[Diagnostic and prognostic significance of CK-MB, troponins, CRP, BNP and/or NT-proBNP in coronary angioplasty. Elevation mechanisms and clinical implications]. / Intérêt diagnostique et pronostique des marqueurs biologiques dans l'angioplastie coronaire en cas d'angor stable et de syndrome coronaire aigu ST-. Quelle stratégie biologique en routine?

The recommendations from respected bodies concerning the treatment and follow up of patients undergoing coronary angioplasty for stable angina or acute coronary syndrome (ACS) are essential for reducing the risks related to the procedure, and for preventing the occurrence of long term complications. Measuring the levels of troponin and CK-MB is part of the diagnostic and prognostic strategy during the coronary angioplasty procedure. In this context, the frequent elevation of markers following uncomplicated angioplasty is a sign of minor irreversible myocardial damage, the prognostic significance of which remains under discussion. Recent data suggest that only a basal troponin elevation (more so than CK-MB) prior to angioplasty has a long term prognostic value in ACS ST- patients, and that troponin elevation occurring after the procedure in the presence of normal basal concentrations, is only associated with in-hospital complications. Determining the basal level of troponin would appear to be essential for interpreting any elevation in concentrations following angioplasty. The recommendations should integrate this fundamental point, if it is confirmed. On the other hand, the question has been raised whether other markers (CRP, BNP and/or NT-proBNP) should be systematically measured as a routine prior to angioplasty. An elevation of CRP before and/or after angioplasty is an unfavourable short and long term prognostic factor. Elevation of NT-proBNP before angioplasty is also an unfavourable long term prognostic factor. Recommending a multi-marker strategy might represent a future direction for identifying at risk patients prior to coronary angioplasty, thus enabling specific treatment to be proposed.

Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders.

Some previous studies have reported the involvement of magnesium (Mg) deficiency in children with ADHD syndrome. In this work, 40 children with clinical symptoms of ADHD were followed clinically and biologically during a magnesium-vitamin B6 (Mg-B6) regimen (6 mg/kg/d Mg, 0.6 mg/kg/d vit-B6) which was set up for at least 8 weeks. Symptoms of ADHD (hyperactivity, hyperemotivity/ aggressiveness, lack of attention at school) were scored (0-4) at different times; in parallel, intraerythrocyte Mg2+ (Erc-Mg) and blood ionized Ca2+ (i-Ca) were measured. Children from the ADHD group showed significantly lower Erc-Mg values than control children (n = 36). In almost all cases of ADHD, Mg-B6 regimen for at least two months significantly modified the clinical symptoms of the disease: namely, hyperactivity and hyperemotivity/aggressiveness were reduced, school attention was improved. In parallel, the Mg-B6 regimen led to a significant increase in Erc-Mg values. When the Mg-B6 treatment was stopped, clinical symptoms of the disease reappeared in few weeks together with a decrease in Erc-Mg values. This study brings additional information about the therapeutic role of a Mg-B6 regimen in children with ADHD symptoms.

Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism.

Previous studies reported positive results with the use of Mg-vitamin B6 in autism. Despite these reports, this intervention remains controversial. In order to study relationships between changes in clinical symtoms and biological parameters, 33 children (mean age: 4 [1-10] years old) with clinical symptoms of pervasive developmental disorder or autism (PDD, as defined in DSM-IV) were followed for at least 6 months; another group of 36 children (same age) devoided of any known pathology was used as control. All PDD children received a magnesium-vit B6 (Mg-B6) regimen (6 mg/kg/d Mg and 0.6 mg/kg/d vit B6). Intraerythrocyte Mg2+ (Erc-Mg), serum Mg2+ (s-Mg) and blood ionized Ca2+ (i-Ca) were measured before and after treatment. Clinical symptoms of PDD were scored (0 to 4). In contrast to s-Mg or i-Ca, PDD children exhibited significantly lower Erc-Mg values than controls (2.17 +/- 0.4 versus 2.73 +/- 0.23 mmol/L; 16/33). The Mg-B6 regimen led to an increase in Erc-Mg values (2.42 +/- 0.41 (after) versus 2.17 +/- 0.4 mmol/l (before), 11/17) and this supplementation improved PDD symptoms in 23/33 children (p < 0.0001) with no adverse effects: social interactions (23/33), communication (24/33), stereotyped restricted behavior (18/33), and abnormal/delayed functioning (17/33); 15/33 children were improved in the first three groups of symptoms. When the Mg-B6 treatment was stopped, PDD symtoms reappeared in few weeks. A statistically significant relationship was found in Erc-Mg values from children before treatment and their mothers. In conclusion, this study suggests that the behavioral improvement observed with the combination vitamin B6-magnesium in PDD/autism is associated with concomitant modifications of Erc-Mg values.

[Three-dimensional echography: cardiovascular applications]. / Echographie tridimensionnelle: applications cardio-vasculaires.

Real-time three-dimensional echocardiography is currently used in a standard echocardiographic examination. Volume-rendered images better identify and locate anatomic structures and improve our comprehensive approach to various heart diseases. The assessment of mitral valve disease and congenital cardiopathies and the measurement of left ventricular mass, volume, and ejection fraction are the three main applications of three-dimensional echocardiography. Three-dimensional vascular imaging is an emerging and promising application of three-dimensional echography. The near future of three-dimensional echography requires the integration of all modalities of conventional echography in three dimensional probes, a higher image resolution compared to the current situation, as well as the development of real-time three-dimensional probes dedicated to transesophageal cardiac or vascular examination.

Ross procedure is a safe treatment option for aortic valve endocarditis: Long-term follow-up of 42 patients.

BACKGROUND: Aortic root replacement with a pulmonary autograft (Ross procedure) can be performed as a treatment of aortic valve endocarditis, avoiding prosthetic valve implantation in septic context. We sought to assess long-term outcomes of the Ross procedure in this indication. METHODS: From April 1992 to March 2009, the intervention was performed in 42 patients (mean age 34 ± 8 years) suffering from an active or ancient aortic valve endocarditis. 36% of the patients had extensive perivalvular involvement, and surgery was urgent in 18 patients (43%). We performed a prospective clinical and echocardiographic follow-up of this population. RESULTS: Median follow-up was 10 years (4-21 years). Overall survival at 10 and 15 years was respectively 87 ± 5% and 81 ± 8%. Perioperative mortality was 4.7% (2 patients) and no late cardiac death was reported. Eight patients (19%) underwent repeat surgery for autograft and/or homograft dysfunction at a median time of 8.4 years (3 months-18 years). Rate of recurrent endocarditis was low (7%-3 patients), including 1 in a context of persistent intravenous drug abuse. Clinical follow-up showed good functional status for all patients with NYHA ≤ II, and less than 25% of patients requiring cardiovascular medication. Late echocardiographic follow-up demonstrated well-functioning autograft and homograft, with only one severe aortic regurgitation, and one significant increase in pulmonary mean gradient. CONCLUSION: The Ross procedure in aortic valve endocarditis is an interesting alternative to prosthetic valvular replacement in a selected population, with a high rate of survival free from any cardiovascular event or medication requirement.

[Diagnostic and prognostic value of heart-type fatty acid-binding protein (H-FABP), an early biochemical marker of myocardial injury]. / Intérêt diagnostique et pronostique de H-FABP (heart-type fatty acid-binding protein ou protéine cardiaque liée aux acides gras), marqueur biochimique précoce de la souffrance myocardique.

Heart-type fatty acid-binding protein (H-FABP) is a 132 amino acids soluble protein, with general characteristics resembling myoglobin. Because of its low molecular weight (15 kd) and cytoplasmic location, it constitutes a biologic marker readily released into the circulation after myocardial injury. Despite the development of various immunoassays to measure H-FABP, few are currently easy to perform, quantitative and applicable in emergency. Most studies have shown the diagnostic sensitivity of H-FABP (i.e. its ability to detect the presence of a myocardial infarction) to be high, above that of myoglobin in patients presenting within 3 to 6 h of after the onset of chest pain. This superiority is attributable to an earlier and more rapid rise in H-FABP than in myoglobin. After thrombolysis, the serum concentrations of H-FABP peak at approximately 4 h after the onset of chest pain, and return to normal values within 24 h. Because of this rapid return of its blood concentration to baseline, H-FABP can contribute to an early biologic diagnosis of post-thrombolysis reperfusion and re-infarction. In absence of renal insufficiency, H-FABP also provides a reliable estimate of infarct size associated with ST segment elevation. When myocardial injury occurs after cardiac surgery, the second peak in H-FABP concentration precedes that of myoglobin, CK-MB or troponins. In addition, H-FABP peaks earlier and is more sensitive than troponins in the detection of subtle myocardial injury in patients presenting with acute coronary syndrome without ST segment elevation, and in patients with severe heart failure, thus offering early prognostic information. Limitations of H-FABP include a limited cardio-specificity, a narrow diagnostic window (20 to 30 h), and a nearly exclusive renal elimination.

Relation of minor cardiac troponin I elevation to late cardiac events after uncomplicated elective successful percutaneous transluminal coronary angioplasty for angina pectoris.

There is little information about the relation between mild cardiac troponin I (cTn-I) increase after coronary interventions and late outcome. We therefore focused on the long-term outcome and the clinical, morphologic, and procedural correlates of elevation of cTn-I compared with cardiac troponin T, creatine kinase (CK), CK-MB activity and mass, and myoglobin in 105 patients with successful elective percutaneous transluminal coronary angioplasty (PTCA) for stable or unstable angina. Patients with myocardial infarction and those with unstable angina who had a detectable increase in serum markers before PTCA were excluded. Markers were measured before and after the procedure and for 2 days. Patients were followed up to record recurrent angina, myocardial infarction, cardiac death, repeat PTCA, or elective coronary artery bypass graft surgery. Procedure success was achieved in all cases. Elevation in cTn-I (> or =0.1 microg/L) was observed in 23 of 105 patients (22%) (median peak: 0.25 microg/L); 18% had cardiac troponin T (cTn-T) release (> or = 0.1 microg/L, median peak 0.21); 11.4% CK-MB mass (> or =5 microg/L), and 7.6% myoglobin (> or =90 microg/L) release. Five and 2 patients had elevated CK and CK-MB activity, respectively. Fourteen of 18 patients with cTn-T elevation had a corresponding elevation in cTn-I (kappa 0.68; p = 0.001). Patients positive for cTn-I had more unstable angina (p = 0.042) and heparin before PTCA (p = 0.046), and had longest total time (p = 0.004) and single inflation (p = 0.01). By multivariate logistic regression, predictors of postprocedure cTnI elevation were maximum time of each inflation (odds ratio 9.2; p = 0.0012), type B lesions (odds ratio 6.6; p = 0.013), unstable angina (p = 0.041), and age > or =60 years (p = 0.032). Clinical follow-up was available in 103 patients (98%) (mean 19+/-10 months). Kaplan-Meier survival analysis showed that cTn-I elevation was not an important correlate of cardiac events (p = 0.34, by log-rank analysis). The incidence of recurrent angina, myocardial infarction, cardiac death, and repeat revascularization after 12 months was not different in patients positive or negative for cTn-I. We conclude that cTn-I elevation after successful PTCA is not associated with significantly worse late clinical outcome. Levels of cTn-I allow a much higher diagnostic accuracy in detecting minor myocardial injury after PTCA compared with other markers, but there is no association with periprocedural myocardial cell injury and late outcome when cTn-I and other markers are considered.

Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats.

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The highest cTnI (mean+/-S.D., 1.1+/-2.3 ng/ml) and cTnT (mean+/-S.D. 3.6+/-30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl and cTnT curves (AUC) (0-6 h) and the maximal cTnI and cTnT (0-6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered (P=0.08) and for LD AUC (0-6 h) (P=0. 059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.

Time-course of cardiac troponin I release from isolated perfused rat hearts during hypoxia/reoxygenation and ischemia/reperfusion.

The study was designed to determine the time-course of cardiac troponin I (cTn-I) release in isolated and Langendorff-perfused rat hearts during hypoxia and reoxygenation (H/Reox), and after various durations of total ischemia and subsequent reperfusion (I/R). For this purpose, in H/Reox, cTn-I was measured with the conventional Access immunoassay (ng/ml) and a new immunoassay which operates at pg/ml, and compared with creatine kinase (CK), lactate dehydrogenase (LD) and cardiac troponin T (cTn-T). In I/R, cTn-I was compared with CK and LD. The anti-Tn-I mAbs used in cTn-I assays cross-react with cTn-I of the rat. A clear difference between time-courses and concentration levels of cTn-I in I/R and H/Reox models was found. In I/R, maximum release of cTn-I, CK and LD similarly occurred within minutes following reperfusion; however cTn-I did not return to baseline values. cTn-I levels were not linked to the duration of ischemia. In I/R, we were only able to detect small cTn-I concentrations. In H/Reox experiments, cTn-I, CK and LD increased time-dependently. We found higher cTn-I maximal peak levels detected with the Access immunoassay than with the new assay (median, 0.346 ng/ml per min/g dry wt vs 132 pg/ml per min/g dry wt). cTn-T maximal concentrations were lower than maximal cTn-I levels (median, 0.117 ng/ml per min/g dry wt). Time-courses of cTn-I release were roughly similar with both assays in the H/Reox model (r = 0.90). These data indicate that the cTn-I time-course is related to experimental model (I/R or H/Reox), but also likely depends on the sensitivity of cTn-I assays in such experimental conditions.

Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings.

BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.

[Troponins: new biochemical markers of myocardial damage. Structure, immunoassay and clinical application]. / Troponines: nouveaux marqueurs biochimiques de la souffrance myocardique. Structure, immunodosages et applications cliniques.

The development of immunoassay techniques has made it possible to use new biochemical markers with a high myocardial specificity. Immunoassays have been developed for two of the structural myocardial proteins: troponin I and troponin T. The authors describe the biochemical properties of the troponins and the available methods of immunoassay. The main clinical applications of troponin measurement in cardiological practice are also reported.

[Prognostic significance of early raised cardiac troponine I in unstable angina. Contribution to the identification of a high-risk sub-group]. / Signification pronostique de l'élévation précoce de la troponine I cardiaque chez les patients en angor instable. Contribution à l'identification d'un sous-groupe à haut-risque.

The authors compared the clinical and angiographic characteristics of 44 patients with unstable angina according to cardiac Troponine I concentrations (TnIc) during early blood sampling and then tried to determine a threshold value to predic the occurrence of cardiac events during the hospital period and after 12 months. Tnlc, creatinine-kinase (CK), CK-MB activity and CK-MB mass were sampled over 48 hours. Forty-five per cent of patients had TnIc > or = 0.1 microgram/L; CK-MB activity and CK-MB mass were detected in 16 and 32% of patients. Age, gender, classification and recurrence of angina, previous cardiac history, risk factors, coronary angiographic appearances were comparable in patients with and without raised TnIc. No major cardiac events occurred during the hospital period in either group. The number of angioplasties and coronary bypass procedures was also comparable. At one year, the incidence of myocardial infarction (N = 4) and death (N = 5) was significantly different in patients with raised Tnlc (33% versus 0% in patients without increased TnIc). However, betablocker therapy was less prescribed in the group with the poorest outcomes and left ventricular dysfunction was also significantly more common in this group. Early elevation of Tnlc could contribute to the identification of a high risk subgroup of patients with unstable angina.

[Effect of the age and the sex on plasma concentration of amino acids]. / Effet de l'âge et du sexe sur les concentrations des acides aminés plasmatiques.

The effects of age and sex on the plasma free amino acid pattern of healthy men and women aged from 80 to 100 years were compared with those in younger adults (20 to 45 years old). Plasma amino acid concentrations were determined by ion-exchange chromatography on a 6300 Beckman analyzer. The plasma concentrations of valine, leucine, isoleucine, proline, glutamine + glutamic acid and phenylalanine were higher in males than in females. Citrulline, half-cystine, histidine, glutamine+glutamic acid, lysine, ornithine and phenylalanine plasma concentrations and the total plasma amino acids were higher in elderly than in younger subjects.

Could B-type Natriuretic Peptide (BNP) plasma concentration be useful to predict fluid responsiveness [corrected] in critically ill patients with acute circulatory failure?

BACKGROUND AND OBJECTIVES: As B-type Natriuretic Peptide (BNP) is a marker of ventricular wall stress, the present study was aimed at determining whether plasma BNP concentration could predict fluid responsiveness in critically ill patients with acute circulatory failure. METHODS: This prospective and non randomized interventional study included 33 sedated, mechanically ventilated patients, with acute circulatory failure requiring cardiac output measurement and fluid challenge. Plasma BNP concentration was measured before and after fluid challenge (250 to 500 ml with infusion rate=999 ml/h). An increase in stroke index (SI) greater than or equal to 15% allowed separation of responders from nonresponders. Receiver operating characteristic (ROC) curves were generated for BNP and compared to that of central venous pressure (CVP) that is routinely considered as a marker of cardiac preload. RESULTS: Among 33 patients, there were 24 responders. At baseline, BNP plasma values were less in responders (328 [35-1190] pg/ml versus 535 [223-5000] pg/ml, p<0.03). The area under the ROC curves was 0.74+/-0.11, that was similar to the area under the ROC curve for CVP (0.77+/-0.10). The best cut-off value of plasma BNP level for predicting fluid responsiveness was 193 pg/ml (sensitivity: 38%, specificity: 100%, positive predictive value: 100%, negative predictive value: 38%, accuracy: 55%). Fluid challenge did not increase plasma BNP concentrations in responders and nonresponders. CONCLUSION: In critically ill patients with acute circulatory failure, BNP does not accurately predict fluid responsiveness.

Plasma amino acid concentrations in elderly patients with protein energy malnutrition.

OBJECTIVE: to compare amino acid concentrations in healthy and malnourished elderly patients. METHOD: plasma amino acid concentrations were examined in 24 men and women (80-100 years of age) with protein energy malnutrition (PEM) and compared with those of 44 healthy, similarly-aged controls. Plasma samples were determined by using cation exchange columns with ninhydrin detection in an high performance liquid chromatography system. RESULTS: essential amino acid and non-essential amino acid plasma concentrations were significantly decreased in PEM (0.01 < P < 0.0001). Branched-chain amino acids and urea cycle amino acid plasma concentrations fell significantly (P < 0.0001). Plasma concentrations of alanine and glutamic acid + glutamine were also significantly reduced (P < 0.0001). CONCLUSIONS: in underweight elderly patients, the plasma amino acid pattern reflects the severity of the metabolic disturbance.

Mechanisms of ventricular arrhythmias induced by myocardial contusion: a high-resolution mapping study in left ventricular rabbit heart.

BACKGROUND: The aims of the Langendorff-perfused rabbit heart study were to evaluate the arrhythmogenic consequences of myocardial contusion and to determine the mechanism of arrhythmia. METHODS: Six hearts were in the control group, and 24 hearts (intact heart protocol) were submitted to one of four different contusion kinetic energies (75, 100, 150, or 200 millijoules [mJ]; n = 6). Occurrence of arrhythmia, of an electrically silent area (i.e., area with no electrical activity), and of line of fixed conduction block were reported before and for 1 h after contusion. In 16 hearts (frozen hearts) submitted to cryoprocedure and contusion impact of 100 or 200 mJ, ventricular conduction velocities, anisotropic ratio, wavelengths, ventricular effective refractory period, and its dispersion were measured before and for 1 h after contusion. Using high-resolution mapping, arrhythmias were recorded and analyzed. RESULTS: The intact heart study showed that the number and seriousness of contusion-induced arrhythmias increased with increasing contusion kinetic energy, as did the number of electrically silent areas (five of six ventricular fibrillations and five of six electrically silent areas at 200 mJ). In the frozen heart study, immediately after contusion ventricular effective refractory periods were shortened and dispersed, and wavelengths were also shortened. The arrhythmia analysis showed that all ventricular tachycardias but one were based on reentry developed around an electrically silent area or a line of fixed conduction block. CONCLUSIONS: Myocardial contusion has direct arrhythmogenic effects, and the seriousness of arrhythmia increases with the level of contusion kinetic energy. The mechanism of arrhythmia was mainly based on reentrant circuit around a fixed obstacle.

p53 and follow-up of colorectal adenocarcinomas.

Circulating p53 antibodies (ELISA method), p53 genetic alterations (SSCP), and protein overexpression (immunohistochemistry) were studied in 41 patients with colorectal adenocarcinomas and 10 control patients. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19-9) were evaluated in parallel. Ten patients with p53 antibodies and p53 overexpression were selected. Tumor DNA extracts from these 10 patients were analyzed by SSCP. Of all 41 patients, 10 (24%) showed significant levels of p53 antibodies, and p53 accumulation was detected in 20 (48%) patients. In six patients, p53 antibody concentrations decreased rapidly after surgery; in two patients, these levels returned to normal values. Of the 10 selected tumors, eight revealed TP53 gene mutations. Only two patients with high values of both CEA and CA 19-9 developed p53 antibodies. In conclusion, beside classical tumor markers, circulating p53 antibodies may be considered as additional markers for the management of patients with colorectal adenocarcinomas.

Neurohormonal stimulation of histamine release from neuroendocrine cells of the human adenomatous prostate.

BACKGROUND: Neuroendocrine cells (NE) constitute a population of highly specialized cells in prostatic glands; histamine has never been described in these cells. This article shows the presence and the regulation of release of histamine in NE. METHODS: In 21 prostatic adenomas, NE were identified by specific antisera against neuroendocrine markers (chromogranin-A, synaptophysin), histamine, and histidine decarboxylase (HDC); a rate HDC-cDNA probe was used to detect this enzyme by in situ hybridization. RESULTS: Immunoreactive cells for chromogranin-A, histamine, and HDC were found among luminal epithelial glandular cells. Similar cells were also labeled with the HDC-cDNA probe. Glandular cells, isolated from prostatic adenomas, were shown to contain histamine (7-40 pmol/mg cellular protein). L(-) norepinephrine causes a time-dependent (t1/2 = 22 min) histamine release; the alpha 1-receptor antagonists WB-4101 and YM-617 specifically inhibited this release, in agreement with a mediation by alpha 1-adrenoreceptor subtype. CONCLUSIONS: There is some evidence for the presence in prostatic adenomas of histamine-forming cells of neuroendocrine type; histamine release from these cells is under the control of alpha 1-adrenoreceptor subtype.

CK-MB mass test in ischemic myocardial injury. Comparison of two tests: BioMerieux Vidas and sanofi access immunoassays.

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.

Release kinetics of cardiac troponin I and cardiac troponin T in effluents from isolated perfused rabbit hearts after graded experimental myocardial contusion.

BACKGROUND: Few experimental studies report effects of direct contusion on cardiac enzyme release. Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. This investigation was designed to determine and compare the acute effects of quantified magnitudes of blunt cardiac trauma upon release of cTnI and cTnT in comparison with creatine kinase (CK) and lactate dehydrogenase (LD). METHODS: In 24 rabbit hearts prepared on a standard Langendorff apparatus, myocardial contusion (MC) was produced by a single blow with a ball falling from a predefined height, delivered directly to the surface of the heart. Hearts were divided into control (n = 6) and various quantified impacts: 75 mJoules (mJ) (n = 6), 100 mJ (n = 6), 200 mJ (n = 6). Coronary effluent samples for cTnI, cTnT, CK, and LD were collected at baseline, immediately after MC and 5, 15, 30, 45, and 60 minutes after MC. At the end of experiment, histologic condition was evaluated. RESULTS: The anti-cTnI and cTnT MAbs used in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rabbit. The time-courses of cTnI, cTnT, CK, and LD were monophasic in form. After MC, all parameters rose significantly compared with baseline and with control group. The maximal release occurred immediately after MC. The area under the cTnI curve and the maximal cTnI concentration were linked to the contusion energy when increased at 200 mJ. Maximal concentrations and areas under cTnT, CK, LD time activity curve were not linked to the contusion energy level and showed no between-energy group differences. The correlation found between maximal cTnI and maximal cTnT concentrations was 0.70 (p = 0.0001). Histologic examination showed cellular disruption and after the more severe impact, the extent of pathologic changes was more extensive. CONCLUSION: After graded experimental MC, maximal cTnI concentration and area under cTnI curve increase with the power of impact kinetic energy. Levels of cTnI allow a much higher accuracy in detecting the extent of myocardial injury postMC in comparison with cTnT, CK, and LD in this experimental study. These results should be consistent with the more extensive cTnI release with more severe impact in patients with blunt chest trauma. Furthermore, because specificity and time-course of release, both cTnI and cTnT should have a role in the diagnosis and evaluation of such patients.