Assessment of peak skin dose in interventional cardiology: A comparison between Gafchromic film and dosimetric software em.dose.

OBJECTIVE: To compare the use of a dose mapping software to Gafchromic film measurement for a simplified peak skin dose (PSD) estimation in interventional cardiology procedure. METHODS: The study was conducted on a total of 40 cardiac procedures (20 complex coronary angioplasty of chronic total occlusion (CTO) and 20 coronary angiography and coronary angioplasty (CA-PTCA)) conducted between January 2014 to December 2015. PSD measurement (PSDFilm) was obtained by placing XR-RV3 Gafchromic under the patient's back for each procedure. PSD (PSDem.dose) was computed with the software em.dose©. The calculation was performed on the dose metrics collected from the private dose report of each procedure. Two calculation methods (method A: fluoroscopic kerma equally spread on cine acquisition and B: fluoroscopic kerma is added to one air Kerma cine acquisition that contributes to the PSD) were used to calculate the fluoroscopic dose contribution as fluoroscopic data were not recorded in our interventional room. Statistical analyses were carried out to compare PSDFilm and PSDem.dose. RESULTS: The PSDFilm median (1st quartile; 3rd quartile) was 0.251(0.190;0.336)Gy for CA-PTCA and 1.453(0.767;2.011)Gy for CTO. For method-A, the PSDem.dose was 0.248(0.182;0.369)Gy for CA-PTCA and 1.601(0.892;2.178)Gy for CTO, and 0.267(0.223;0.446)Gy and 1.75 (0.912;2.584)Gy for method-B, respectively. For the two methods, the correlation between PSDFilm and PSDem.dose was strong. For all cardiology procedures investigated, the mean deviation between PSDFilm and PSDem.dose was 3.4±21.1% for method-A and 17.3%±23.9% for method-B. CONCLUSION: The dose mapping software is convenient to calculate peak skin dose in interventional cardiology.

Assessment of Patient's Peak Skin Dose Using Gafchromic Films During Interventional Cardiology Procedures: Routine Experience Feedback.

To assess the interest of Gafchromic films in detection of patient's peak skin dose (PSD) in interventional cardiology. A prospective study of 112 patients was conducted (July-December 2015). Three diagnostic and therapeutic procedures were evaluated: coronary angiography (CA), coronary angiography and coronary angioplasty for one or two vessels disease (CA-PTCA) and coronary angioplasty of complex chronic total occlusion (CTO). Dosimetric indicators (DIs) were collected and PSD were measured with Gafchromic films. Dose distribution was evaluated within 10 'Thorax Body-zone' defined by the system. Correlations between PSD and DI or dose distribution were computed. Delivered dose increased in complex procedures. The PSD were 0.121 ± 0.063 Gy for CA, 0.256 ± 0.142 Gy for CA-PTCA and 1.116 ± 0.721 Gy for CTO. High correlations were observed for PSD and DI as well for dose distribution within the 'Thorax Body-zone'. Film dosimetry is suggested for CTO procedures since the threshold of 2 Gy for skin injuries is likely to be exceeded.

Impact of the calibration conditions of XR-RV3 films on peak skin dose measurements in interventional radiology.

In this study, the impact of radiochromic films' (XR-RV3) calibration on PSD measurements was investigated under various peak kilovoltage (kVp) and additional filtration conditions. Films were calibrated free-in-air for six beam qualities with Allura Xper FD20 system (Philips). Six calibration curves (CCs) were constructed. Each beam quality was characterized in terms of mean energy (ME) in the air, with table, with table and water phantom using Monte Carlo simulations. A cohort of 155 patient films from cardiology (37) and vascular (118) procedures were read with each CC. Routine calibration beam quality was taken as reference (DoseNorm). Overall, it was observed that for a wider ME difference between the exposed film and the CC used, a larger deviation (from -28% to +41%) was observed. The choice of beam quality for the calibration is a key point when additional filtration and kVp are automatically controlled in clinical conditions.

[What is the place of bioresorbable vascular scaffolds in setting of ST-segment elevation myocardial infarction?]. / Quelle place pour les stents biorésorbables dans la prise en charge du syndrome coronarien aigu avec sus-décalage du segment ST ?

A 50-year-old woman was admitted for an inferior ST-segment elevation myocardial infarction; immediate coronary angiogram revealed a subocclusive stenosis of the right coronary artery. After optimal antithrombotic treatment, the type of stent could be discussed. The latest generation of drug-eluting stents showed excellent efficacy and safety in the long-term but has limitations such as potential chronic inflammation of the arterial wall and no recovery of vasoactive function. Bioresorbable vascular scaffolds, with complete resorption within several months, may reduce these limitations. Implantation of bioresorbable scaffold in the context of myocardial infarction may be interesting. However, very few studies are currently available in this setting. Preliminary results and perspectives are presented in this review.

[Are there any contraindications to the transradial approach?]. / Existe-t-il des contre-indications à la coronarographie par voie radiale ?

The transradial approach is the most frequent access used in France for coronarography and percutaneous coronary intervention. This access permits a reduction of local complications in comparison with femoral access. There are very few real contraindications of transradial approach. The use of Allen's test before coronarography remains controversial in the transradial catheterization community. It remains a standard practice in some institutions, however many centers have stopped using Allen's test considering that there is no evidence supporting its use.

[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.

High versus low training frequency in cardiac rehabilitation using a systems model of training.

No study has reported the long term effects of cardiac rehabilitation, concerning the duration of beneficial effects of training program. The present study analyzed the influence of training session frequency on long-term beneficial effects in patients with coronary artery disease (CAD) undergoing phase 2 cardiac rehabilitation. Four patients with CAD completed 20 training sessions. Two patients were assigned to low training frequency (LTF) and two to high training frequency (HTF): three and five sessions per week(-1), respectively. The method was based on the systems model of training and required training quantification and the assessment of real exercise tolerance. Convolution of training quantity with real exercise tolerance provided the model exercise tolerance for every patient. The model parameters, the magnitude factor (k), and the time constant of decay (tau), were fitted from real and model exercise tolerances by the least squares method. LTF and HTF resulted in similar increases in exercise tolerance (12-14%). A model with one-component (fitness) allowed fitting exercise tolerance in all patients with r (2) = 0.77, 0.79, 0.84, and 0.91, respectively (p < 0.05). The addition of a second component did not improve the fit in any patient (p > 0.05). The k value was about twice as high with LTF (0.13 and 0.16 AU) than with HTF (0.05 AU for the two patients), whereas the tau value was about twice as low with LTF (37 and 41 days) than with HTF (72 and 89 days). The long term beneficial effects estimated by 4tau, were twice as long with HTF (288 and 356 days) than with LTF (148 and 164 days). We concluded that exercise tolerance was similarly increased with HTF and LTF but HTF training induced beneficial effects which were sustained twice as long.

[Strength training with elastic bands: measure of its effects in cardiac rehabilitation after coronary diseases]. / Le renforcement musculaire par bandes élastiques : évaluation de ses effets dans le réentraînement à l'effort du coronarien.

OBJECTIVES: To compare high intensity strength training with weightlifting exercises or with elastic bands. SETTING: Outpatient unit of cardiac rehabilitation. TYPE: Prospective randomised clinical trial. POPULATION: Inclusion of coronary patients in phase II after medical or surgical treatment of a myocardiac infarction, without cardiac insufficiency; beta-blockers were accepted. METHOD: Evaluation of coronary patients at beginning and at the end of a 4 week cardiac rehabilitation program. It included progressive aerobic training according to Karvonen method for all the patients, associated with weightlifting exercises (Koch press) in the control group, or use of elastic bands in the experimental group. Cardiac rate, oxygen consumption at rest and at maximum power were the main criteria with also muscle strength of quadriceps, hamstrings, biceps brachii, latissimus dorsi and triceps brachii, body mass indexes, quality of life with SF-36, anxiety (stay T test) and perceived exertion with the Borg 10-point category-ratio scale, myotendinous injuries (Shaw scale). RESULTS: Twenty-six coronary patients, all male from 45 to 65 years old, all receiving beta-blockers, were included, 13 in each group. Control and experimental groups were initially similar. At the end of the 4 week program, all the two groups improved significantly their strength and power and there were no differences between the two groups. Perceived exertion was lower in the group using elastic bands and there were no myotendinous lesions. CONCLUSION: Strength training with elastic bands is a low-cost, attractive, playful technique, proposed to a group of coronary patients, which appears as effective in cardiac rehabilitation as individual weightlifting training.

[Is it necessary to rehabilitate coronary artery disease patients based on ventilatory threshold?]. / Faut-il rééduquer les coronariens au seuil ventilatoire ?

PURPOSE: To compare the efficiency of two programs of exercise-based rehabilitation that are different for heart rate (HR) training in patients with coronary artery disease: heart rate (HR) according to Karvonen formula (HR training =70% (max HR -rest HR) +rest HR) or HR recorded at the gas exchange ventilatory threshold (VT). TYPE: Controlled randomised clinical trial. SETTING: Cardiovascular rehabilitation unit. METHOD: Twenty-four male patients (54 +/-9.5 years old) with coronary artery disease were allocated at random to one of the two groups: KHR group (n =13) according to Karvonen formula (n =11), and VTHR group according to VT determined by exertion test (n =13). The exercised-based program was similar for all the patients, differing only in HR training (five daily sessions a week for four weeks). Assessment tests were performed at D1 and D28 and included: - an exercise test with measure of HR and double product (HR x blood pressure) at rest, submaximal and maximal intensity, with measure of oxygen consumption and gas exchanges at rest and at maximum exercise; - specific functional tests based on daily life activities; - dyspnea assessment at maximal intensity; - quality of life measurement by SF36. It was taken notice of the drugs taken by the patients, specially betablockers. RESULTS: At inclusion, the two groups were not different for parametric (age, body mass index) and non parametric values (medical or surgical treatment, comorbidity). Even though HR training was significantly different (p <10(-6)), at the end of the program there was a significant increase of power and oxygen consumption at VT (+42.6%, p <10(-6); +18.6%, p <10(-5)) and at maximal intensity (+18.7 %, p <10(-6); 14.2 %, p <10(-5)), but differences between the two groups were not significant; double product was significantly lower at rest (-13.9 %, p <10(-5)) and at submaximal exertion (-10.6 %, p < 10(-3)). Yet, the two groups differed in HR, and HR increased in VTHR group and decreased in KHR, the difference being significant at VT (p =0.05), at submaximal (p =0.037) and maximal exercise (p = 0.05). Dyspnea at maximal intensity was higher in VTHR but SF36 values were not different. DISCUSSION AND CONCLUSION: These results confirm the efficiency of cardiac training program according to Karvonen formula as to ventilatory threshold. However, there is a negative chronotropic effect of cardiac training according to Karvonen formula with a higher intensity, which corresponds to a less cardiac work for a same activity.

Islet-brain1/JNK-interacting protein-1 is required for early embryogenesis in mice.

Islet-brain1/JNK-interacting protein-1 (IB1/JIP-1) is a scaffold protein that organizes the JNK, MKK7, and MLK1 to allow signaling specificity. Targeted disruption of the gene MAPK8IP1 encoding IB1/JIP-1 in mice led to embryonic death prior to blastocyst implantation. In culture, no IB1/JIP-1(-/-) embryos were identified indicating that accelerated cell death occurred during the first cell cycles. IB1/JIP-1 expression was detected in unfertilized oocytes, in spermatozoa, and in different stages of embryo development. Thus, despite the maternal and paternal transmission of the IB1/JIP-1 protein, early transcription of the MAPK8IP1 gene is required for the survival of the fertilized oocytes.

Trophoblast cell-specific carcinoembryonic antigen cell adhesion molecule 9 is not required for placental development or a positive outcome of allotypic pregnancies.

The carcinoembryonic antigen (CEA) family consists of a large group of evolutionarily divergent glycoproteins. The secreted pregnancy-specific glycoproteins constitute a subgroup within the CEA family. They are predominantly expressed in trophoblast cells throughout placental development and are essential for a positive outcome of pregnancy, possibly by protecting the semiallotypic fetus from the maternal immune system. The murine CEA gene family member CEA cell adhesion molecule 9 (Ceacam9) also exhibits a trophoblast-specific expression pattern. However, its mRNA is found only in certain populations of trophoblast giant cells during early stages of placental development. It is exceptionally well conserved in the rat (over 90% identity on the amino acid level) but is absent from humans. To determine its role during murine development, Ceacam9 was inactivated by homologous recombination. Ceacam9(-/-) mice on both BALB/c and 129/Sv backgrounds developed indistinguishably from heterozygous or wild-type littermates with respect to sex ratio, weight gain, and fertility. Furthermore, the placental morphology and the expression pattern of trophoblast marker genes in the placentae of Ceacam9(-/-) females exhibited no differences. Both backcross analyses and transfer of BALB/c Ceacam9(-/-) blastocysts into pseudopregnant C57BL/6 foster mothers indicated that Ceacam9 is not needed for the protection of the embryo in a semiallogeneic or allogeneic situation. Taken together, Ceacam9 is dispensable for murine placental and embryonic development despite being highly conserved within rodents.

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.

Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6.

Because ribosome biogenesis plays an essential role in cell proliferation, control mechanisms may have evolved to recognize lesions in this critical anabolic process. To test this possibility, we conditionally deleted the gene encoding 40S ribosomal protein S6 in the liver of adult mice. Unexpectedly, livers from fasted animals deficient in S6 grew in response to nutrients even though biogenesis of 40S ribosomes was abolished. However, liver cells failed to proliferate or induce cyclin E expression after partial hepatectomy, despite formation of active cyclin D-CDK4 complexes. These results imply that abrogation of 40S ribosome biogenesis may induce a checkpoint control that prevents cell cycle progression.

Evaluation of incidence, clinical significance, and prognostic value of circulating cardiac troponin I and T elevation in hemodynamically stable patients with suspected myocardial contusion after blunt chest trauma.

BACKGROUND: The frequency and prognostic influence of myocardial injury in patients with blunt chest trauma is controversial. We investigated the value of cardiac troponin I (cTn-I) and cardiac troponin T (cTn-T), highly specific markers of myocardial injury, to determine whether their measurement would improve the ability to detect myocardial contusion in stable patients with blunt chest trauma in comparison with conventional markers and whether they were associated with significantly worse late clinical outcome. METHODS AND RESULTS: Over an 18-month period, myocardial contusion was diagnosed in 26 of 94 patients (27.6%) with acute blunt chest trauma (motor vehicle crash; 81%), because of echocardiographic abnormalities (n = 12), electrocardiographic abnormalities (n = 29), or both. Patients with myocardial contusion had a significantly higher Injury Severity Score at the time of admission (p = 0.001) and a significantly longer hospital stay (p = 0.0008). All patients survived admission to hospital and were hemodynamically stable. None of the patients died or had severe in-hospital cardiac complications. The percentage of patients with elevated CK, (CK-MB/total CK) ratio, or CK-MB mass concentration was not significantly different between patients with or without myocardial contusion. However, there were significant differences between the two groups when we applied the commonly used threshold levels of CK-MB activity and myoglobin. The percentage of patients with elevated circulating cTn-I and cTn-T (> or = 0.1 microg/L) was significantly higher in patients with myocardial contusion (23% vs. 3%; p = 0.01 and 12% vs. 0%; p = 0.03, respectively). Complete changes in cTn-I and cTn-T correlated well (r = 0.91, p = 0.0001). Sensitivity, specificity, and negative and positive predictive values of cTn-I and cTn-T in predicting a myocardial contusion in blunt trauma patients were 23%, 97%, and 77%, 75%, and 12%, 100%, and 74%, 100%, respectively. Clinical follow-up was available in 83 patients (88%) (mean, 16 +/- 7.5 months). There were no deaths in either group directly attributed to cardiac complications. None of the patients had any long-term cardiac complications or myocardial failure related to blunt chest trauma. CONCLUSION: Although improved specificity of cTn-I and cTn-T compared with conventional markers, it should be emphasized that the main problem with cTn-I and cTn-T is low sensitivity as well as low predictive values in diagnosing myocardial contusion. cTn-I and cTn-T measurement is currently not an improved method in diagnosing blunt cardiac injury in hemodynamically stable patients. Moreover, there was no association of postmyocardial contusion cell injury and late outcome in these patients when cTn-I and cTn-T and other conventional markers were considered.

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.

Embryonic stem cells and gene targeting.

The development of gene targeting technology, the exchange of an endogenous allele of a target gene for a mutated copy via homologous recombination, and the application of this technique to murine embryonic stem cells has made it possible to alter the germ-line of mice in a predetermined way. Gene targeting has enabled researchers to generate mouse strains with defined mutations in their genome allowing the analysis of gene function in vivo. This review presents the essential tools and methodologies used for gene targeting that have been developed over the past decade. Special emphasis has been laid on the available embryonic stem cell lines and the importance of the genetic background. Also, the state-of-the art of gene targeting approaches in species other than mice will be discussed.

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.

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.

Differences between IL-4- and IL-4 receptor alpha-deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling.

IL-4 receptor alpha-chain-deficient (IL-4Ralpha-/-) mice were generated by homologous and site-specific recombination, using the Cre/loxP system in BALB/c-derived embryonic stem cells. In vitro analysis of cells from these mice revealed impaired IL-4- and IL-13-mediated functions, demonstrating that the IL-4Ralpha-chain is an essential component of both the IL-4 and the IL-13 receptor. Whereas Leishmania major-infected BALB/c mice developed fatal progressive disease with type 2 Ab responses within 3 mo, both IL-4Ralpha-/- and IL-4-/- BALB/c mice contained infection with reduced footpad swelling, parasite load, moderate histopathology, and type 1 Ab responses during this time period. Conclusively, these results demonstrate an IL-4-dependent mechanism of susceptibility in BALB/c mice. Nevertheless, in contrast to mutant mice, infected C57BL/6 mice healed completely within 3 mo, indicating that additional factors are necessary for subsequent healing and elimination of the pathogen. During the further course of infection, IL-4Ralpha-/- mice developed progressive disease with massive footpad swelling. Lesions became ulcerative and necrotic with subsequent destruction of connective tissue and bones, as well as dissemination into organs and consequent mortality within the monitored 6 mo of chronic infection. In striking contrast, IL-4-/- mice maintained control of infection on a moderate level, but were unable to clear the pathogen. The distinct phenotypes of the BALB/c embryonic stem cell-derived IL-4-/- and IL-4Ralpha-/- mouse strains identify previously unsuspected mechanisms for maintaining host immunity to chronic infection with L. major, mediated by a functional IL-13 receptor.