The analytical and clinical performances of the new fluorescent immunoassay (CK-MB mass Vidas-BioMerieux) were examined and compared to the chemiluminescent test (CK-MB mass Access-Sanofi-Pasteur). Assay precisions of the CK-MB Vidas test within-assay or between-assay were less than 5.4 and 5.3%, respectively. Linearity was tested up to 214 microg/L. The CK-MB Vidas test was free of interference with CK-BB, CK-MM, and macro-CK. One hundred nineteen blood samples from patients with ischemic myocardial injury (IMI): acute myocardial infarction (AMI), suspected myocardial contusion (SMC), and unstable angina pectoris (UA), were tested using both immunoassays. In AMI, a good correlation was found (Y [CK-MB Access] = 1.1372 x [CK-MB Vidas] - 6.3902; r(2) = 0.96). In UA and SMC, low values were observed and both methods were well correlated (Y [CK-MB Access] = 1.3662 x [CK-MB Vidas] + 0.0671; r(2) = 0.97). Clinical data were in good agreement with both immunoassays. ROC analysis performed in AMI demonstrated that the clinical performances of the two assays were similar.

UNASSIGNED

To study the clinical effect of ganglioside (GM) and fructose-1, 6-diphosphate (FDP) on neonatal heart and brain injuries after asphyxia.

UNASSIGNED

Ninety-one neonates with asphyxia neonatal heart and brain injuries were randomly divided into an observation group and a control group. Both groups were given symptomatic treatment as soon as possible. On this basis, the observation group was given 200 mL of 5% glucose injection and 20 mg of GM and 250 mg/kg·d FDP by intravenous infusion. The above two drugs were given once a day for 14 days. The control group was given 20 mL of 5% glucose injection, 2 mL of cerebrolysin and 250 mg/kg·d FDP by intravenous infusion, once a day for 14 days. Both groups were administered on the first day after admission, and the course of treatment was 14 days. The treatment outcomes of the two groups were compared by detecting the levels of glycogen phosphorylase isoenzyme BB (GPBB), cTn-I and CK-MB, MRI results and Neonatal Behavioral Neurological Assessment (NBNA) scores before and after treatment.

UNASSIGNED

The levels of GPBB, cTn-I and CK-MB in the observation group were significantly higher than those of normal neonates. After treatment, the levels of cTn-I and CK-MB in the observation group were closer to those of normal neonates compared with the control group, with significant differences (P<0.05). There was a significant difference in the brain MRI examination between the two groups (P<0.05). The NBNA scores of the two groups were significantly different before and after treatment (P<0.05). The total effective rate of the observation group was significantly higher than that of the control group (P<0.05).

UNASSIGNED

Neonatal heart and brain injuries after asphyxia can be well treated by combining GM with FDP.

It has been suggested that perinatal asphyxia is not generally followed by neurological impairment unless there is preexisting chronic fetal distress. In cases of brain damage one can observe elevated levels of CK-BB. The purpose of our study was to evaluate CK isoenzymes in umbilical cord blood sera of newborns affected by chronic fetal distress. Fetal distress reflected by placental dysfunction was characterized by a diminished HPL level and decreased activity of CAP. We estimated CK isoenzymes with the use of DEAE-sepharose CL-6B column chromatography. Total CK activity was measured using kits supplied by Boehringer-Mannheim (Monotest CK-NAC aktiviert). The clinical state of examined newborns was estimated. Investigations were carried out in the group of 57 infants delivered after 37 weeks of gestation. Total CK activity in cord sera ranged from 40 to 400 U/l. Our results showed a significant rise of CK-BB activity in cord sera of newborns delivered from pregnancies with placental dysfunction (figure 2) as well as in cases of asphyxiated infants (figure 3). We were unable to demonstrate differences in total CK, CK-MM and CK-MB activities in all examined groups of newborns. Other authors have confirmed that severe asphyxia results in increase in CK-BB activity in cord blood. Infants with ominous fetal heart rate patterns have higher CK-BB activity. There are several possible sources for CK-BB activity in umbilical cord blood sera, i.e. fetal brain, lung, gastrointestinal tract, placenta and uterus. It appears that the brain is most likely the source of elevated CK-BB activity found in cord blood in cases of placental dysfunction.

The effect of gastrointestinal surgery on serum creatine kinase activity was studied in 30 patients. The MB isoenzyme was demonstrated in sera of 30% of the patients and BB isoenzyme in 23%. MB content varied from 0.8 to 10.3% of the total creatine kinase activity, and the BB content from 0.6 to 18.4%. The CK-BB was probably of gastrointestinal origin, since gastrointestinal tract contains high CK activity with BB isoenzyme predominating. A cardiac origin for the observed serum CK-MB isoenzyme increase would seem the most likely, although no patients showed evidence of electrocardiographic changes. Increased CK-MB activity has been observed in myocardial ischaemia without infarction.

I assessed the effect of therapeutic hypothermia on the activity in cerebrospinal fluid of creatine kinase (EC 2.7.3.2) and its brain isoenzyme (CK-BB), lactate dehydrogenase (EC 1.1.1.27), and aspartate aminotransferase (EC 2.6.1.1.) as markers of cerebral damage in patients with transient anoxic-ischemic brain injury. Moderate hypothermia (30-32 degrees C) lasting more than 24 h resulted in disproportionately greater activity of creatine kinase during the post-insult period than in patients not treated with hypothermia but having similar insults and outcome (p less than .01 for survivors, and p less than .005 for nonsurvivors). No differences were observed for the thermostable enzymes lactate dehydrogenase and aspartate aminotransferase, which demonstrates that the effect of hypothermia must be taken into account when thermolabile enzymes are used as sole markers of brain damage in such patients.

CPK-BB (CK-BB) isoenzyme is an intracellular enzyme released in various neurologic conditions, including central nervous system (CNS) infections. Activity of CK-BB in cerebrospinal fluid (CSF) was determined in 80 children by electrophoresis and densitometry. The possible correlation between CNS infection and CK concentrations was assessed. Significantly elevated concentrations of CK activity (P < 0.01) in the CSF were found in children with bacterial meningitis as compared with children with either aseptic meningitis or normal CSF findings. The data suggest the possibility of utilizing CSF CK activity to differentiate between bacterial and viral meningitis in situations where a routine CSF examination is inconclusive.

Macro creatine kinase (CK, EC 2.7.3.2) and macro lactate dehydrogenase (LD, EC 1.1.1.27) were both present in the serum of a 70-year-old woman with myocardial infarction. This interfered with the interpretation of the CK and LD isoenzyme analyses. Gel filtration and immunoprecipitation showed that the macro CK consisted of IgG and CK and the macro LD of IgG and LD. The IgG in this patient bound both MB and BB isoenzymes of CK, resulting in a macro CK complex that co-migrated with CK-MM on cellulose acetate electrophoresis. This situation led to a falsely negative laboratory diagnosis for myocardial infarction.

Serum creatine kinase isoenzymes were studied in 41 patients suffering from Duchenne type muscular dystrophy and 20 mothers of patients (carriers) by cellulose acetate electrophoresis. Both the MM and MB types were found in all cases of Duchenne type dystrophy patients, and in carriers with highly elevated total creatine kinase activity BB was not observed above the detection limits of the methods used. However, a so-called atypical CK--BB band has been demonstrated.

Serum neuron-specific enolase (NSE) and serum creatine kinase isoenzyme BB (CK-BB) were measured in 43 small cell lung cancer (SCLC) patients. The overall sensitivity of NSE (greater than 12.5 ng/ml) was 65%; in limited disease (LD) 48% and in extensive disease (ED) 100%. CK-BB was detected in 14 patients (32%); the sensitivity was 17% in LD and 64% in ED. During treatment NSE declined or stabilized to normal level in LD together with objective response in 75% (21/28), and rose again with progression in 28% (6/21). CK-BB fell to normal in all 5 patients with LD, in 3 of them with objective response. In ED elevated NSE and CK-BB declined to normal with objective response in 73% (8/11) and in 25% (2/8) of the evaluable patients respectively. We conclude that serum NSE is a potential marker for staging and response monitoring in SCLC, but that CK-BB gives additional information of limited value.

Cultured human skin fibroblasts from 9 patients with Duchenne muscular dystrophy (DMD) and 8 normal age- and sex-matched controls were examined for creatine kinase (CK) activity. Both the normal and the DMD fibroblasts were found to have significant levels of CK activity (approximately 10 x 10(-3) IU per milligram of fibroblast protein). The control cells had slightly higher CK activity than the DMD lines, but this difference was not significant (0.2 less than P less than 0.1). The MM (muscle) isozyme, the BB (brain) isozyme, and the MB (hybrid) isozyme, of CK were found to be present in fibroblasts. The isozymes were separated by electrophoresis and the relative amount of each was determined for both normal and DMD cells. In normal fibroblasts, approximately 48% of the total CK activity was of the MM type, 40% was of the BB type, and 12% was of the MB type with no significant differences apparent between normal and DMD groups. The presence in human fibroblasts of significant levels of CK activity with a characteristic isozyme profile is an important consideration for studies of this "marker" enzyme in the pseudohypertrophic muscle of DMD.

The rapid stimulation of the specific activity of the brain type isozyme of creatine kinase (CK BB) is an almost universal marker of cell stimulation. We have studied its stimulation in skeletal-derived cells and shown that the increase in its activity is closely correlated with the biochemical parameter of cell proliferation - [(3)thymidine incorporation into DNA - and with the morphological parameters of bone growth, increase in thickness of cortical bone and of the number of cells in the proliferating zone of the epiphyseal growth plate. We have used the increase in CK activity to demonstrate sex specific stimulation of diaphyseal bone, exclusively by estrogens in females and by androgens in males, and the dependence of sex steroid stimulation on an adequate level of vitamin D. After finding that parathyroid hormone can act as a mitogen via a phospholipase-C-phosphoinositide turnover pathway, we collaborated with colleagues at the GBF in Braunschweig to find that mid-region fragments of PTH could act exclusively as mitogens, without stimulating cAMP production leading to bone resorption. hPTH (28-48) variants designed to be resistant to proteolysis were efficient in stimulating CK specific activity in vitro and in vivo and increased cortical bone thickness and the number of proliferating epiphyseal cartilage cells in rat long bones. These results are put into an historical context and compared with recent studies, in this short, selective review.

The author measured blood concentrations of aldosterone, epinephrine, norepinephrine, and creatine kinase isozyme (brain type) (CK-BB) in 65 patients with hypertensive intracerebral hemorrhage. The purpose of this study was to evaluate these measurements in determining the severity of acute cerebral damage in such patients. There were 42 males and 23 females ranging in age from 30 to 93 years. Their clinical status was classified as mild or severe on the basis of neurological grading. In the mild group, plasma aldosterone increased slightly at the onset of disease, while the other markers showed no change. In contrast, the severe group showed elevation of all markers on admission, with a gradual return to normal by day 3 to day 7 of hospitalization. Analysis of the data by hematoma site revealed that aldosterone levels increased in patients with thalamic hemorrhage; epinephrine and norepinephrine concentrations were high in those with pontine hemorrhage; and CK-BB levels were elevated in cases of thalamic and cerebellar hemorrhage. It was also noted that patients in whom all four markers were increased tended to have poor outcomes.

A simultaneous two-site immunoenzymometric assay for creatine kinase MB determination (Hybritech Tandem-E CK-MB) using monoclonal antibodies was evaluated and compared with cellulose acetate electrophoresis using fluorometric scanning densitometry. The assay has satisfactory precision (between-day analysis gives a coefficient of variation between 2.1 and 9.4%) and is not susceptible to interference by concentrations of creatine kinase MM up to 5000 micrograms/l (3400 U/l) and creatine kinase BB up to 1000 micrograms/l (1085 U/l). The upper limit of MB isoenzyme concentration in 250 apparently healthy people was 5.5 micrograms/l. Comparison between the immunoenzymometric assay (y) and electrophoresis (x) yielded the following linear regression equation: y = 0.37x + 1.9, with a correlation coefficient of 0.828. The characteristics of the temporal kinetics of MB isoenzyme, calculated by two methods, in 49 patients with acute myocardial infarction, were nearly identical in terms of the rate of creatine kinase MB release and the time at which the peak value is obtained, but not in terms of the rate of elimination of the isoenzyme. The fractional disappearance rate of MB isoenzyme from the circulation was significantly higher if calculated with Tandem-E results rather than with electrophoresis results (-0.035 vs -0.028, p less than 0.001). Whereas in the first day after infarction immunoenzymometric assay and electrophoresis had the same clinical sensitivity for identifying patients with acute myocardial infarction, in specimens collected more than 24 hours after the onset of the chest pain, the clinical sensitivity of the immunoenzymometric method was lower. Our results show that it is still premature to draw definitive clinical conclusions from the immunoassay results.

Type II autosomal dominant osteopetrosis (ADO2) is an inherited disorder characterized by increased skeletal mass and characteristic abnormalities evident on radiography. Although previous investigators have described nonpenetrant individuals (carriers), it is not known whether carriers manifest subtle abnormalities. We hypothesized that ADO2 carriers would have an abnormality of osteoclast function that would lead to changes in bone mineral density (BMD), in serum tartrate-resistant acid phosphatase (TRAP), or in creatine kinase isoenzyme BB (CK-BB) levels that would permit carrier recognition. We identified a female carrier in a well-established ADO2 family and measured BMD, serum TRAP, and CK-BB concentrations. She had normal BMD, serum TRAP, and CK-BB concentrations. Thus, these measurements cannot be used to exclude carrier status in individuals who are seen for genetic counseling. However, measurements in other asymptotic carriers are necessary before concluding that these measurements are normal in all or most nonpenetrant individuals.

Incubation of CK-BB in serum (1:3, v/v) at 37 degrees C for 3 h caused a change of its electrophoretic mobility and decay of its catalytic activity. Similar effects were observed following incubation in water. Incubation in saline somehow preserved the electrophoretic mobility but not the catalytic activity. No effect was noted when incubated at 4 degrees C for 3 h. Further study on the rate of decay revealed that the decay in albumin solution (1:50, v/v) is quite similar to that in serum. More dramatic decay was noted when incubated in water and less when incubated in saline. It was further shown that the higher the incubation temperature (4 degrees C, 25 degrees C or 37 degrees C) the faster the decay. The rate of decay of CK-MM was much slower in all conditions of incubation. Determination of isoenzyme activities by means of an immunoprecipitation method again demonstrated that CK-BB lost a great deal of its catalytic activity following incubation at 37 degrees C for 1 h, and hence falsification of the isoenzyme pattern.

1. A CK(BB) fraction was observed in sera of a patient with prostatic carcinoma. The fraction accounted for 59% of the total enzyme activity. A metastatic tumor of a prostatic carcinoma was observed to contain solely the CK(BB) isozyme. An embryonal testicular carcinoma was observed to have a higher percentage of the CK(BB) fraction when compared to the adjacent tumor free testicular tissue in a third patient. These studies suggested that in certain carcinomas there are tissue isozyme modifications at the molecular level. The isozymic modification was suggested as a reversion towards an embroyonic pattern as the adult molecular form tended to disappear while the fetal form increased. This too suggests that the isozymes of CK may be a useful model in elucidating the mechanism through which this transition occurs. 2. The high percentage of CK(BB) in the sera of the patient with metastasis was discussed. The origin could not be determined, but either a primary tumor or a metastatic tumor by their enzyme modifications could account for this increased fraction in sera.

The early effect of estrogen on the synthesis of cytosolic proteins was investigated in the luminal epithelium, endometrial stroma and myometrium of the uterus in adult ovariectomized rats. The procedure of Reiss and Kaye (1981) was followed (involving two-step fractionation of 35S-labelled proteins and fluorographic analysis) except that the uteri were fractionated into their three main tissue components before homogenization. The results show that E2 stimulates the synthesis of BB-CK (brain-type creatine kinase), the major component of IP (estrogen-induced protein), in the three tissues. This suggests that BB-CK is related to a function that is common to the estrogen responses (such as hypertrophy) of all three uterine tissues in ovariectomized adult animals. The synthesis of two unidentified proteins of 37000 and 27000 Mr was markedly stimulated in the epithelium. These proteins are probably rate-limiting in responses to estrogen treatment that are specific to the epithelium. The 27000 Mr protein has the same charge as that of the 27000 Mr nafoxidine-induced protein described previously (Mairesse et al., 1981) and is probably therefore the same protein.

This patient, on admission, presented with a tentative diagnosis of myocardial infarction: the electrocardiogram showed a nonspecific ST-segment and T-wave abnormalities, and total creatine kinase (CK; EC 2.7.3.2) activity was slightly increased (238 U/L). However, a high electrophoretic value for CK-MB (50% of total CK activity) and the electrophoretic pattern of lactate dehydrogenase (EC 1.1.1.27) isoenzymes ruled out myocardial infarction. The isoenzyme migrating as CK-MB was found later to contain no immunologically normal CK-M subunits, and it was bound to IgA. A mixture of the patient's serum and a human serum control containing all CK isoenzymes showed altered electrophoretic mobility only for CK-BB, indicating that the patient's serum contained antibodies to the B unit of CK. Elution from a Sephadex G-200 column showed that the peak at which most of the anodic CK was eluted corresponded to a molecular mass of approximately 200 kDa. Evidently this atypical isoenzyme was an IgA-CK-BB complex. Because this macro CK type 1 can mimic CK-MB, it may therefore be a source of confusion.

Increased creatine kinase isoenzyme BB (CK-BB) has been observed in sera from patients with brain injuries and occasionally in sera from patients with malignancy. We report here that, in two patients with giant cell tumor of bone (GCT), preoperative serum CK-BB increased to approximately 20 and 90 U/L, but in postoperative serum the CK-BB decreased to normal values. That the tumors contained CK-BB was indicated by electrophoretic analysis and immunohistochemical staining. Furthermore, serum CK-BB was detectable in five additional cases of GCT and in cultured tumor cells from a patient with GCT by an electrophoretic method. These results suggest that CK-BB may be a marker for GCT.

Hypertrophy in hypertensive hearts is associated with increased risk of cardiac morbidity and mortality that is not characteristic of exercised hearts. This study was done to determine whether exercise training of normotensive and borderline hypertensive rats induces the increased myocardial expression of BB and MB isoforms of creatine kinase (CK) that characterizes hypertensive hypertrophy. Spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats were subjected to either an 8% sodium chloride diet or swim training to produce myocardial hypertrophy. Both exercise and a high salt diet induced an increase in the combined expression of CK-MB and CK-BB in SHR after 2 months. However, since swimming also exacerbated hypertension in SHR, exercise induced effects on CK were not distinguishable from those of hypertension. In WKY, neither exercise nor a high salt diet induced significant changes in CK isozyme expression. In BHR fed a high sodium chloride diet, significant increases in mean arterial pressure and left ventricular weight to body weight were not associated with changes in CK expression. In contrast, following 10 months of swim training BHR exhibited mild hypertrophy, decreased resting heart rates, and an increase in the combined expression of CK-MB and CK-BB. Therefore, exercise associated with a cardiac training effect in BHR induced changes in CK isozyme expression similar to those in hypertensive hearts.

Creatine kinase (CK) isoenzymes, total and specific CK activities and protein concentrations were measured in the cultured cells from muscle biopsies of 18 carriers of Duchenne muscular dystrophy (DMD) and the results compared with those in the cultures of patients with DMD and other neuromuscular disorders. The proportion of MB and BB isoenzyme in the carriers was similar to that in boys with DMD and in patients with other myogenic disorders, and significantly different from neurogenic patients. CK isoenzyme analysis appears to be a more sensitive index of in vitro differentiation than estimation of CK activities. Cell differentiation is reduced and the incidence of cell death increased in cultures derived from needle rather than open biopsies.

It has recently been claimed that an increase in creatine kinase isoenzyme BB(CK-BB) in cerebrospinal fluid (CSF) is well correlated with the cerebral outcome in patients resuscitated after cardiac arrest. Twenty-one such patients consecutively admitted from outside this hospital participated in the study. The patients were divided into two groups: 6 survivors and 15 nonsurvivors. The median CSF-CK-BB value was 5 U/L among nonsurvivors and below detection limit among survivors (NS). However, the predictive value of a positive test is limited, since only 6 of 15 nonsurvivors (40%) had an increase in CSF-CK-BB (predictive value of positive test = 67%). The predictive value of a negative test is limited, since 3 of 6 survivors (50%) showed no rise in CSF-CK-BB (predictive value of negative test = 25%). No relationship between cerebral dysfunction and CSF-CK-BB values was revealed. Thus, CSF-CK-BB does not predict the clinical outcome in patients resuscitated after cardiac arrest.