Evaluation of the cephalometrics modification of growing Class II Division I patients after treatment with the PUL appliance: a pilot study.

AIM: The aim of this preliminary study was to evaluate short-term dentoskeletal changes obtained with a functional appliance for Class II Division I malocclusions called propulsor universal light (PUL). METHODS: Fifteen Class II Division 1 patients (10.6±1.2 years) were consecutively treated by one expert operator with PUL appliance and they were compared with a longitudinal group of Class II Division I untreated patients (9.9±1.9 years) matched for pubertal growth spurt stage and sex. Lateral cephalograms were taken before PUL therapy and at the end of treatment. The mean duration of treatment was 11.2±0.3 months; t-test or Mann-Whitney U-test was used (P <0.05). RESULTS: Statistically significant reduction of the overjet, WITS and ANB was noticed in treated group as well as a significant improvement of CoGo and Ramus. CONCLUSION: Class II Division I malocclusion in the short term was efficiently treated by PUL appliance with both skeletal and dentoalveolar changes.

Different biological behaviour of Waldenström Macroglobulinemia in two dogs.

Waldenström Macroglobulinemia is a low-grade immunosecretory disorder associated with lymphoid tumours, which is rarely reported in veterinary medicine. In this study, we describe two clinical cases of this rare syndrome in dogs, each characterized by a different onset and clinical course. In one case, a hyperacute onset and aggressive behaviour of the neoplasm was observed. Absolute serum viscosity (SV) was retrospectively evaluated in order to explain clinical findings. Rotational viscosimetry showed good precision in measuring SV. Both dogs had SV values higher than a control groups of healthy dogs although only one subject developed hyperviscosity symptoms and complications. At high paraprotein concentrations, a slight reduction of the M-component was associated with a marked decrease in SV. Thus, this work suggests that SV assessment is a relevant tool for managing monoclonal gammopathies, whose usefulness should be further confirmed in larger cohorts of dogs.

Creatine kinase, myosin heavy chains and magnetic resonance imaging after eccentric exercise.

The aim of this study was to examine the relationship between myosin heavy chain (MHC) release as a specific marker of slow-twitch muscle fibre breakdown and magnetic resonance imaging (MRI) of skeletal muscle injury after eccentric exercise. The effects of a single series of 70 high-intensity eccentric contractions of the quadriceps femoris muscle group (single leg) on plasma concentrations of creatine kinase and MHC fragments were assessed in 10 young male sport education trainees before and 1 and 4 days after exercise. To visualize muscle injury, MRI of the loaded thigh was performed before and 4 days after the eccentric exercise. All participants recorded an increase (P < 0.05) in creatine kinase after exercise. In five participants, T2 signal intensity was unchanged post-exercise compared with pre-exercise and MHC plasma concentration was normal; however, they showed an increase (P < 0.05) in creatine kinase after exercise. For the remaining five participants, there was an increase in T2 signal intensity of the loaded vastus intermedius and vastus lateralis. These changes in MRI were accompanied by an increase in MHC plasma concentration (P< 0.01) as well as an increase in creatine kinase (P < 0.01). We suggest that changes in MRI T, signal intensity after muscle damage induced by eccentric exercise are closely related to damage to structurally bound contractile filaments of some muscle fibres. Additionally, MHC plasma release indicates that this damage affects not only fast-twitch fibres but also some slow-twitch fibres.

Release of muscle proteins after downhill running in male and female subjects.

The release of muscle proteins after downhill running, which mainly includes eccentric muscle action, was compared in females (F; n=9) and males (M; n=9). They performed 20 min of downhill treadmill running with 16% decline with a target heart rate of 70% of the individual VO2peak, which was determined two weeks before. Blood samples were drawn before, 6 and 24 h after exercise to measure plasma levels of skeletal troponin I (sTnI), myosin heavy chain fragments (MHC), creatine kinase (CK), and myoglobin (Mb). Baseline levels before exercise were significantly higher in males compared to females for the cytoplasmic proteins CK and Mb, but the difference for MHC and sTnI was not significant. Both groups displayed marked and significant early (6 h) increases (P<0.05) for sTnI (median: F: 8.2 microg/L; M: 22.0 microg/L), Mb (median: F: 86.8 microg/L; M: 407 microg/L), and CK (median: F: 162 U/L; M: 339 U/L). A significant (P<0.05) but delayed (24 h) increase was found for MHC (median: F: 482 microU/L; M: 651 microU/L). The absolute values for all four parameters were significantly (P<0.05) higher in males compared to females; however, no difference was found for the relative increases and the time course of all parameters between females and males. We conclude 1) that there were no significant differences in the basal concentrations of predominantly bound proteins, and 2) that there were no differences in the relative muscle protein release between females and males before and after one bout of high-intensive eccentric exercise. The higher plasma concentrations of all measured muscle proteins in males are probably caused by the higher muscle mass compared to females.

Antigenic definition of cardiac troponin I.

The presence of cardiac troponin I in the serum is now considered as one of the most specific biochemical markers of acute myocardial infarction. To improve the knowledge of the antigenic properties of cardiac Troponin I, a set of monoclonal antibodies and polyclonal antibodies against human cardiac troponin I has been tested with overlapping peptides covering the cardiac troponin I sequence. The results indicate that N-terminal and C-terminal cardiac troponin I regions were most often recognized by poly- and monoclonal antibodies. These observations are valuable for choosing the best combination of monoclonal antibodies to set up new immunoassays to detect serum cardiac troponin I earlier after myocardial damage, to understand better which forms are released, and finally to propose appropriate cardiac troponin I standards.

Human cardiac troponin I: precise identification of antigenic epitopes and prediction of secondary structure.

The presence of human cardiac troponin I (hcTnI) in serum is considered to be a highly specific biochemical marker of acute myocardial infarction. To better understand the antigenic properties of hcTnI, a set of 68 overlapping peptides covering the complete amino acid sequence of hcTnI was prepared and used in epitope mapping experiments. All 16 anti-hcTnI monoclonal antibodies tested were found to recognize a peptide epitope, indicating that recognition by anti-hcTnI monoclonal antibodies was not dependent on the tertiary structure of the protein. Furthermore, the peptide reactivity with anti-hcTnI polyclonal antibodies indicated that most of the sequence of the protein was antigenic; in particular, the N- and C-terminal extremities were found to be the strongest antigenic regions. By using accurate secondary structure prediction methods, hcTnI was found to be an all-alpha type protein, with five regions predicted as helices. Matching the results of the epitope analysis with the structural prediction led us to the view that hcTnI is not a globular protein but probably adopts an extended conformation, allowing a large part of the amino acid sequence of this molecule to be recognized by the immune system. This improved knowledge of the antigenic and structural properties of hcTnI may help in developing new antibodies and immunoassays for use in diagnosing myocardial infarction.

Circulating cardiac troponin I in severe congestive heart failure.

BACKGROUND: Spontaneous progression of severe congestive heart failure is structurally characterized by cellular degeneration and multiple foci of myocardial cell death. The cardiac muscle isoform of troponin I is uniquely expressed in the adult human myocardium, and an increase in its circulating levels is highly indicative of myocardial injury. Accordingly, we addressed the usefulness of cardiac troponin I as a sensitive and specific molecular marker of congestive heart failure in patients with severely reduced left ventricular performance. METHODS AND RESULTS: A new generation single-step immunoenzymoluminometric assay with high analytical sensitivity was used to assess cardiac troponin I in patients with severe congestive heart failure, healthy blood donors, and hospitalized control subjects without known cardiac disease. The cardiac troponin I concentration (mean+/-SEM) was 72.1+/-15.8 pg/mL in heart failure patients and 20.4+/-3.2 and 36.5+/-5.5 pg/mL in healthy and hospitalized control subjects, respectively (P<.01 versus heart failure patients). When both control groups were considered, the mean cardiac troponin I level was 25.4+/-2.9 pg/mL (P<.01 versus heart failure patients). Creatine kinase MB mass and myoglobin concentrations remained within the normal range in all groups. CONCLUSIONS: These data (1) provide the first evidence for ongoing myofibrillar degradation and increased cardiac troponin I levels in patients with advanced heart failure and (2) show potential usefulness of cardiac troponin I as a specific and sensitive new serum marker molecule in severe congestive heart failure.

Skeletal troponin I as a marker of exercise-induced muscle damage.

The utility of skeletal troponin I (sTnI) as a plasma marker of skeletal muscle damage after exercise was compared against creatine kinase (CK), myoglobin (Mb), and myosin heavy chain (MHC) fragments. These markers were serially measured in normal physical education teacher trainees after four different exercise regimens: 20 min of level or downhill (16% decline) running (intensity: 70% maximal O2 uptake), high-force eccentric contractions (70 repetitions), or high-force isokinetic concentric contractions of the quadriceps group (40 repetitions). Eccentrically biased exercise (downhill running and eccentric contractions) promoted greater increases in all parameters. The highest plasma concentration were found after downhill running (median peaks: 309 U/l CK concentration (-CK-)), 466 microgram/l Mb concentration (-Mb-), 1,021 microU/l MHC concentration (-MHC-), and 27.3 microgram/l sTnI concentration ([sTnI]). Level running produced a moderate response (median peaks: 178 U/l -CK-, 98 microgram/l -Mb-, 501 microU/l -MHC-, and 6.6 microgram/l [sTnI]), whereas the concentric contraction protocol did not elicit significant changes in any of the markers assayed. sTnI increased and peaked in parallel to CK and stayed elevated (>2.2 microgram/l) for at least 1-2 days after exercise. In contrast to MHC, sTnI is an initial, specific marker of exercise-induced muscle injury, which may be partly explained by their different intracellular compartmentation with essentially no (MHC <0.1%) or a small soluble pool (sTnI: median 3.4%).

Cardiac troponin I in patients with hematologic malignancies.

BACKGROUND: The cardiac isoform of troponin I (cTnI) is a myofibrillar protein highly specific for myocardial injury. We used a recently developed new-generation immunoassay with high analytical sensitivity to measure cTnI in patients diagnosed with hematologic malignancies, before chemotherapy and after an intermediate cumulative dose of anthracyclines. We hypothesized that measurement of cTnI with this sensitive method would provide evidence of myocardial injury in these patients. METHODS: Sera from 115 individuals (60 healthy controls, 25 anthracycline-naive patients and 30 patients treated with intermediate cumulative doses of anthracyclines) were assessed for cTnI, creatine kinase MB (CKMB) mass and myoglobin. Radionuclide left ventricular ejection fraction (LVEF) was also determined. RESULTS: Using this sensitive assay, detectable concentrations of cTnl were measured in the healthy population [mean, 19.5 pg/ml, 95% confidence interval (CI) 13.5-25.5 pg/ml]. Anthracycline-naive patients had cTnI mean values (36.5 pg/ml, 95% CI 25.1-47.9 pg/ml) that were significantly (P < 0.01) greater than those in the control group. cTnI was significantly (P < 0.00001) increased in anthracycline-treated patients (76.4 pg/ml, 95% CI 67.0-85.8 pg/ml) compared with both the anthracycline-naive patients and the controls. CKMB, myoglobin and LVEF were within the normal range in all patients. CONCLUSIONS: These data provide evidence for cardiac involvement in patients with hematological malignancies before and during the course of anthracycline chemotherapy. They suggest that detection of myocardial injury may be facilitated by measurement of cTnI with a highly sensitive assay.

Epitope localization of monoclonal antibodies used in human troponin I immunoenzymometric assay.

Serum troponin I isoforms have proven to be potent markers of striated muscle injury. They reach the blood-stream soon after their liberation from the damaged muscular cell and can be detected by the use of selected antibodies. Among monoclonal antibodies (MAbs) originally produced against cardiac troponin I (cTnI), two MAbs able to cross react with the skeletal isoform of troponin I (sTnI) were selected and used to develop a one-step immunoenzymometric assay which allows the quantification of both cardiac and skeletal isoforms (scTnI IEMA). The present report describes the main characteristics of this assay. By using multiple peptide synthesis methods, the localization of the epitopes recognized by the two MAbs on sTnI were determined. The capture and tracer MAbs of the scTnI IEMA were shown to recognize epitopes located within positions 121-127 and 160-167 in the sTnI sequence, respectively. The results of this epitopic analysis are discussed in light of the cross reaction of these two MAbs with cTnI.

Cardiac troponin I to diagnose percutaneous transluminal coronary angioplasty-related myocardial injury.

The purposes of the present study were to evaluate cardiac troponin 1 (cTnl) in the diagnosis of percutaneous transluminal coronary angioplasty (PTCA)-related myocardial injury in comparison with cardiac troponin T (cTnT) and creatine kinase (CK) MB mass concentration, and to investigate the frequency of myocardial injury, as indicated by myocardial protein release, after clinically symptomless side-branch occlusion (SBO) which may occur in the proximity of the attempted stenosis. The final study population comprised 80 patients undergoing elective, single vessel PTCA. Blood samples were drawn before, 6, 24 and 48 h after PTCA. cTnI, cTnT and CKMB mass baseline values were within the reference intervals in all patients (cTnI < 0.1 microgram/l, cTnT < 0.2 microgram/l, CKMB < 5 micrograms/l). Two patients presented with primary failure of PTCA, and visually successful PTCA was performed in all remaining patients. Seven patients (four with SBO) subsequently developed acute myocardial infarction (AMI). Symptomless SBO occurred in 16 patients. In controls (n = 55) there were no significant increases in cTnI, cTnT, or CKMB concentrations compared with baseline values, and all markers stayed within their reference intervals. In half the patients with symptomless SBO (n = 8) all markers were slightly to moderately increased, in two additional patients only CKMB was elevated (cTnI: 0.1-1.0 microgram/l; cTnT: 0.25-0.81 microgram/l and CKMB: 7.9-25.6 micrograms/l). In the majority of patients with primary failure or AMI we found pronounced increases in all tested markers (cTnI: 0.2-12.0 micrograms/l; cTnT: 0.44-12.10 micrograms/l; CKMB: 19.2-423.0 micrograms/l). The results of this study indicate that cTnI is comparably useful to cTnT or CKMB mass for diagnosing myocardial injury in PTCA patients. From our results a preference for one of the tested parameters cannot be clearly derived. Post-procedural cTnI, cTnT, and CKMB mass values are not higher than baseline values in uncomplicated cases, whereas AMI after PTCA leads to pronounced marker increases. SBO, even when symptomless, leads frequently (in about half the patients) to slight marker increases.

Release kinetics of serum cardiac troponin I in ischemic myocardial injury.

OBJECTIVES: The study was undertaken to evaluate the release kinetics of cardiac troponin I (cTn-I) in ischemic myocardial injury. DESIGN AND METHODS: The reference range for cTn-I was established by determination of cTn-I in sera and plasma obtained from 622 healthy volunteers (Group 1). cTn-I was compared to: (a) Creatine kinase (CK) MB mass and myoglobin in 12 patients with severe skeletal muscle damage (Group 2); (b) CK-MB activity in 48 patients with myocardial infarction (MI) receiving intravenous thrombolysis (Group 3) (in this group, an additional 43 patients with MI were analyzed separately to characterize cTn-I patterns in thrombolyzed and nonthrombolyzed populations): and in 44 patients with unstable angina (Group 4). RESULTS: In Groups 1 and 2, no positive results (> or = 0.1 microgram/L) were obtained. In Group 3, the time-courses of cTn-I were mostly monophasic in form. A pathologic increase occurred earlier in cTn-I than in CK-MB activity (p = 0.0002); the period with increased cTn-I was longer (p = 0.001), the overall sensitivity of cTn-I (93.9%) was higher than that of CK-MB activity (p = 0.00001). cTn-I was more sensitive at admission (p = 0.0004). In additional patients, the cTn-I peak occurred and cTn-I disappeared significantly later in nonthrombolyzed than in the thrombolyzed group. In Group 4, positive tests results were detected in 45% of patients for cTn-I, 16% for CK-MB activity, and 32% for CK-MB mass. CONCLUSIONS: The cTn-I assay appears to be ideally suited for the detection of ischemic myocardial injury in complex clinical situations because of its high specificity; cTn-I indicates myocardial tissue damage in patients with unstable angina and is superior to CK-MB activity and mass in this respect.

Cardiac troponin I in the diagnosis of myocardial injury and infarction.

We used a cardiospecific enzymoimmunometric assay to measure cardiac troponin I (cTnI) in samples serially drawn from 78 patients with acute myocardial infarction (AMI), 7 patients with unstable angina (Braunwald class III), 22 multi-traumatized patients, and in 30 athletes after eccentric exercise, as well as in 101 non-traumatic chest pain patients on admission to the emergency department. cTnI assay crossreactivity with crude human skeletal muscle homogenates was < 0.1%. cTnI could not be detected in athletes or multi-traumatized patients except for 2 trauma patients with myocardial damage. Increased cTnI concentrations were found in 6 of 7 patients with unstable angina at rest and in all AMI patients. After AMI, cTnI increased about 3.5 h (median) after the onset of chest pain, reached peak values parallel to CKMB, and stayed increased for at least 4 days. Cardiac troponin T (cTnT) increased and mostly peaked parallel to cTnI. cTnT sensitivity on the 7th day after AMI was significantly higher than that of cTnI. In contrast to cTnI, cTnT mostly showed a second, usually smaller, peak about day 4 after AMI. During the first 4 h after the onset of chest pain and before thrombolytic therapy the sensitivities of myoglobin (0.43) and CKMB mass (0.56) were significantly higher than those of both troponins (cTnI, 0.29; cTnT, 0.25). Areas under receiver operator characteristic curves indicated only moderate diagnostic accuracies of bio-chemical markers for early AMI diagnosis in non-traumatic chest pain patients that cTnI is a highly sensitive and specific marker for myocardial damage which is suitable for early and late diagnosis.

[Value of human cardiac troponin I determination in the diagnosis of acute myocardial infarction]. / Intérêt du dosage de la troponine I cardiaque humaine dans le diagnostic de l'infarctus aigu du myocarde.

Immunoenzymatic assay (IEMA) of human cardiac Troponin I (TnI c) was used in patients admitted to the coronary care unit with acute myocardial infarction (AMI). TnI c was detected in all patients with AMI. The detection of TnI c was earlier after the onset of pain (4.5 +/- 2.3 hours) than that of CKMB activity (6.3 +/- 3.6 hours), p = 0.003. The kinetics of TnI c are usually monophasic and parallel to that of CKMB activity. The peak value occurs 12.2 +/- 4.6 hours and 15.8 +/- 9.0 hours after the onset of pain in patients treated by thrombolysis. The TnI c disappears from the plasma between 5 and 9 days after the onset of pain, later than CKMB activity (p = 0.0001). In 49 patients admitted for AMI treated by thrombolysis, the comparative sensitivities of TnI c (threshold: 0.1 ng/ml) and of CKMB activity (threshold: 15 IU/l; CK > or = 100 Ul/l) were, at the first sampling on admission, 61% and 22% respectively (p = 0.0002) (average interval from onset of pain to first blood sampling: 3.4 +/- 1.3 hours). TnI c was not detected in the plasma of 145 normal subjects nor in any of the 6 patients with severe muscular trauma or rhabdomyolosis (specificity: 100%). This IEMA is a specific and a sensitive method of diagnosing acute and subacute myocardial infarction. It is ideal for the detection of myocardial necrosis in complex clinical situations when the usual enzymatic markers may be ineffective.

Cardiac troponin I release correlates with myocardial infarction size.

Cardiac troponin I, creatine kinase, and creatine kinase MB activity were tested in serial blood samples from 15 patients with first-time Q wave acute myocardial infarction (2 anterior and 13 inferior wall infarctions). All patients received intravenous thrombolytic therapy. Cardiac troponin I and creatine kinase MB activity were compared with scintigraphic estimates of myocardial scar (single photon emission computed tomography [SPECT] with 99mTechnetium-isonitrile [Tc-sestamibi]) on late images at rest about 5 weeks after myocardial infarction. Scintigraphic defect sizes ranged from 3.2 to 41.2% (median: 27.3%) of left ventricle. Cardiac troponin I increased and peaked in parallel with creatine kinase MB activity, and the peak values correlated with each other (r = 0.76, p = 0.002). Troponin I stayed increased for several days longer than creatine kinase and creatine kinase MB activity. It could be detected at least until the 4th day after admission. Significant correlation coefficients were found between 99mTc-isonitrile defect sizes and areas under cardiac troponin I curves (r = 0.53, p = 0.042) and between 99mTc-isonitrile defect sizes and cumulative creatine kinase MB activity release (r = 0.64, p = 0.01). Animal studies have already shown a very close correlation between histologic infarct size and SPECT 99mTc-isonitrile defect size. Therefore, our results indicate that cardiac troponin I release in patients with acute myocardial infarction is also correlated with infarct size.

Rapid adaptation to eccentric exercise-induced muscle damage.

This study examined eccentric exercise-induced muscle damage and rapid adaptation. Twenty-two male subjects performed 70 eccentric actions with the knee extensors. Group A (n = 11) and group B (n = 11) repeated the same exercise 4 and 13 days after the initial bout, respectively. Criterion measures included muscle soreness, muscle force generation (vertical jump height on a Kistler platform), and plasma levels of creatine kinase (CK), slow-twitch skeletal (cardiac beta-type) myosin heavy chains (MHC), and cardiac troponin I. Subjects were tested pre-exercise and up to day 4 following each bout. The initial exercise resulted in an increase in CK and MHC, a decrement in muscle force, and delayed onset muscle soreness in all participants. CK and MHC release correlated closely (rho = 0.73, p = 0.0001), both did not correlate with the decrement in muscle force generation after exercise. Because cardiac troponin I could not be detected in all samples, which excluded a protein release from the heart (cardiac beta-type MHC), this finding provides evidence for a injury of slow-twitch skeletal muscle fibers in response to eccentric contractions. Repetition of the initial eccentric exercise bout after 13 days (group B) did not cause muscle soreness, a decrement in muscle reaction force with vertical jump or significant changes in plasma MHC and CK concentrations, whereas in case of repetition after 4 days (group A) only the significant increases in CK and MHC were abolished. The decrement in reaction force with vertical jump did not differ significantly from that after the initial exercise session, but perceived muscle soreness was less pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)