The disposition of sulfamethoxazole and trimethoprim, after constant rate intravenous administration (10 mg/kg/hr sulfamethoxazole and 2 mg/kg/hr trimethoprim for 1 hour), was investigated in adult patients with cystic fibrosis (n = 7) and in age-matched healthy subjects (control subjects, n = 8). The total plasma clearance of sulfamethoxazole was found to be increased in cystic fibrosis (0.0262 +/- 0.0064 L/hr/kg) when compared with that found in control subjects (0.0188 +/- 0.0043 L/hr/kg). This increase in clearance was found to be primarily attributable to an increase in the metabolic clearance of sulfamethoxazole to N4-acetylsulfamethoxazole (0.00903 +/- 0.00247 versus 0.00355 +/- 0.00049 L/hr/kg) with the renal clearance of sulfamethoxazole remaining unchanged. These conclusions were not altered when the pharmacokinetic parameters were computed for the unbound drug or when they were normalized with respect to body surface area. These data indicate that, in cystic fibrosis, the enzymes mediating the metabolism of sulfamethoxazole to N4-acetylsulfamethoxazole, N-acetyltransferase(s), may be induced, activated, or both, or that the uptake of sulfamethoxazole by cells that metabolize sulfamethoxazole to N4-acetylsulfamethoxazole is enhanced. The total plasma clearance of trimethoprim was also found to be increased in cystic fibrosis (0.1808 +/- 0.0440 L/hr/kg) when compared with that found in control subjects (0.1139 +/- 0.0193 L/hr/kg). In contrast to sulfamethoxazole, this increase in clearance was found to be primarily attributable to an increase in the renal clearance of trimethoprim (0.1240 +/- 0.0299 versus 0.0720 +/- 0.0166 L/hr/kg). These data indicate that the tubular secretion of trimethoprim may be enhanced in cystic fibrosis.     

Reproducibility of plasma angiotensin-converting enzyme activity in human subjects determined by fluorimetry with Z-phenylalanine-histidyl-leucine as substrate

Despite the major physiologic role of angiotensin-converting enzyme (ACE), few studies have evaluated the ideal conditions for measuring human plasma ACE activity, specifically when using Z-phenylalanine-histidyl-leucine as substrate. This study, performed in volunteer patients, assessed the reproducibility of human plasma ACE activity measured by fluorimetry with Z-phenyl-histidyl-leucine as the substrate. After blood centrifugation, plasma was stored under different conditions until processing. The following sources of variability were evaluated: (1) the interval to centrifugation of blood after collection, (2) the temperature and (3) safe time for storing the plasma after cold centrifugation, (4) the effect of fasting. Plasma ACE activity was 20.6+/-7.7 U/mL, 20.9+/-8 U/mL, and 20.5+/-7.9 U/mL (n = 25) when samples were centrifuged immediately, after 1 hour of blood sampling, and after 3 hours of blood sampling, respectively (not significant). In plasma kept at -20 degrees C, ACE activity was not different after 1 week (17.4+/-4.3 U/mL) nor after 1 month (17.9+/-4 U/mL), whereas baseline ACE was 16.7+/-4.3 U/mL (n = 10). In plasma stored at -80 degrees C, ACE activity was 15.5+/-5.7 U/mL after 1 month (baseline 15+/-5.3 U/mL; not significant; n = 12). No evidence for hydrolysis of the reaction product of ACE (his-leu dipeptide) was observed in plasma samples kept for 1 month at -20 degrees C or at -80 degrees C (by high-performance liquid chromatography analysis). In plasma obtained before breakfast, ACE activity was 12.8+/-7.1 U/mL, and it was 12.3+/-7.5 U/mL 2 hours afterwards (not significant; n = 12). Thus, to determine human plasma ACE activity by fluorimetry with reliability, with Z-phenylalanine-histidyl-leucine used as a substrate, there is a safe interval of at least 3 hours before blood centrifugation at -4 degrees C. Plasma may be kept at -20 degrees C or at -80 degrees C for at least 4 weeks before final processing. Fasting does not influence its enzymatic activity.     

Hyperhomocysteinemia, paraoxonase activity and risk of coronary artery disease

OBJECTIVES: Paraoxonase-1 (PON1) detoxifies homocysteine thiolactone (HcyT) in human blood and could thus delay the development of atherosclerosis. We investigated (a) PON1 activity and polymorphisms, and (b) the relationship between PON1 activity, homocysteine (Hcy) and the severity of CAD patients in Tunisian population. DESIGN AND METHODS: We used PCR-RFLP analysis to detect the Q192R and L55M variants of the PON1 gene in 100 patients with CAD and in 120 healthy controls. Paraoxonase activity was measured spectrophotometrically using phenylacetate as a substrate. Total plasma homocysteine concentrations were determined by direct chemiluminescence assay. RESULTS: We found an increased Hcy level in CAD patients compared to the control group (15.86+/-8.63 vs. 11.9+/-3.25 micromol/L respectively, P<0.001), and a decrease in PON1 activity in CAD patients as compared to the control group (117+/-56 vs. 181+/-73 U/mL respectively, P<0.001). PON1 Q192R and L55M polymorphisms were not associated with the presence of CAD (P=0.592, P=0.294, respectively). However, we found that PON1 activity is lower with the PON1 192RR than with PON1 192QQ genotypes in the study population. Furthermore, there were no association between PON1 L55M polymorphism and PON1 activity. We showed a significant decrease in PON1 activity in CAD patients presenting 0- to 3-vessel stenosis (155+/-39; 135+/-36; 103+/-22; 77+/-24 U/mL, respectively; P<0.001). CONCLUSION: In this study, we showed that low PON1 activity is associated with the PON1 192RR genotypes and associated with the severity of CAD in the Tunisian population. We hypothesize that high level of Hcy together with low PON1 activity results in an increased plasma HcyT plasma concentration leading to protein N-homocysteinylation and the development and progression of atherosclerosis.     

Automated kinetic assay of angiotensin-converting enzyme in serum

We have developed and validated an automated kinetic method for angiotensin-converting enzyme (EC 3.4.15.1) on the Olli C + D analyzer, modified from that of Ronca-Testoni (Clin Chem 1983;29:1093-6) with N-[3-(2-furyl)-acryloyl]-L-phenylalanylglycylglycine used as substrate. We have determined appropriate reaction conditions for the assay, verified the principal analytical reliability criteria (repeatability, reproducibility, sensitivity), and established normal reference intervals (mean +/- SD) for the enzyme's activity, using serum of normal adults (100 +/- 35 U/L, n = 150), newborns (130 +/- 27 U/L, n = 10), women taking oral contraceptives (103 +/- 30 U/L, n = 10), smokers (109 +/- 38 U/L, n = 27), and patients with sarcoidosis (220 +/- 48 U/L, n = 15).     

Disposition of drugs in cystic fibrosis. III. Acetaminophen.

The disposition of acetaminophen after oral administration was investigated in adults with cystic fibrosis (n = 5) and in age-matched healthy control subjects (n = 5). The total plasma clearance of acetaminophen was found to be greater (p less than 0.025) in subjects with cystic fibrosis (0.362 +/- 0.081 L/hr/kg) than in control subjects (0.247 +/- 0.022 L/hr/kg). This difference in clearance was found to be primarily attributable to a greater metabolic clearance of acetaminophen to acetaminophen sulfate (0.080 +/- 0.023 L/hr/kg for subjects with cystic fibrosis and 0.045 +/- 0.008 L/hr/kg for control subjects; p less than 0.05) and to a greater metabolic clearance of acetaminophen to acetaminophen glucuronide (0.189 +/- 0.051 L/hr/kg for subjects with cystic fibrosis and 0.114 +/- 0.017 L/hr/kg for control subjects; p less than 0.05) in persons with cystic fibrosis. Of the mechanisms that may be responsible for these differences, the most likely is enhanced activity (in subjects with cystic fibrosis) of the transferases that mediate the metabolism of acetaminophen to acetaminophen sulfate and acetaminophen glucuronide, respectively.     

Elevated serum CK-BB levels in patients with cerebral transtentorial herniation after ischemic stroke

We examined the time course of CK and its isoenzymes in 15 patients with severe ischemic stroke. Patients with cerebral transtentorial herniation (n = 7) had the highest CK-BB activity during herniation (1.54 +/- 0.6 U/L, mean +/- SD; range: 1.0-2.6 U/L). These values were distinctly above the values of a control group of 20 patients with non-neurological diseases (0.39 +/- 0.2 U/L, mean +/- SD). In patients with smaller lesions without herniation (n = 8) the maximum CK-BB increase was lower (0.56 +/- 0.26 U/L, mean +/- SD).